1

2

3

4 The functional genetic architecture of egg-laying and live-bearing

5 reproduction

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7

8 H. Recknagel1, M. Carruthers1,3, A. Yurchenko1,4, M. Nokhbatolfoghahai1, N. A. Kamenos2,

9 M.M. Bain1, K.R. Elmer1*.

10

11 Affiliations:

12 1Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical,

13 Veterinary & Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.

14 2School of Geographical and Earth Sciences, University of Glasgow, Glasgow, G12 8QQ,

15 UK.

16 3current address: School of Biological Sciences, University of Bristol, Bristol, UK.

17 4current address: Inserm U981, Gustave Roussy Cancer Campus, Université Paris Saclay,

18 Villejuif, France.

19 20 Abstract:

21 All amniotes reproduce either by egg-laying (oviparity), which is ancestral to vertebrates, or

22 by live-bearing (viviparity), which has evolved many times independently. However, the

23 genetic basis of these parity modes has never been resolved and consequently the homology

24 across evolutionary scales is currently unknown. Here we describe the functional genes and

25 genetic architecture of parity mode and its key traits, eggshell and gestation length, by

26 leveraging natural hybridisations between oviparous and viviparous lizards, and comparing

27 our findings across vertebrates. In lizards, parity trait genes were associated with

28 progesterone-binding functions and enriched for tissue remodelling and immune system

29 pathways. Viviparity involved more genes and complex gene networks than did oviparity.

30 Angiogenesis, vascular endothelial growth, and adrenoreceptor pathways were enriched in

31 the viviparous female reproductive tissue, while pathways for transforming growth factor

32 were enriched in the oviparous. Natural selection on these parity mode genes was evident

33 genome-wide. Our analysis of seven independent origins of viviparity in mammals,

34 squamates and fish, showed that genes active in pregnancy related to immunity, tissue

35 remodelling, and blood vessel generation. Therefore, our results demonstrate that pre-

36 established regulatory networks are repeatedly recruited for viviparity and that these are

37 shared at deep evolutionary scales.

38

2 39 Whether offspring hatch from calcified eggs (oviparity) or emerge from the mother via live

40 birth (viviparity) is a fundamental and dichotomous reproductive strategy with wide-ranging

41 consequences for animal ecology, development, physiology and evolution1. The difference

42 between these parity modes is complex; however, major transitions from oviparity to

43 viviparity evolved repeatedly across amniotes. All birds, most reptiles and a few mammals

44 retain the ancestral state of oviparity, while nearly all mammals and ~20% of reptiles are

45 viviparous. Mammals transitioned to viviparity once, while squamate reptiles have

46 independently transitioned perhaps more than 100 times1,2. Nonetheless, the reproductive

47 physiology, neuroendocrine, and developmental pathways regulating viviparous

48 reproduction are thought to be highly analogous among amniotes3–7. Gathering evidence to

49 test this hypothesis has been impeded by the deep evolutionary divergences between

50 oviparous–viviparous sister taxa, which obscure inference and preclude crossing experiments.

51 Consequently, the genetic bases of the parity modes have not been resolved for any

52 animal3,4,8.

53 Major adjustments to embryo development are necessary for the transition from

54 oviparity to viviparity including i) an increase in the internal gestation time, to the point

55 where the embryo is fully developed prior to parturition, and ii) the loss of a calcified

56 eggshell9. Simultaneously, changes are necessary for the mother and for the healthy

57 development of the embryo3,4, such as an active physiological exchange of gas, water and

58 calcium and an adjusted immune response for maternal–foetal communication4,10, which is

59 facilitated by uterine angiogenesis and membrane vascularisation3,4. To prevent abortion, the

60 mother’s immune response is suppressed, for example, via the down-regulation of pro-

61 inflammatory cytokines4. These developmental and physiological changes necessitate

62 coordinated integration, making the transition a step change; intermediate phenotypes are

63 considered a fitness valley, and most species are fixed for oviparity or viviparity11.

3 64 Here, we identify the functional genomic architecture of alterative parity modes—

65 oviparity and viviparity—using an exceptional natural model. The Eurasian common lizard

66 (Zootoca vivipara) is viviparous across the majority of its distribution; however, some

67 southern populations are oviparous. In this reproductively bimodal species, alternative parity

68 modes are genetically fixed but can interbreed12,13. These lizards are therefore uniquely

69 informative to definitively genetically map the bases of the parity modes, demonstrate the

70 functional genetic mechanisms and targets of natural selection and thereby infer the

71 molecular underpinnings of the egg-laying and live-bearing reproduction modes.

72

73 Egg-laying and live-bearing lizards hybridise

74 We intensively sampled a contact zone between oviparous and viviparous common lizards

75 with a divergence time of ~4 Mya14 where hybridisation had been speculated13,15. We

76 quantified the parity mode traits for pregnant females and their clutches (N = 606) (Extended

77 Data Fig. 1): i) embryonic stage at oviposition/parturition, ii) number of days a clutch was

78 externally incubated, iii) calcium content (% Ca) within eggshells/membranes and iv)

79 eggshell/membrane thickness. In addition, we genotyped adults (ddRADSeq12), resulting in

80 80,696 genome-mapped16 polymorphic loci (N = 831, including the phenotyped females).

81 As expected, oviparous and viviparous clutches differed substantially. Eggs from

82 oviparous females had a thick shell (49.8 ± 0.8 μm) covered with a dense layer of calcium

83 crystals (25.4 ± 1.3% Ca), encircling embryos laid at an early developmental stage (stage

84 31.1 ± 0.1) requiring extended external incubation (35 ± 0.2 days) (Figs. 1A–1D) before they

85 hatched at full development (stage 41). Conversely, offspring from viviparous females were

86 delivered fully developed (stage 41), surrounded by a thin uncalcified membrane (4.2 ± 0.1

4 87 μm; 1.6 ± 0.6% Ca), which they emerged from within a short time (1.9 ± 0.1 days) (Figs. 1R–

88 1U) (Extended Data Fig. 1).

89 Despite these dramatic differences in reproduction traits, phenotypic and genotypic

90 data revealed oviparous–viviparous hybrids. We found that 14.0% of adults inherited at least

91 10% of their genome from the alternative parity mode and that 6.1% of adults were first-

92 generation (F1) hybrids (Fig. 1V). F1 hybrid females (45–55% genomic admixture) were

93 intermediate between viviparous and oviparous characteristics with respect to eggshell

94 thickness (mean: 26.7 ± 2.3 μm; 13.0 ± 2.9% Ca), gestation time (mean: 25.8 ± 1.4 days) and

95 developmental stage at oviposition (mean: stage 33.9 ± 0.4) (Figs. 1J–1M and 1V). To the

96 best of our knowledge15,17, this is the first definitive evidence of contemporary natural

97 hybridisation between oviparous and viviparous lizards.

98

99 The genetic bases of the parity modes

100 This striking hybridisation between parity modes presents a natural genetic crossing

101 experiment for determining the genetic architectures of oviparity and viviparity. Using

102 genotypic and phenotypic data from females (N = 458; 80,696 single nucleotide

103 polymorphisms (SNPs)), we admixture-mapped two essential reproductive traits, i) the

104 gestation time (a score combining the number of external incubation days and the embryonic

105 stage at oviposition/parturition per clutch) and ii) the eggshell traits (a score calculated from

106 the eggshell/membrane thickness and calcium content), using linear mixed models (Extended

107 Data Figs. 2, 3). To identify relevant genes and biological processes, we estimated the

108 chromosome-wide linkage disequilibrium (LD) decay from a whole genome resequencing

109 dataset (N = 65 admixed females; mean genome coverage 4.1× each) (Supplementary Table

5 110 1). Genes within the same chromosome-specific LD-window as the SNPs associated with

111 gestation time and/or eggshell traits (Extended Data Fig. 4) were considered candidate genes.

112 We found that eggshell traits and gestation time were both highly genetically

113 determined and that our experiment had the ability to resolve these traits with great fidelity,

114 even in this complex natural population. The phenotypic variance explained by the genotype

115 data was very high: gestation time = 0.97 (95% CI = 0.96–0.98) and eggshell traits = 0.98

116 (95% CI = 0.96–0.98) (Supplementary Table 2). Genome-wide, 221 genetic variants (488

117 genes) were significantly associated with reproductive traits (adjusted P < 0.01). More

118 genetic variants were associated with the gestation time (210 SNPs, 439 candidate genes)

119 than with the eggshell traits (17 SNPs, 38 genes), indicating that the genetic basis of embryo

120 retention is more complex than that of the eggshell traits (Supplementary Table 3). From the

121 17 SNPs associated with eggshell traits, an excess was shared with gestation time (6 when the

122 expected shared SNPs by chance is 0.05; P < 0.0001; 11 genes). These SNPs were located on

123 a locus on chromosome 7 (two SNPs within 100 bp) and on a locus on chromosome 3 (two

124 SNPs within 100 bp), and two SNPs were located on unplaced scaffolds. The candidate genes

125 were significantly enriched for eight pathways, including the immune system response (Fas

126 signalling and T-cell activation) and tissue remodelling (the cadherin signalling pathway)

127 (Supplementary Table 4).

128 For gestation time, significant associations were found on most chromosomes (total

129 accumulated span of 41.2 Mb; Supplementary Table 3; Fig. 2a; Extended Data Fig. 5), with

130 an excess on chromosome 8 (64 significant SNPs; total span of 19.4 Mb) (Fig. 2a). The

131 candidate genes were significantly enriched (P < 0.01) for processes associated with cell

132 growth, proliferation and death (Supplementary Table 5), indicative of tissue remodelling.

133 The three SNPs most highly associated with gestation time were found close to the LYPLA1

134 (chr. 7), PGRMC1 (chr. 8) and SOCS2 (chr. 14) genes, all of which have reproductive

6 135 relevance. LYPLA1 has been previously associated with pregnancy in mammals18. PGRMC1

136 is a progesterone-binding membrane receptor protein highly expressed in mammalian

137 placentae19. Progesterone levels are essential for embryonic implantation in the uterus and

138 control development and ultimately parturition of the fetus20,21, and the introgression of

139 Neanderthal variants into modern humans is associated with higher fertility22. SOCS proteins

140 are negative regulators of pro-inflammatory cytokines and therefore modulate the maternal

141 immune response during pregnancy23.

142 For eggshell traits, significant associations were found on chromosomes 1, 2, 3, 7, 10,

143 11 and 14 (total span of 3.3 Mb; Supplementary Table 3; Fig. 2b; Extended Data Fig. 5).

144 Genes were significantly enriched (P < 0.01) for processes related to cell communication and

145 the immune system (Supplementary Table 6). The three loci that showed the strongest

146 associations with eggshell traits mapped closely to the LGMN (chr. 3), LYPLA1 (chr. 7) and

147 CRTC1 (chr. 2) genes (Fig. 2). These genes have clear functional relevance for amniote

148 reproduction. LGMN is upregulated in placenta and uterine tissues5,24 and is associated with

149 the cadherin pathway, which establishes the interconnectivity between the maternal–fetal

150 membranes4, and LYPLA1 plays a role in mammalian pregnancy18 and was highly associated

151 with gestation traits in our study. CRTC1 is a transcription coactivator involved in calcium

152 augmentation25 and mice fertility26 and has been correlated with egg productivity in birds27.

153

154 Developmental pathways regulating the parity modes

155 We compared the gene expression between functional reproductive tissues (oviduct) from

156 female oviparous and viviparous common lizards during reproductive (early pregnancy and

157 mid-pregnancy) and post-reproductive (after oviposition/parturition) time periods using

158 RNAseq (Supplementary Table 7) (N = 17). Early pregnancy represents the period when

7 159 oviparous and viviparous females have completed vitellogenesis and started ovulation.

160 Meanwhile, at mid-pregnancy, ovulation is completed and, in oviparous females, the eggshell

161 is formed28. At reproductive stage, we found 2610 genes that were significantly differentially

162 expressed between the parity modes (Extended Data Fig. 6; Fig. 3a). Differentially expressed

163 genes were functionally involved in 10 enriched biological pathways, including significant

164 enrichment (P < 0.05) for apoptosis signalling and the Parkinson disease pathway

165 (Supplementary Table 8). We speculate that the former may regulate the tissue remodelling

166 occurring at the interphase of the embryonic membranes and uterine tissue and that the latter

167 includes genes involved in vesicular transport, a function that is particularly important during

168 mid-term pregnancy in mammalian placentae29.

169 We found a significant relationship between gene expression in reproductive tissue

170 and the genes inferred from mapping the parity mode traits (more overlap than expected by

171 chance; 98 out of 488 candidate genes were also differentially expressed; P < 0.0001) (Fig.

172 3b). This included LYPLA1, a top candidate from genetic mapping that was downregulated

173 in the viviparous oviduct. Further, genome-wide p-values for differential expression were

174 correlated with genome-wide differentiation (FST) (estimate = −0.034; P = 0.017), indicating

175 that differentially expressed genes were more likely to be located in genomic regions with

176 higher genetic differentiation between the parity modes.

177 Three gene co-expression modules were associated with parity mode (FDR < 0.05).

178 Significantly enriched pathways associated with the two modules overexpressed in the

179 viviparous oviduct (total genes = 1245) included angiogenesis, the vascular endothelial

180 growth factor signalling pathway and the Beta 1 and 2 adrenergic receptor signalling

181 pathways (Supplementary Table 9). The module overexpressed in the oviparous oviduct

182 (total genes = 203) was significantly enriched for the transforming growth factor beta

183 signalling pathway (Supplementary Table 9), which regulates growth and cell proliferation30.

8 184 Therefore, both viviparous and oviparous oviduct tissues experience significant cell structure

185 changes during reproductive stages and these changes involve more genes and pathways in

186 viviparous tissue than in oviparous tissue.

187 To pinpoint key regulators, we conducted a hub gene search based on the three co-

188 expression modules associated with parity mode. We identified a total of 64 (51 annotated)

189 hub genes (Supplementary Table 10), which were significantly enriched for biological

190 processes associated with cellular structure and extracellular communication, such as the

191 establishment of cell polarity, epithelium development and biological adhesion

192 (Supplementary Table 11). Four hub genes overlapped with our candidate genes identified

193 from the genetic mapping, which is more than expected by chance (3.2× fold enrichment; P =

194 0.036), two of which (RAPGEF2 and RHOG) were located on chromosome 8. RAPGEF

195 genes are key regulators of cell adhesion, secretion, proliferation, differentiation31,32 and

196 blood formation in extraembryonic membranes33. RHOG is involved in cell migration34. The

197 other two genes were MAP1A (chr. 11), a protein involved in microtubule formation35

198 implicating a potential role in vesicular transport, and KANK3 (chr. 2). KANK genes are co-

199 opted for vertebrate vascular development36, which might be related to the vascularization of

200 uterine membranes required for viviparity. Therefore, the functional genomics of parity mode

201 that we identified have confirmed roles in vertebrate reproduction and are underpinned by the

202 genetic bases that we inferred.

203

204 Selection on parity mode

205 Having identified relevant heritable genetic variations, we applied a principal component

206 analysis-based evaluation to directly infer the loci linked to the alternative parity modes (N =

207 717 adults from the sample locality, ranging from pure oviparous to pure viviparous,

9 208 including hybrids, for 83,696 SNPs). This made it possible to extract the relationship between

209 the functional genes of a parity mode and the genome-wide response to selection while

210 holding the environment constant. In total, 1050 SNPs showed significant selection signals (q

211 < 0.01) and these SNPs were distributed across the genome (Extended Data Fig. 7). Using

212 our LD-decay approach (Extended Data Fig. 4), we identified 1621 candidate genes. Highly

213 enriched pathways for these genes included immune system response genes (Fas signalling; P

214 = 0.05), blood formation and vascularisation (angiogenesis), and tissue remodelling (the

215 cadherin signalling pathway and epidural growth factor receptor signalling pathway)

216 (Supplementary Table 12). Five of the top 10 most enriched pathways that showed genes

217 with a response to selection were also enriched for genes associated with parity mode (Tables

218 S5 and S14). We found a significant overlap of SNPs under selection and the genetically

219 controlling parity mode (N = 67, 30.3% SNPs shared), and a functional link was apparent

220 from the significant overlap (N = 312) between the genes differentially expressed in the

221 oviduct and the genes under selection (7.8% genes shared; P < 0.0001). This indicates that a

222 large fraction of the genes under selection are functionally relevant for the alternative parity

223 modes.

224 Genomic regions showing a response to selection also had high levels of

225 differentiation (FST) between parity modes, while nucleotide diversity within parity modes

226 was low in these regions (Extended Data Fig. 8). Significant correlation of the selection

227 scores with the divergence between parity modes (Extended Data Fig. 9a), the high overall

228 diversity (Extended Data Fig. 9b), and the low nucleotide diversity within the parity modes

229 (Extended Data Figs. 9c, d) suggests that these regions are not only under divergent selection

230 between parity modes but also under directional selection within parity modes, potentially

231 because they contain crucial genes controlling reproductive traits. The majority of SNPs

232 under selection and the genetically controlling parity mode (N = 67) had high FST and were

10 233 fixed, or nearly fixed, between parity modes, while another set of SNPs had low FST (below

234 0.5; Fig. 3A). While dominance effects may explain this, all except one of these SNPs (total

235 N = 23) were located on the sex chromosome 8. Because females are heterogametic and

236 therefore only carry a single copy of an allele on the sex chromosome, these FST differences

237 could be epistatic effects37. In particular, several SNPs associated with gestation time had FST

238 values near 0.25 and, in most cases (17 out of 23), the viviparous mode exhibited the derived

239 allele with lower frequency. No such SNPs were found for the eggshell traits (Fig. 3B),

240 indicating that this trait is under a simpler genetic control and that selective constraints affect

241 the parity modes differently. In summary, we found a large proportion of genes showing

242 selection signals between the two parity modes, of which many were associated with

243 pathways in vertebrate reproduction, as well as other potential adaptive responses.

244

245 Shared genetic and developmental programs of viviparity across vertebrates

246 Having shown the functional genomic mechanisms of ancestral oviparous and derived

247 viviparous parity modes in common lizards, we aimed to determine the extent that these

248 molecular pathways are shared more broadly. We compiled two databases: i) genes

249 differentially expressed between squamate oviparous–viviparous sister lineages that diverged

250 <30 Mya14,38 (N = 3 squamate genera) and ii) genes differentially expressed in the

251 reproductive organs of viviparous amniotes during pregnancy compared to during non-

252 pregnancy stages (N = 11, spanning five squamate families/subfamilies, five orders of

253 mammals (even-toed and odd-toed ungulates, carnivores, marsupials, and primates) and

254 seahorses).

255 We found that the genes differentially expressed across three evolutionarily

256 independent transitions from oviparity to viviparity in squamates overlapped significantly. A

11 257 total of 166 (out of 3039) genes were shared across two transitions; the overlap between

258 common lizards and agamid lizards was highly significant (N = 99 genes; exact t-test: P <

259 0.001), while the other two comparisons were not (Supplementary Table 13) (Fig. 5a). Even

260 though these are deeply divergent squamate lineages (with shared origins ~180 Mya), a

261 significant excess of genes (eight) were shared across all three oviparous–viviparous

262 comparisons (exact t-test: P < 0.001; Supplementary Table 13; Fig. 5a).

263 Comparing the pregnant and non-pregnant states for viviparous squamates, the

264 differentially expressed (DE) gene sets overlapped across most groups (22 out of 26 species

265 comparisons had significantly overlapping DE genes; Supplementary Table 14). Across all

266 squamates and the 9057 genes involved, 1 gene (CDH5) was shared between all five groups

267 and another 31 genes were shared across four groups (Supplementary Table 15). Sharing

268 across viviparous mammals was higher (all species comparisons were significant; Extended

269 Data Fig. 10; Supplementary Table 16) (Fig. 5b). Out of 8509 differentially expressed genes,

270 5 genes were shared across all five mammalian orders and 41 genes were shared by four

271 orders (Supplementary Table 17). These genes could be considered a core developmental

272 gene set for regulating reproductive tissue functionality and pregnancy in mammals because

273 they are enriched for the biological processes of the morphogenesis of a branching structure,

274 regulation of vascular development, and urogenital system development (Supplementary

275 Table 18). The high degree of sharing across viviparous mammals may be because all share a

276 single common ancestor (viviparity arose once in therian mammals, ~175 Mya39).

277 Conversely, the viviparous squamates included here represent five independent transitions to

278 viviparity between 4 Mya and 67 Mya38. As a consequence, the overlap we identified reveals

279 marked convergence in the developmental genes recruited for the evolution of viviparity in

280 squamates (Supplementary Table 14; Fig. 5b).

12 281 We found substantial sharing of differentially expressed gene sets across viviparous

282 vertebrates: mammals, squamates and seahorses (Fig. 5c). For example, out of 132

283 comparisons with at least three viviparous species sharing significantly overlapping DE gene

284 sets, 85 consisted of at least one squamate and one mammal, revealing considerable sharing

285 across divergent amniote groups (Supplementary Table 19). There was less overlap with the

286 seahorse, which is an anamniote (shared genes across groups: mammals: 42.3%, squamates:

287 40.0%, seahorse: 15.2%; Fig. 5c). Nonetheless, a significant number of genes is also shared

288 between seahorses and amniotes (i.e. 227 out of the 311 genes shared with at least one other

289 group; Supplementary Table 19). Overall, we find a strong convergence in pregnancy genes

290 across amniotes with less, but still significant, overlap between amniotes and anamniotes.

291

292 Discussion

293 While viviparity has evolved from oviparity repeatedly in vertebrates1, this is the first

294 experimental evidence, to the best of our knowledge, for the functional genetic architectures

295 of parity modes. Several lines of evidence suggest that eggshell characteristics are under

296 much simpler genetic control than the gestation time. Because different reproductive traits

297 have different genetic architectures, we suggest that this may directly impact the likelihood

298 and mechanism of transitions from oviparity to viviparity. Future work is required to identify

299 the minimal genetic differences determining the parity mode and to recapitulate its

300 evolutionary steps.

301 Our meta-analysis of vertebrate reproduction genes demonstrates that the functional

302 genetic architectures inferred from this common lizard natural model are broadly relevant.

303 First, there was significant overlap between the genes that were consistently differentially

304 expressed in reproductive tissues across divergent viviparous vertebrates (≥2 species) and the

305 genes identified in our common lizard genetic mapping experiment (208 out of 488 candidate

13 306 genes from genetic mapping, P < 0.001). Of the 38 candidate genes that also showed

307 overlapping differential expression across at least four viviparous vertebrates, the most

308 commonly shared genes were ASAH1, PLP1, SLC22A23 and EPAS1 (Supplementary Table

309 20). These genes act in transmembrane transport (PLP1 and SLC22A23), cell differentiation

310 (ASAH1) and vascularisation (EPAS1) and are involved in the establishment of pregnancy,

311 immune response and preeclampsia4,40,41. CDH5 was the only gene differentially expressed in

312 all pregnant squamates; cadherins are calcium-dependent cell adhesion proteins known to be

313 key regulators of reproductive tissues42, which we found to be involved in the genetic basis of

314 the eggshell traits and responding to selection. Other strongly implicated candidate genes

315 extensively shared across viviparous vertebrates included LYN, LYPLA1, LGMN, and

316 KANK3 (Supplementary Table 20). Second, of the 51 annotated hub genes we found

317 between oviparous and viviparous common lizards, 32 were differentially expressed in at

318 least two other viviparous vertebrates (1.95× enrichment, P < 0.001). Three of these genes,

319 RAPGEF2, RHOG, and KANK3, were also functional candidates that we inferred from

320 genetic mapping. RAPGEF genes are relevant for blood formation in extraembryonic

321 membranes33,43, and each of the seven genes in the family (RAPGEF1-6, RAPGEFL1) was

322 differentially expressed during pregnancy in at least two viviparous species in our meta-

323 analysis, indicating that this gene family is crucial for live-bearing reproduction. RHOG is a

324 gene involved in cell migration34 that we found differentially expressed in four viviparous

325 squamates and mammals. KANK genes are key in vertebrate vascular development36, and we

326 speculate that they may play a role in the well-vascularized uterine membranes required for

327 viviparity in squamates and mammals. Altogether, our results quantitatively show that similar

328 developmental pathways controlling viviparous reproduction have evolved repeatedly across

329 vertebrates. The high level of convergence suggests that pre-established regulatory networks

330 are used 3 and that these networks are often related to immunity, tissue remodelling and blood

14 331 vessel generation. Given that fish, mammals and squamates have independently evolved

332 viviparity over the past ~450 million years39, this implies that the functional genes controlling

333 parity mode tend to evolve repeatedly.

334 The evolution of key innovations, such as live-bearing reproduction, eyes, scales, and

335 feathers, offer unprecedented possibilities to exploit new ecological niches and are associated

336 with exceptional diversification44. Viviparity is associated with increased speciation rates,

337 more complex parental behaviour, and ecological niche expansion1,2,45. Our study shows how

338 this ecological and evolutionary innovation is underpinned by a trait-specific genomic

339 architecture, involving particular and often deeply shared genes and pathways. We speculate

340 that other origins of viviparity and differences from oviparity will involve similar key

341 pathways, controlled by some common functional genes, coordinated in a modular, trait-

342 specific fashion.

343

344 Online content

345 Full methods are provided in the supplementary material including Tables S1-S21 and

346 supplemental references.

347

348 Methods

349 Biological samples: Adult common lizards were sampled April-August 2014 – 2017 in

350 Carinthia, Austria15,12 (for detailed methods, see Supplementary). Pregnant females were

351 housed individually in terraria (following46) and phenotyped (N = 480) for reproductive

352 mode: i) number of external incubation days after parition, ii) embryonic stage at parition,

353 and iii) eggshell thickness. A small subset of females were sampled for oviducts (Table S8).

354 Clutches were weighed, staged, and measured for hatching time and success.

15 355 Eggshell/membrane thickness was measured by scanning electron microscopy (SEM).

356 Calcium composition of eggshell was measured by energy-dispersive X-ray spectroscopy

357 (EDX). Combining these, an ‘eggshell’ score was calculated for each female. We calculated a

358 gestation time score for each female from the embryonic stage at parition47 and the number of

359 external incubation days.

360 Genomics: Double-digest RAD Sequencing (ddRADSeq) libraries were prepared with

361 enzymes PstI and MspI following12. Genome-referenced16 genotypes were inferred in

362 STACKS version 1.4448. Individual genomic ancestry was inferred by ADMIXTURE

363 vers.1.349 with two genetic clusters. For each phenotyped female, the correlation coefficient

364 with the genome-wide degree of admixture (Q-value) was estimated. A subset of hybrid,

365 oviparous, and viviparous females were additionally selected for genotyping by whole

366 genome re-sequencing (Table S1).

367 Females with reproductive trait data and ddRADSeq genotypes were admixture

368 mapped using GEMMA vers. 0.9850. First, a Bayesian sparse linear mixed model (BSLMM)

369 was used to infer associations between genotypes and two phenotypic scores: gestation time

370 and eggshell characteristics. Second, a linear mixed model (LMM) was performed on all four

371 reproductive phenotypes (external incubation days, embryonic stage at parition, eggshell

372 calcium, eggshell thickness), and the two combined phenotype scores for gestation time and

373 eggshell characteristics.

374 The whole-genome dataset was used to quantify regional and genome-wide linkage

375 disequilibrium and its LD decay. We used the chromosome-specific half-life as linkage

376 boundary for each candidate SNP from admixture mapping to empirically determine the

377 regional candidate genes. We performed pathway enrichment analyses using the PANTHER

378 option in WebGestalt51 on this set of genes, using the chicken genome RefSeq protein dataset

379 (GCA_000002315.5) as a reference.

16 380 Analyses of genome-wide divergence were based on the ddRADseq genotype matrix

381 between purely (Q>99%) oviparous and viviparous individuals. Nucleotide diversity was

382 calculated in sliding windows of 50,000 sites52. Haplotype-based Fst values were extracted

383 from STACKS. Outliers in nucleotide diversity were identified by estimating the top 5% and

384 lowest 5% quantiles across the genome of each reproductive mode. Fst outliers were

385 identified as the top 5% quantiles. PCAdapt53 was used to identify candidate genomic loci

386 under selection between parity modes, with a threshold of q = 0.01. We identified the genes

387 in linkage with outlier loci using the LD block inference method from admixture mapping.

388 We tested for pathway enrichment of candidate genes and candidate SNPs (inferred by

389 association and selection) using PANTHER.

390 Gene expression: RNAseq data from oviduct tissue were aligned to the reference genome16

391 using STAR vers. 2.5.2b54 and normalised55. Count data were log2 scaled using the rlog

392 function in DESeq2. Then a principal component analysis was conducted using the svd

393 approach in the R package pcaMethods and a redundancy analysis (RDA) generated using the

394 R package vegan. Reproductive stage was specified as a ‘condition’.

395 To identify genes associated with parity mode, we performed separate differential

396 expression analyses with DESeq2 to identify sets of differentially expressed genes (DEGs)

397 between parity modes within and across stages, and only considered genes that were

398 significantly differentially expressed (adjusted p-value: 0.01) during a reproductive stage.

399 Second, we used a Weighted Gene Co-Expression Network Analysis (WGCNA) to identify

400 modules of co-expressed genes associated with parity mode56. Pearson’s correlations were

401 calculated between module eigengenes (the first principal component of the module’s

402 expression profile) and trait measurements (parity mode and reproductive stage). Positive

403 correlations represent up-regulation in viviparous (vs. oviparous), and negative up-regulation

404 in oviparous (vs. viviparous). To identify key regulator genes, we identified a set of hub

17 405 genes for all modules significantly associated with parity mode. Hub genes were selected

406 based on being within the top 10% quantile of the module membership (MM) scores and

407 gene significance (GS) scores.

408 We performed separate functional enrichment analyses on the parity-associated genes

409 sets identified using differential expression and WGCNA analyses, using the PANTHER

410 classification57. Gene Set Enrichment Analyses (GSEAs)51 were used to identify significantly

411 enriched pathways for DEG gene sets using ranked expression scores. To identify pathways

412 that were enriched within parity-associated co-expression modules, we performed individual

413 Over-Representation Analyses (ORAs) for each module. The background gene set for all

414 GSEA and ORA analyses was specified as the full set of 21,187 genes in the genome16.

415 Developmental pathways meta-analysis: Using gene symbols from previous studies, we

416 assessed the overlap between differentially expressed genes between oviparous and

417 viviparous squamate reproductive tissue from three lizard systems (Saiphos equalis7, Zootoca

418 vivipara and sister species in genus Phrynocepahlus6) (Supplementary Table 21). We

419 assessed the overlap of the three gene symbol lists and if intersections exceeded that expected

420 by chance (based on a total gene set of 20,000 genes typical of vertebrates58) using the R

421 package ‘SuperExactTest’59.

422 To assess among a breadth of vertebrates, we compared differentially expressed genes

423 in reproductive tissues of pregnant viviparous species relative to their non-pregnant states.

424 This included: mammals Canis lupus (wolf), Equus caballus (horse), Homo sapiens (human),

425 Monodelphis domestica (opossum), and three closely related even-toed ungulates (Bos

426 taurus, Capra aegagrus, and Sus scrofa) combined into a single gene set; squamate bimodal

427 Saiphos equalis and Zootoca vivipara, Phrynocepahlus vlangalii, and two independently

428 viviparous skinks Chalcides ocellatus and Pseudemoia entrecasteauxii; and an anamniote

429 outgroup, the seahorse Hippocampus abdominalis. The final data set consisted of 11 gene

18 430 sets (five mammalian, five squamate, one fish) composed of 13 species (Supplementary

431 Table 21), and representing seven independent origins of viviparity across vertebrates1.

432 Intersections between gene sets were again assessed using ‘SuperExactTest’59 for: i) overlap

433 of genes across mammalian gene sets, ii) overlap of genes across viviparous squamate gene

434 sets, and iii) overlap of genes across all vertebrate viviparous gene sets. Biological pathway

435 enrichment analyses were performed in WebGestalt51 for the genes shared by more than four

436 groups within the mammals and squamates.

437 Data availability: The raw sequence data presented in this paper can be found in NCBI

438 (accession number with acceptance), and the phenotypic, genotypic, differential expression

439 data, vertebrate gene lists, and any required code can be found on University of Glasgow

440 Enlighten (doi with acceptance).

441

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22 589 Acknowledgments: We thank the late W. Mayer for his support and guidance in developing

590 the project. For technical assistance, we are grateful to A. Adams, M. Capstick, M. Mullin,

591 and J. Galbraith. We thank K. Schneider for assistance with whole-genome re-sequencing

592 libraries. We thank H. Leitao, T. Caribe da Rocha, M. Mullin, and J. Gallagher for help with

593 eggshell sample preparation and calcium content measurements. We thank R. Page for

594 support in project development, A. Jacobs for discussions and comments on data analysis,

595 and T. Stevenson for comments on a draft. We thank G. Migiani for creating illustrations.

596 Finally, many thanks are due to the field assistants M. Andrews, M. Capstick, R. Carey, K.

597 Gallagher-Mackay, M. Lamorgese, N. Lawrie, M. Layton, H. Leitão, J. McClelland, G.

598 Migiani, M. Raske, J. Smout, and M. Sutherland who helped with sampling and husbandry.

599 Research was funded by a Genetics Society Heredity Fieldwork grant to H.R.; a University of

600 Glasgow Lord Kelvin/Adam Smith PhD Studentship to K.R.E. and N.K. for H.R.; NERC

601 grants NE/ N003942/1 to K.R.E., R. Page and M.M.B., NBAF964 to K.R.E., and NBAF1018

602 to K.R.E. and A.Y.

603

604 Author contributions: H.R., M.M.B. and K.R.E. designed and led the project. H.R. and

605 K.R.E carried out the fieldwork. H.R. conducted the phenotypic analyses, generated and

606 analysed the genomic data and genetic mapping, generated and interpreted the transcriptome

607 data and compiled and analysed the comparative analyses. M.N. staged the embryonic

608 development. M.C. conducted transcriptome bioinformatics. A.Y. assembled and annotated

609 the reference genome and conducted whole genome bioinformatics. H.R. and M.M.B.

610 conducted the eggshell microscopy. H.R. and M.C. produced the figures. H.R. and K.R.E.

611 wrote the manuscript with contributions from M.C. and A.Y. All authors contributed to

612 interpreting the results and revising the manuscript.

23 613

614 Competing interests: We declare no competing interests.

615

616 Correspondence and requests for materials should be addressed to K.R.E.

24 617

618

619 Fig. 1. Natural hybridisation and backcrossing between oviparous and viviparous

620 common lizards result in intermediate phenotypes and genotypes. a, b, c, d, In clutches

621 laid by oviparous females, (a) eggshells are more calcified and have longer external

622 incubation times (~35 days), (b) embryos are at an earlier developmental stage (stage ~31),

25 623 (c) eggshells have fewer calcium crystals (~25%) and (d) eggshells are thicker (~50 μm). r, s,

624 t, u, Offspring from viviparous females (r–s) emerge from thin membranes within hours to a

625 few days (~1.9 days) and are fully developed (stage 41). Membranes have (T) no calcium

626 crystals (~1.6%) and (U) are much thinner (~4 μm). e, f, g, h, Hybrid females that

627 backcrossed with oviparous lizards have generally thinner eggshells and embryos that are at a

628 later developmental stage compared to oviparous females. j, k, l, m, F1-hybrids are

629 intermediate between oviparous and viviparous phenotypes. n, o, p, q, Females backcrossed

630 with viviparous lizards have short incubation times and thinner eggshells. v, This is reflected

631 by the genotypes of common lizards in the examined contact zone shown in panel. Genome-

632 wide ancestries differ considerably and show varying proportions of ‘oviparous’ and

633 ‘viviparous’ ancestral genomes in admixed individuals.

26 634

635 Fig. 2. Genetic architecture of parity mode. a, b, Admixture mapping reveals genetic

636 variants associated with (a) the gestation time and (b) the eggshell traits. The genome-wide

637 significance is indicated by the horizontal red dotted line, while the blue line indicates a p-

638 value threshold of <0.01 using the Benjamini–Hochberg correction.

27 639 640

641 Fig. 3. Differential expression analyses between oviparous and viviparous oviduct tissue

642 during pregnancy. a, Differentially expressed genes during the reproductive stages

643 (pregnancy). Genes that show significant differential expression (adjusted p-value < 0.05)

644 and a strong difference in expression (Log2-fold change threshold > 1×) between the two

645 parity modes are shown in red. Genes showing relatively higher expressions in oviparous

646 oviducts have more negative Log2-fold changes, while those overexpressed in viviparous

647 oviducts have more positive Log2-fold changes. Blue-coloured genes show significant p-

648 values but relatively low differential expression (<1× Log2-fold change), while beige-

28 649 coloured genes show higher Log2-fold changes (>1×) but low p-values (>0.05). Grey-

650 coloured genes show low differential expression (Log2-fold change <1×; p-value > 0.05). b,

651 Differentially expressed genes during reproductive stages across the genome. Candidate

652 regions identified from admixture mapping are illustrated in red, and differentially expressed

653 (adjusted p-value < 0.05) genes falling into these regions are also shown in red, with the gene

654 density shown on the top in grey.

29 655

656 Fig. 4. Genome-wide analysis of the selection score versus the genetic differentiation

657 (FST) between adult common lizards spanning oviparity to viviparity (64,846 loci). c, d,

658 Genetic variants associated with reproductive traits from genetic mapping of (c) the gestation

659 time and (d) the eggshell traits are highlighted in red.

30 660

661 Fig. 5. Overlap between differentially expressed genes in pregnant and non-pregnant

662 viviparous organisms. a, Overlap in therian mammals, all sharing a common viviparous

663 ancestor. All intersections are significant, meaning that all viviparous mammals share similar

664 genes for regulating pregnancy. b, Overlap across squamate reptiles. All five species have

665 different viviparous ancestors, i.e. viviparity independently arose in all five cases.

666 Intersections across all groups are significant. c, Overlap across amniotes and a seahorse

667 species. Only significant (P < 0.001) intersections with at least four species are shown.

31 668 Sharing was extensive between all amniotes but less extensive with the seahorse (H.

669 abdominalis).

32 670 671

672 Extended Data Fig. 1. Distribution of common lizards in Europe. a, The distribution of

673 oviparous (red) and viviparous (blue) common lizard lineages. b, The sampling area for this

674 study, a contact zone in Austria with overlapping oviparous and viviparous common lizards,

675 including hybrids (Q-value 0.1-0.9).

33 676

677

678 Extended Data Fig. 2. Histograms of all reproductive phenotypes describing parity

679 mode characteristics. a, The number of external incubation days was measured for each

680 clutch in the field, and b, one sample per clutch was taken to identify the embryonic stage at

681 oviposition/parturition. c, From these two phenotypes, a gestation time score was calculated,

682 where 0 is more viviparous and 1 is more oviparous. To describe eggshell characteristics, d,

683 calcium content and e, eggshell thickness were measured for one eggshell per clutch. f, From

684 these two phenotypes, an eggshell score was calculated for each individual, where 0 is more

685 viviparous and 1 is more oviparous.

34 686 687

688 Extended Data Fig. 3. Correlation between reproductive phenotypes and genome-wide

689 ancestry. Correlations between reproductive traits and summary scores for a, - c, gestation

690 time and d, - f, eggshell characteristics are shown plotted against genome-wide Q-value for

691 parity mode (0 = oviparous, 1 = viviparous) inferred from ADMIXTURE.

692

35 693 694

695 Extended Data Fig. 4. Decay of linkage disequilibrium (LD) in candidate regions for

696 chromosomes containing SNPs significantly associated with parity mode.

36 697 698

699 Extended Data Fig. 5. Genetic associations between reproductive phenotypes and 80,696

700 SNPs. a, b, c, d, Manhattan plots of admixture mapping on the four individually measured

701 reproductive traits. The genome-wide significance is indicated by the horizontal red dotted

702 line, while the blue line indicates a p-value threshold of <0.01 using the Benjamini–Hochberg

703 correction.

37 704 705

706 Extended Data Fig. 6. RNA expression across 14,102 genes for oviparous and viviparous

707 females at different reproductive stages in multi-dimensional space. a, shows a principal

708 component analysis (PCA), and b, a redundancy analysis (RDA).

38 709 710

711 Extended Data Fig. 7. Selection scan across the genome. Out of a total of 80,696 SNPs,

712 those highlighted in blue and red (N = 1051) showed significant signals of selection (BH

713 corrected p-value < 0.01). In addition, all SNPs in red (N = 128) fell within genomic regions

714 associated with reproductive mode phenotypes.

39 715

716 Extended Data Fig. 8. Genome-wide estimates of diversity and divergence. Nucleotide

717 diversity estimates within a, oviparous and b, viviparous common lizards. Smoothed means

718 are shown in red for oviparous and blue for viviparous. c, shows Fst across the genome.

719 Candidate regions are marked as red bars. Standard deviations of smoothed means are shown

720 in light grey.

40 721 722

723 Extended Data Fig. 9. Correlation between selection scores (shown as negative Log10 P)

724 and genetic diversity measures. SNP selection scores positively correlate with a, Fst and

725 with b, overall nucleotide diversity when all individuals are pooled. Within both c, oviparous

726 and d, viviparous parity modes, nucleotide diversity negatively correlates with selection

727 scores.

728

41 729

730 731

732 Extended Data Fig. 10. Overlap in differentially expressed genes between viviparous

733 mammals during pregnancy. Species comparisons in each histogram are shown in

734 turquoise circles. A phylogenetic tree of the lineages that evolved viviparity independently

735 show estimated divergence times. Note that all species diverged from a common egg-laying

736 ancestor more than 150 million years ago. ***P < 0.001.

737

42 1 2 3 Supplementary Materials for 4 5 The functional genetic architecture of egg-laying and live-bearing reproduction 6 7 8 9 H. Recknagel, M. Carruthers, A. Yurchenko, M. Nokhbatolfoghahai, N. A. Kamenos, M.M. 10 Bain, K. R. Elmer. 11 12 Correspondence to: [email protected] 13 14 15 This PDF file includes: 16 17 Detailed Materials and Methods 18 Supplementary Tables 1 to 21 19 Supplemental References 20

1

21 Materials and Methods 22 Sampling 23 Sampling was performed in a contact zone between oviparous and viviparous 24 common lizards in Carinthia, Austria1,2. Adult common lizards were caught in the years 2014 25 – 2017 between April and August. Males and females were distinguished by the presence of 26 bulge at the base of the tail in males. For each individual, non-lethal sampling by tail clip was 27 taken for later use in the genetic analyses. Individuals were then released at site of capture. 28 Female pregnancy was assessed by a presence of a bite mark on the female’s flank resulting 29 from mating. 30 Pregnant females were maintained in 20cmx35cmx15cm terraria and food was 31 provided ad libitum. For more detailed housing conditions see3. Females were checked for 32 the presence of a clutch on a daily basis and kept until parturition or oviposition [from here 33 on this time point is referred to as ‘parition’4], followed by their release at the point of 34 capture. All females (N = 480) that laid eggs or gave birth were phenotyped for reproductive 35 mode using three measures: i) number of external incubation days after parition, ii) 36 embryonic stage at parition, and iii) eggshell thickness. In addition, three females of each 37 reproductive mode were lethally sampled at three time points during pregnancy (early, mid, 38 and after gestation; total N = 18 females). From these, oviducts were extracted and preserved 39 in RNAlater (Supplementary Table 7). 40 Clutches were weighed using a smart weigh high precision scale (to the nearest 0.001 41 g), and one egg was removed from each clutch and fixed in formalin (24h in 10% buffered 42 formalin solution) and stored in 70% EtOH for later embryonic staging and eggshell analysis. 43 The remaining eggs were embedded in moist vermiculite before being incubated at 24ºC in 44 an ExoTerra reptile egg incubator. The number of external incubation days was recorded for 45 every hatchling or neonate of a clutch. The average across all offspring was then calculated 46 and used for genetic mapping analyses. All clutches were checked daily for appropriate 47 moisture, presence of infertile or dead embryos, or any hatching offspring. The number of 48 external incubation days per clutch was calculated as the average number of incubating days 49 for the clutch offspring that successfully hatched. Clutch survival was measured as the 50 proportion of successfully hatched individuals within a clutch. Offspring were released at the 51 mother’s point of capture. 52 53 Egg characteristics: 54 Thickness: To prepare and dehydrate eggshells for scanning electron microscopy 55 (SEM), half of each eggshell was removed and washed once in 90% EtOH, twice in 100% 56 EtOH, then twice in hexamethyldisilazane (HMDS) before being transferred to a desiccator 57 overnight. Under a light microscope, the dry eggshells and membranes were cut with a sharp 58 scalpel and mounted on aluminum mounts using double-sided sticky copper tape (AGG3397, 59 AGAR Scientific Ltd). Samples were stuck to the copper tape with the straight cut edges 60 facing upwards. The samples were then coated with gold-platinum for 250 sec using a 61 LEICA EM SCD005 machine to a thickness of about ~15nm. To ensure conductivity across 62 the sample, silver paint was carefully added to the base of each eggshell sample. Images were 63 taken of intact, straight edges of each sample at a magnification of 500x (for most oviparous 64 eggshells) or 1000x (for most viviparous membranes) on a Leica EM SCD005 scanning 65 electron microscope (SEM). Five measures were taken across each image using the linear 66 measurement tool and recorded. The average and standard deviation across the five 67 measurements were recorded for each sample. For a subset of samples (N = 42), a second 68 image from a different part of the eggshell was taken to assess the consistency across 69 different regions across the shell. These repeated measures showed that eggshell thickness

2

70 does vary across different regions of the shell, but is generally strongly correlated within a 71 sample (R2= 0.88, P < 0.0001). 72 Chemical composition (Ca content): Part of each fixed egg sample was removed and 73 mounted on an aluminum mount with an adhesive double-sided carbon coated disc (Agar 74 Scientific Ltd, UK) such that the outside of the eggshell/membrane was facing outwards. 75 Samples were then sputter-coated in vacuum with gold using a LEICA EM SCD005 for 76 160sec. Chemical composition of eggshells was assessed using energy-dispersive X-ray 77 spectroscopy (EDX). The relative contribution of carbon (C), oxygen (O), sodium (Na), 78 phosphorus (p), sulfur (S), calcium (Ca), magnesium (Mg) and potassium (K) were extracted. 79 Chemical composition of eggshells was measured on six different points of each sample’s 80 image and averaged. For subsequent admixture mapping analyses, the relative amount of Ca 81 only was extracted. For a set of samples (N=53), we extracted a second sample from the 82 same individual’s eggshell and repeated the whole process to estimate measurement error. 83 Overall, there was a strong correlation between the first and second Ca measurement (R2= 84 0.79, P < 0.0001). 85 An ‘eggshell’ score was calculated for each individual. Thickness and Ca traits were 86 first normalized by re-scaling values such that they varied between 0 (lowest viviparous 87 value) and 1 (highest oviparous value) 5. Because the two measures differed in consistency 88 and eggshell thickness proved to be more reliable both within samples (R2= 0.88 vs R2= 0.79) 89 and compared to the genomic background (R2= 0.86, vs R2= 0.56; Extended Data Fig. 3), we 90 weighted the two individual traits according to their Pearson correlation coefficient with 91 genomic background. For individuals that had only one of the two measurements, only that 92 single normalized score was retained. This resulted in a total of 434 egg clutches phenotyped 93 for eggshell characteristics. 94 95 Gestation time: Embryonic stage at parition and number of incubation days 96 Embryonic stage at parition was identified in the lab using a light microscope (Wild 97 M3Z dissecting microscope fitted with an eyepiece scale) and a staging table of common 98 lizards following Dufaure and Hubert (1961)6. Embryos were imaged with a Nikon D5100 99 DSLR camera with a Nikkor 40 mm lens camera at 6.3x to 40x magnification. 100 Similar to summarizing eggshell characteristics in a score, we calculated a gestation 101 time score by normalizing the embryonic stage at parition and the number of external 102 incubation days both to 1 and averaging across these two scores. Because the two phenotypes 103 were very similar in their correlation with genomic background (R2= 0.93 vs R2= 0.96, 104 Extended Data Fig. 3), these were not weighted. This resulted in a total of 403 individuals 105 phenotyped for gestation time. 106 107 Genotyping by ddRADseq 108 DNA was extracted from tail samples using the Macherey-Nagel NucleoSpin® Tissue 109 kit at a minimum of 20 ng/ul. Eight double-digest RAD Sequencing (ddRADSeq) libraries 110 with 105 individuals each (N = 798 [557 females and 241 males]) were then prepared with 111 restriction enzymes PstI and MspI following2. Each library was sequenced at Edinburgh 112 Genomics on an Illumina HiSeq 4000 at 2x150bp read length to ~5M reads per individual. 113 Technical replicates (N = 36) were included to calculate genotyping error rates. A total 114 number of 5.9 billion reads were obtained. 115 After sequencing, all reads were de-multiplexed with the barcode- and enzyme- 116 correction options in STACKS version 1.447. De-multiplexed reads were aligned to the Z. 117 vivipara reference genome8 using Burrows-Wheeler transform9 and SAMtools10 and sorted 118 into loci in Stacks allowing up to three mutations per locus and a minimum stack depth of 119 three reads.

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120 We removed multiple replicates of individuals sampled more than once across years 121 and retained the sample with the highest sequencing coverage. This was performed by 122 extracting genotypes from STACKS with a minimum coverage of 8x, presence in at least 123 50% of all individuals, and a minor allele frequency of 10%, and then running the software 124 KING vers. 2.1.511 using the --duplicate option. Out of the 798 individuals, 89 (11.1%) were 125 inferred as individuals that were sampled at least twice across years and excluded from all 126 following analyses. 127 Female (N = 495) and male (N = 222) genotypes (total N = 717) were extracted from 128 STACKS, with the same parameters as stated above. The genomic ancestry of each 129 individual was then inferred by a structure clustering method, ADMIXTURE vers.1.312 with 130 two genetic clusters (K = 2) and performing 10-fold cross-validation. The degree of 131 admixture was estimated from inferred membership values (Q). In cases where reproductive 132 data from females was present, the correlation between genotype and phenotype was 133 assessed. For each phenotype, the correlation coefficient with the genome-wide degree of 134 admixture (Q-value) was estimated. 135 136 Genotyping from whole genome sequencing 137 Fifty-nine females with hybrid genomic backgrounds, and three females with purely 138 oviparous and viviparous backgrounds, respectively, were chosen for low-coverage whole 139 genome re-sequencing (total N = 65; average of 4.1x coverage; Supplementary Table 1). 140 Genomic libraries were prepared using a modified protocol based on DNA tagmentation 141 using the Nextera DNA Flex Library Prep Kit and library amplification using the KAPA 142 Library Amplification Kit for Illumina13. In brief, high molecular weight DNA (> 25ng/ul) 143 was extracted using the Macherey-Nagel NucleoSpin® Tissue kit and then fragmented using 144 transposon cleavage, followed by tagging of the double-stranded DNA ends. Adapters and 145 sequencing primers were added to the tagged ends and amplified. This was followed by a 146 cleanup and size selection of DNA fragments ranging from 400-700 bp (average library size: 147 568 bp). Seven genomic libraries with a pool of 5 to 12 individuals at equimolar 148 concentrations were sequenced on a HiSeqX with 150 bp paired-end reads at BGI Tech 149 Solutions (Hong Kong). In total, ~4.74 billion reads were sequenced. 150 Individuals were de-multiplexed and aligned to a draft version of the Z. vivipara 151 reference genome8 using BWA-mem9 with the -M flag and resulting BAM files were sorted 152 with Samtools10. PCR duplicates were removed with GATK 414. To call genetic variants we 153 used the bcftools15 with multi-sample calling (-m) of all BAM files simultaneously for 154 improved identification of heterozygous variants in low-coverage data. Reads with a mapping 155 quality below 40 (phred-scaled) and nucleotides with quality scores lower than 25 were 156 excluded from variant calling (-q 40, -Q 25). The final VCF file was filtered using vcftools16 157 to remove variants with phred-scale quality less than 300 (--minQ 300) or with more than 45 158 missing genotypes or completely monomorphic. 159 160 Genetic mapping 161 All females (N = 458) with reproductive data and genotypes from ddRADSeq were 162 used for admixture mapping. Individuals were categorized as oviparous, admixed, or 163 viviparous by pre-assessed genomic background. Individuals with more than 90.0% 164 oviparous or viviparous genomes were assigned into those respective classes, whereas all 165 individuals in between those two classes were considered admixed. This was done to balance 166 the number of individuals with different genomic backgrounds irrespective of coverage 167 differences that can result from library preparation (e.g. slight differences in size selection) 168 and sequencing. Genotypes that were present in all three classes at a minimum of 60% per 169 class and a coverage of at least 8x were extracted for further analyses (a total of 80,696

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170 SNPs). The genotype matrix was phased and missing genotypes imputed using BEAGLE 171 vers. 06.201717. Phased genotypes were used as input for GEMMA vers. 0.9818. In GEMMA, 172 a relationship matrix between all individuals is first calculated to correct for population 173 stratification (in this case the two evolutionary lineages, oviparous and viviparous). First, a 174 Bayesian sparse linear mixed model (BSLMM) was used to infer associations between 175 genotypes and the two phenotypic scores: gestation time and eggshell characteristics. The 176 BSLMM was run 20 times, with 50 million iterations using a burn-in of 35 million. Runs 177 were visually inspected for convergence and the ten runs showing poorest mixing were 178 excluded19; the remaining ten runs were combined and the estimates averaged. From these 179 estimates heritability and the phenotypic variance explained by genotypic variance was 180 inferred. Second, for association mapping a linear mixed model (LMM) was performed on all 181 four reproductive phenotypes and the two combined phenotype scores for gestation time and 182 eggshell characteristics. The number of individuals included for each trait that was mapped 183 differed (N external incubation days = 390, N embryonic stage = 222, N eggshell calcium = 184 146, N eggshell thickness = 422, N gestation time score = 403, N eggshell traits score = 434). 185 Because not all traits were measured in each year and some incubating offspring failed to 186 hatch, the number of recorded traits per female differs. 187 The whole-genome dataset (N = 65) was used to assess regional and genome-wide 188 linkage disequilibrium. First, genotype likelihoods of filtered SNPs (min. depth = 90, max. 189 depth = 543, min. individuals = 49) were extracted for each chromosome. These were then 190 imported into ngsLD, and correlation coefficients were estimated for SNPs within a 191 maximum distance of 100kb. A random sample of 0.1% was exported from these analyses for 192 each chromosome. To assess linkage disequilibrium in candidate regions compared to 193 genome-wide background, candidate regions were derived using all SNPs significantly 194 associated (adjusted P value < 0.01) with gestation time or eggshell traits. We then extracted 195 R2 values of LD for each candidate region and compared it to the genomic background. 196 To assess which genes were associated with the SNPs identified in the mapping, we 197 first inferred average linkage block size for each chromosome. For each chromosome, we 198 estimated LD decay (which follows an exponential decay function) and extracted the half-life 199 for each chromosome’s LD curve. We used the chromosome-specific half-life as linkage 200 boundary for each SNP on its respective chromosome. Next, using these boundaries, we 201 extracted all genes lying within boundaries of all significantly associated SNPs. On this set of 202 genes we performed pathway enrichment analyses using the Protein Annotation THrough 203 Evolutionary Relationship (PANTHER) option in WebGestalt20. The RefSeq protein dataset 204 for the chicken genome (GCA_000002315.5) was used as a reference. 205 206 Genomic analyses of divergence, linkage and selection 207 A genotype matrix restricted to purely (>99% from the admixture analysis) oviparous 208 (N = 222) and viviparous (N = 238) individuals was extracted from STACKS using 209 genotypes present in at least 66% of individuals within both the oviparous and viviparous 210 lineage and a minimum allele frequency of 10%. Nucleotide diversity (pi) was calculated in 211 sliding windows of 50,000 sites using the ‘popgenWindows.py’ script21 available on GitHub. 212 Haplotyp-based Fst values were extracted from STACKS (Fst’ option). Outliers in nucleotide 213 diversity were identified by estimating the top 5% and lowest 5% quantiles across the 214 genome of each reproductive mode. Fst outliers were identified as the top 5% quantiles. 215 In addition, PCAdapt22 was run to identify genomic loci under selection between 216 oviparous and viviparous common lizards. In contrast to other methods such as scans of 217 selection using FST-based approaches that require a-priori definition of two groups for 218 comparison, this approach can handle substantially admixed individuals22 and was therefore 219 run on the full dataset of 717 individuals. We tested for up to K = 20, but the first principal

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220 component (PC) was the main predictor for divergence between the oviparous and viviparous 221 lineages and was therefore used for subsequent selection analysis. Genomic loci that were 222 significantly associated with PC1 were considered candidates under selection. We chose a 223 threshold of q = 0.01 for the determination of outlier loci for selection. Next we tested for 224 linkage of outlier loci with genes using the same LD block inference method as for admixture 225 mapping. We extracted all genes tested for enriched PANTHER pathways. In addition, we 226 extracted all SNPs (and the genes linked to those SNPs) that were both significantly 227 associated with the two mapped reproductive phenotypes and showed signals of selection and 228 performed pathway enrichment analyses on these. 229 230 Gene expression analyses 231 RNA was extracted from oviduct tissue of the 18 females during different 232 reproductive and developmental stages (Supplementary Table 7). Because tissues were stored 233 under suboptimal conditions in the field and RIN values after RNA extraction varied between 234 3-6, we used the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina® in 235 combination with the NEBNext® rRNA Depletion Kit to remove ribosomal RNA during 236 library preparation for RNA sequencing. Libraries were sequenced in three runs (run 1: N = 237 2; run 2: N = 7; run 3: N = 9) on an Illumina NextSeq 500 at Glasgow Polyomics using 238 paired-end sequencing at 150bp. 239 Prior to quality filtering, ribosomal RNA was removed from the sequenced RNA. 240 This was achieved by first constructing a reference database of Z. vivipara ribosomal RNA 241 by screening the reference genome8 for rRNA like sequences using barrnap vers. 0.623. All 242 rRNA sequences were then removed from the sequenced RNA using tagdust vers. 2.3324. The 243 rRNA cleaned reads were then processed with Trimmomatic vers. 0.3625 to remove any low 244 quality sequences prior to alignment. Leading and trailing bases with Phred quality score 245 below 20 were removed and a sliding window approach (4 bp window size) was used to trim 246 reads at positions with Phred scores below 20, allowing for a minimum read length of 50 bp 247 after trimming. Fastqc vers. 0.11.826 was used to assess read quality before and after 248 processing. Processing removed 40% of all reads, resulting in a dataset of 494 million 249 cleaned reads (range: 6.06M - 48.55M; Supplementary Table 7). Cleaned reads from each 250 library were aligned against the reference genome8 using STAR vers. 2.5.2b27, with default 251 parameters, and gene expression was quantified with HTSeq vers. 0.11.228 using the 252 parameters: --stranded = no, --order = pos, --type = CDS and idattr = Parent. 253 Given the varying degree of RNA degradation among our samples (indicated by RIN 254 values between 3-6) and the expected heterogenous pattern of degradation among transcripts 255 within samples, we quantified degradation across all transcripts and all samples using the 256 degradation normalisation pipeline DegNorm29. DegNorm normalisation is based on a non- 257 negative matrix factorization over-approximation algorithm that corrects for gene-by-gene 258 biases in degradation while simultaneously controlling for sequencing depth29. Briefly, the 259 algorithm works in two main steps; 1) it utilises the information from the alignment files for 260 each sample to generate coverage curves for expected and observed amounts of degradation 261 for each gene individually. This is then used to estimate a degradation index (DI) score for 262 each sample. 2) The generated DI scores are used to adjust the raw read counts for all genes 263 across all samples, while simultaneously normalising for sequencing depth. Both steps are 264 repeated until the algorithm converges. 265 In the current dataset, DegNorm highlighted one (out of 18) samples as having major 266 expression bias due to degradation. This sample (ELT08545, Supplementary Table 7) was 267 excluded from all further analyses. The degradation adjusted read counts for the remaining 17 268 samples were then filtered to remove genes with less than 10 read counts across 90% of 269 samples in the R package DESeq2 vers. 3.530.

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270 To identify the major axes of expression variation between samples from different 271 parity modes and reproductive stages, we performed a single principal component analysis 272 (PCA) on the full dataset (N = 17). The PCA was performed using the svd approach in the R 273 package pcaMethods. Expression patterns were assessed further by applying a single 274 conditioned redundancy analysis (RDA) on all individuals, using the R package vegan. 275 Reproductive stage was specified as a ‘condition’ within the model to control for expression 276 variation associated with differences between reproductive stages. All count data were log2 277 scaled using the rlog function in DESeq2 prior to conducting the PCA and RDA analyses. 278 To identify genes associated with parity mode, we applied two robust approaches. 279 First, we performed separate differential expression analyses with DESeq2, on the 280 degradation adjusted read counts, to identify sets of differentially expressed genes (DEGs) 281 between parity modes, both within and across stages. Finally, we only considered genes that 282 were significantly differentially expressed (adjusted p-value: 0.01) during a reproductive 283 stage (‘early and/or ‘mid’, but not ‘after’ gestation) as candidates of functional relevance. 284 Second, we used a Weighted Gene Co-Expression Network Analysis (WGCNA) to identify 285 modules of co-expressed genes associated with parity mode31. The R package WGCNA was 286 used to construct a single network for all 17 individuals, based on the log2 scaled count data. 287 Network modules were defined using the dynamic treecut algorithm, with a minimum 288 module size of 30 genes and a cut height of 0.981. The module eigengene distance threshold 289 was set to 0.25 to merge highly similar modules. Pearson’s correlations were calculated 290 between module eigengenes (the first principal component of the expression profile for a 291 given module) and trait measurements (parity mode and reproductive stage) to identify 292 modules that were significantly associated with parity mode. All P-values were Benjamini- 293 Hochberg corrected (FDR < 0.05). The direction of correlation (i.e. positive or negative) 294 determined whether modules were associated with expression in oviparous or viviparous 295 individuals. Trait values for parity mode were specified in binary format (oviparous = 0 and 296 viviparous = 1), therefore positive correlations represent up-regulation in the viviparous 297 individuals (vs. oviparous), and negative correlations represent up-regulation in oviparous 298 individuals (vs. viviparous). 299 To further identify genes which may act as key regulators of parity mode evolution, 300 we identified a set of hub genes (i.e., the most highly connected genes) for all modules 301 significantly associated with parity mode. Hub genes were selected based on two criteria. 1) 302 Module membership (MM) scores, which represents the correlation between the expression 303 levels of a gene and the module eigengene value. 2. Gene significance (GS) scores, which 304 represents the correlation between the expression levels of a gene and the biological trait of 305 interest. Genes within the top 10% quantile of both MM and GS scores were considered hub 306 genes. 307 308 309 Functional characterization of parity-associated gene sets 310 To identify molecular pathways associated with the different parity modes we 311 performed separate functional enrichment analyses on the parity-associated genes sets 312 identified using differential expression and WGCNA analyses, using the PANTHER 313 classification tool32. Gene Set Enrichment Analyses (GSEAs)20 were used to identify 314 significantly enriched pathways for DEG gene sets using ranked expression scores (-log10(p- 315 value)*log2FoldChange) to calculate enrichment scores. To identify pathways that were 316 enriched within parity-associated co-expression modules, we performed individual Over- 317 Representation Analyses (ORAs) for each module. The background gene set for all GSEA 318 and ORA analyses was specified as the full set of 21,187 genes present within the genome8.

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319 P-values obtained for enrichment analyses were adjusted for multiple testing using 320 Bonferroni correction (FDR < 0.05). 321 322 Developmental pathways between parity modes across vertebrates 323 We first assessed the overlap between differentially expressed genes in systems with 324 oviparous-viviparous species pairs33,34. This included two lizard systems, the bimodal system 325 in Saiphos equalis and oviparous-viviparous sister species in the genus Phrynocepahlus. We 326 also extracted all genes that were differentially expressed between oviparous and viviparous 327 Zootoca vivipara during reproductive stages. This resulted in three lists of gene symbols – 328 one for each oviparous-viviparous model – between which we then assessed the overlap 329 using the R package ‘SuperExactTest’35. We assumed a total gene set equaling 20,000 genes, 330 which is a good approximation across genomes of vertebrate species36. We then performed 331 statistical tests to assess if intersections between gene sets were larger than expected by 332 change for each possible intersection as implemented in the package ‘SuperExactTest’. 333 In addition, we compiled a dataset that was composed of differentially expressed 334 genes in reproductive tissues of pregnant viviparous vertebrate species relative to their non- 335 pregnant states (Supplementary Table 21). This included the mammalian species Bos taurus 336 (cow), Capra aegagrus (goat), Canis lupus (wolf), Equus caballus (horse), Homo sapiens 337 (human), Monodelphis domestica (opossum) and Sus scrofa (boar). Gene sets of the three 338 more closely related even-toed ungulates (Bos taurus, Capra aegagrus, and Sus scrofa) were 339 combined into a single gene set. In addition, we included data on squamate species consisting 340 of the three gene sets from the previously extracted DE genes in the three bimodal lizard 341 systems (genes differentially expressed during pregnancy, excluding DE gene during non- 342 pregnant state), and the two independently derived viviparous species Chalcides ocellatus 343 and Pseudemoia entrecasteauxii within the family of skinks. Finally, we included 344 differentially expressed genes in the seahorse Hippocampus abdominalis (Supplementary 345 Table 21). The final data set consisted of 11 gene sets (five mammalian, five squamate and 346 one fish) composed of 13 species spanning amniotes and anamiote. Intersections between 347 gene sets were assessed in the same way as the previous analysis using the R package 348 ‘SuperExactTest’35. We performed three comparisons: i) overlap of genes across mammalian 349 gene sets, ii) overlap of genes across viviparous squamate gene sets, iii) overlap of genes 350 across all vertebrate viviparous gene sets. For genes that were shared by more than four 351 groups within the mammalian gene set and the squamate gene set we performed enrichment 352 analyses of biological pathways in WebGestalt20.

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353 Supplementary Table 1. List of individuals used for whole genome-resequencing. The 354 number of reads per individual and its respective coverage depth is provided. 355 ID reads depth

ELT03772 80427978 4.281 ELT03797 64296130 3.270 ELT04803 85009250 4.598 ELT04806 68865528 4.068 ELT04807 68454642 3.862 ELT04888 75063042 4.018 ELT04889 79356370 4.129 ELT04914 94843008 5.182 ELT04920 70621984 3.808 ELT04921 70377792 3.597 ELT04926 73862492 4.418 ELT04940 57037344 3.268 ELT04942 67684598 4.164 ELT04950 52574112 3.048 ELT04951 39290234 2.164 ELT04960 65645558 3.790 ELT04983 81561114 4.512 ELT05032 89824074 5.140 ELT07019 73446112 4.356 ELT07026 73053332 4.313 ELT07041 64714454 4.001 ELT07043 55312784 3.094 ELT07049 74720708 4.423 ELT07065 68645448 3.296 ELT07069 63861040 3.517 ELT07074 66470468 3.917 ELT07112 69014964 3.748 ELT07133 75760086 4.525 ELT07145 76375776 4.076 ELT07174 46037468 2.283 ELT07223 67651714 3.769 ELT07234 40361576 2.235 ELT07245 75520004 4.099 ELT07253 78107762 4.216 ELT07274 70431834 3.799 ELT07325 72376350 4.578 ELT07327 84693956 5.070 ELT07328 72897842 4.591 ELT08461 85676234 3.941

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ELT08465 73761084 4.274 ELT08472 76788824 4.211 ELT08474 66349514 4.063 ELT08476 67141510 3.560 ELT08478 64204634 3.364 ELT08479 74000664 4.081 ELT08480 79666560 4.511 ELT08484 77309548 4.788 ELT08494 81462106 4.971 ELT08506 84725226 4.973 ELT08512 82734322 4.924 ELT08523 75592812 4.438 ELT08547 81352552 4.648 ELT08552 62934160 3.445 ELT08559 77234594 4.767 ELT08564 69511596 4.166 ELT08567 81470842 3.897 ELT08569 79662392 4.235 ELT08578 67989526 4.092 ELT08580 106143904 6.177 ELT08588 45134330 2.617 ELT08605 84057326 4.706 ELT08608 86250284 4.924 ELT08625 94493732 5.367 ELT08640 84220588 2.606 ELT08653 73571734 4.543 356 357

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358 Supplementary Table 2. Bayesian sparse linear mixed model (BSLMM) results for the two 359 parity mode phenotypes a) gestation time and b) eggshell characteristics. Both traits were 360 highly heritable (h) and showed a large proportion of phenotypic variance explained by 361 genotypes (PVE) and sparse effects (PGE). 362 parameter mean median 2.50% 97.50%

a) gestation time h 0.958 0.967 0.873 0.992 PVE 0.971 0.971 0.957 0.983 rho 0.962 0.972 0.866 0.997 PGE 0.944 0.975 0.72 0.998

b) eggshell characteristics h 0.941 0.944 0.895 0.97 PVE 0.975 0.975 0.964 0.983 rho 0.995 0.997 0.979 1 PGE 0.998 0.999 0.989 1 363 364

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365 366 Supplementary Table 3. Genomic location of SNPs significantly associated with parity 367 mode phenotypes. Shown is each SNP showing significant association (adjusted P-value < 368 0.01) with either gestation time or eggshell characteristics. 369 adjusted P- adjusted allele allele allele P-value P-value chr Pos value P-value 1 0 freq. gestation eggshell gestation eggshell 1 27678198 G C 0.519 0.000001 0.000469 0.028000 0.597906 1 37901876 A G 0.390 0.023400 0.557588 0.000000 0.002376 1 37901881 A C 0.390 0.023400 0.557588 0.000000 0.002376 1 37901924 G C 0.396 0.014200 0.456527 0.000001 0.004296 1 38732877 A T 0.452 0.000000 0.000331 0.026900 0.590994 1 39565287 C G 0.448 0.000001 0.000685 0.000118 0.073304 1 44080709 C A 0.467 0.000000 0.000376 0.000074 0.064728 1 44772143 C T 0.455 0.000709 0.094545 0.000000 0.002017 1 45204754 C T 0.448 0.533000 0.979659 0.000001 0.004296 1 45591382 C T 0.467 0.000000 0.000166 0.000007 0.018992 1 45653230 G A 0.470 0.000000 0.000132 0.000017 0.033066 1 54174363 G A 0.479 0.000003 0.002148 0.001240 0.195055 1 55529635 T C 0.486 0.000000 0.000236 0.000099 0.070524 1 76723987 C T 0.480 0.000000 0.000270 0.121000 0.858846 1 76724038 G A 0.480 0.000000 0.000270 0.121000 0.858846 1 102229010 G A 0.473 0.000015 0.006509 0.007930 0.401455 1 106349594 A G 0.484 0.000001 0.000670 0.064300 0.752399 1 106349608 G A 0.484 0.000001 0.000670 0.064300 0.752399 1 110787939 G T 0.455 0.000004 0.002659 0.008460 0.408789 1 116097948 G C 0.450 0.000001 0.000670 0.634000 0.999316 1 116097963 T C 0.450 0.000001 0.000670 0.634000 0.999316 2 8355035 C A 0.489 0.000000 0.000074 0.000062 0.057507 2 10273275 C T 0.439 0.000332 0.057002 0.000000 0.000062 2 10700105 G A 0.455 0.000000 0.000339 0.001300 0.199439 2 11653201 G A 0.463 0.000001 0.000847 0.072500 0.775717 2 12085043 T A 0.448 0.000000 0.000074 0.042100 0.670741 2 12085066 T C 0.448 0.000000 0.000074 0.042100 0.670741 2 12085099 A G 0.448 0.000000 0.000074 0.042100 0.670741 2 15613643 C T 0.474 0.000000 0.000002 0.004080 0.304752 2 15613677 G A 0.475 0.000000 0.000005 0.005480 0.346020 2 15632780 C T 0.450 0.000015 0.006606 0.000023 0.037054 2 15758601 A G 0.449 0.000014 0.006292 0.000101 0.070524 2 16366687 T C 0.458 0.000550 0.081586 0.000000 0.002766 2 19793580 C A 0.470 0.000000 0.000046 0.028600 0.601644 2 20947944 A G 0.469 0.000000 0.000073 0.000027 0.038025 2 41781143 T C 0.460 0.000008 0.003969 0.000027 0.038025 2 42614456 G A 0.463 0.000001 0.000483 0.000007 0.018992

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2 61858188 G A 0.514 0.000021 0.008637 0.164000 0.912196 3 11749843 G A 0.453 0.000019 0.008027 0.035200 0.642938 3 20417670 C T 0.459 0.000000 0.000123 0.000000 0.000000 3 20431416 T C 0.459 0.000000 0.000123 0.000000 0.000000 3 22482441 T A 0.454 0.000011 0.005252 0.008040 0.402979 3 35809542 T C 0.475 0.000001 0.000847 0.004330 0.305847 3 35852320 C G 0.465 0.000587 0.085349 0.000001 0.007464 3 86066222 T C 0.511 0.000005 0.002978 0.003970 0.301093 5 477090 G T 0.442 0.000022 0.008877 0.254000 0.972241 5 17270575 C G 0.469 0.000021 0.008637 0.016500 0.512109 5 19308406 T C 0.506 0.000009 0.004543 0.005900 0.351370 5 55007878 T C 0.458 0.000025 0.009530 0.048800 0.699213 5 55007910 A G 0.458 0.000025 0.009530 0.048800 0.699213 5 55007918 C T 0.458 0.000025 0.009530 0.048800 0.699213 5 55007919 C G 0.458 0.000025 0.009530 0.048800 0.699213 5 55007922 G A 0.458 0.000025 0.009530 0.048800 0.699213 5 55356282 C T 0.463 0.000000 0.000027 0.004740 0.321428 5 55390057 C T 0.458 0.000001 0.000506 0.069600 0.769006 5 63125607 A C 0.496 0.000000 0.000060 0.000812 0.157892 5 63253432 A G 0.462 0.000025 0.009530 0.027500 0.595423 6 27637687 T C 0.504 0.000015 0.006509 0.000779 0.153697 7 12653261 C A 0.462 0.000019 0.008028 0.051700 0.710004 7 12653296 A G 0.462 0.000019 0.008028 0.051700 0.710004 7 12709349 G A 0.483 0.000000 0.000074 0.000171 0.087253 7 12784124 A G 0.460 0.000004 0.002659 0.027000 0.592707 7 33898157 A G 0.459 0.000000 0.000203 0.048500 0.698012 7 33898166 C T 0.459 0.000000 0.000203 0.048500 0.698012 7 33936114 G A 0.460 0.000000 0.000218 0.030000 0.614125 7 34009419 A C 0.478 0.000000 0.000001 0.000444 0.136516 7 34009427 C T 0.478 0.000000 0.000001 0.000444 0.136516 7 34044970 T C 0.511 0.000000 0.000000 0.000476 0.138222 7 43086030 A G 0.459 0.000011 0.005348 0.006560 0.365133 7 43138449 G A 0.468 0.000000 0.000000 0.000239 0.103690 7 43138501 C T 0.468 0.000000 0.000000 0.000239 0.103690 7 43181295 A G 0.454 0.000001 0.000433 0.000013 0.029051 7 43181374 C A 0.457 0.000000 0.000000 0.000000 0.000001 7 43181379 C T 0.457 0.000000 0.000000 0.000000 0.000001 8 3610551 A G 0.452 0.000016 0.007115 0.054300 0.718327 8 3970464 A T 0.480 0.000010 0.004842 0.016000 0.506328 8 4025501 C T 0.453 0.000000 0.000257 0.000016 0.032899 8 4888516 A G 0.459 0.000000 0.000017 0.012900 0.468487 8 28398646 G A 0.484 0.000001 0.000670 0.337000 0.994280 8 28398663 T A 0.486 0.000000 0.000000 0.029700 0.611552

13

8 28398680 T C 0.484 0.000001 0.000670 0.337000 0.994280 8 28398699 A G 0.484 0.000001 0.000670 0.337000 0.994280 8 32115550 G A 0.490 0.000000 0.000017 0.012200 0.458116 8 32115560 A C 0.489 0.000000 0.000000 0.005090 0.334865 8 32284966 A G 0.259 0.000013 0.005797 0.040500 0.665212 8 32285027 G A 0.259 0.000013 0.005797 0.040500 0.665212 8 32886588 G C 0.479 0.000000 0.000163 0.012200 0.458116 8 32886596 A G 0.479 0.000000 0.000163 0.012200 0.458116 8 32886635 G A 0.479 0.000000 0.000163 0.012200 0.458116 8 33254615 A C 0.259 0.000000 0.000383 0.006660 0.367854 8 33759119 A G 0.259 0.000000 0.000000 0.008260 0.404951 8 33969756 T C 0.483 0.000000 0.000051 0.002300 0.248129 8 33969768 G A 0.483 0.000000 0.000051 0.002300 0.248129 8 34166254 T C 0.473 0.000011 0.005333 0.000548 0.138336 8 34531398 A G 0.480 0.000008 0.003969 0.024900 0.578383 8 34531449 T C 0.480 0.000008 0.003969 0.024900 0.578383 8 34531459 C G 0.480 0.000008 0.003969 0.024900 0.578383 8 34575937 T C 0.481 0.000008 0.003969 0.132000 0.871818 8 34575959 G A 0.481 0.000008 0.003969 0.132000 0.871818 8 34575973 G A 0.481 0.000008 0.003969 0.132000 0.871818 8 35690660 A C 0.259 0.000001 0.000448 0.216000 0.953864 8 35798434 C T 0.489 0.000000 0.000339 0.079900 0.794628 8 36076269 A G 0.264 0.000001 0.000561 0.279000 0.979516 8 39967799 C T 0.264 0.000000 0.000025 0.405000 0.999316 8 39985699 T G 0.258 0.000000 0.000023 0.345000 0.997890 8 39985709 C A 0.258 0.000000 0.000023 0.345000 0.997890 8 39985757 T C 0.258 0.000000 0.000023 0.345000 0.997890 8 40867087 G A 0.264 0.000000 0.000000 0.146000 0.888307 8 42683231 A G 0.262 0.000000 0.000002 0.002580 0.253897 8 45095403 C T 0.258 0.000013 0.006098 0.096800 0.827476 8 48334915 G A 0.484 0.000000 0.000035 0.121000 0.858846 8 48838195 C G 0.262 0.000005 0.002921 0.456000 0.999316 8 51473733 T G 0.257 0.000024 0.009454 0.107000 0.841977 8 52118475 T C 0.262 0.000000 0.000026 0.133000 0.873063 8 55891326 T C 0.238 0.000000 0.000003 0.035500 0.643032 8 60068071 A G 0.261 0.000000 0.000351 0.170000 0.916694 8 60068082 T A 0.261 0.000000 0.000351 0.170000 0.916694 8 60068092 G A 0.261 0.000000 0.000351 0.170000 0.916694 8 60068113 T G 0.261 0.000000 0.000351 0.170000 0.916694 8 61054269 T G 0.476 0.000009 0.004312 0.399000 0.999316 8 61054298 T C 0.476 0.000009 0.004312 0.399000 0.999316 8 61054328 C T 0.476 0.000009 0.004312 0.399000 0.999316 8 61060792 T C 0.257 0.000010 0.005025 0.062000 0.745071

14

8 62681638 G C 0.262 0.000000 0.000070 0.026500 0.587925 8 63817209 G A 0.493 0.000000 0.000051 0.006420 0.363440 8 69068927 C T 0.462 0.000011 0.005188 0.000122 0.074022 8 70384414 T A 0.233 0.000004 0.002207 0.666000 0.999316 8 70384428 C A 0.238 0.000000 0.000000 0.047100 0.691932 8 70384453 G A 0.239 0.000001 0.000847 0.183000 0.927771 8 79099785 A G 0.511 0.000000 0.000031 0.110000 0.845145 8 83716265 C T 0.238 0.000000 0.000001 0.127000 0.867185 8 94687721 A G 0.483 0.000000 0.000047 0.169000 0.915523 8 94687798 C T 0.483 0.000000 0.000047 0.169000 0.915523 8 96694410 C T 0.478 0.000000 0.000123 0.641000 0.999316 8 96724165 C T 0.480 0.000000 0.000000 0.113000 0.850224 8 96771817 G A 0.478 0.000000 0.000123 0.641000 0.999316 8 97513051 A T 0.464 0.000004 0.002638 0.521000 0.999316 8 97513078 C T 0.476 0.000000 0.000000 0.008040 0.402979 9 35968002 C G 0.243 0.000001 0.000670 0.945000 0.999316 9 35968041 A G 0.243 0.000001 0.000670 0.945000 0.999316 9 35968053 C A 0.243 0.000001 0.000670 0.945000 0.999316 10 5811768 C G 0.476 0.000004 0.002584 0.552000 0.999316 10 16772540 C T 0.234 0.000011 0.005316 0.474000 0.999316 10 38503317 T C 0.467 0.000009 0.004483 0.000715 0.151041 10 42133960 C G 0.509 0.000013 0.006041 0.018500 0.529061 10 42687148 T C 0.333 0.615000 0.990021 0.000001 0.004894 10 45186089 A G 0.450 0.000000 0.000159 0.001360 0.205134 11 252272 C T 0.458 0.066600 0.751238 0.000002 0.008687 11 1141310 C T 0.444 0.000022 0.008953 0.109000 0.844376 11 20494249 C A 0.464 0.000000 0.000000 0.000115 0.073071 11 26712554 G A 0.450 0.000008 0.003969 0.024300 0.573031 11 26712576 A C 0.450 0.000008 0.003969 0.024300 0.573031 11 26712594 A G 0.450 0.000008 0.003969 0.024300 0.573031 11 26712603 A C 0.450 0.000008 0.003969 0.024300 0.573031 11 26712607 T C 0.450 0.000008 0.003969 0.024300 0.573031 11 29579573 G A 0.485 0.000002 0.001289 0.003020 0.272293 11 33283843 G C 0.462 0.000000 0.000125 0.000029 0.038025 13 17764338 T A 0.467 0.000001 0.000847 0.014900 0.494803 13 24311013 C T 0.458 0.000016 0.006885 0.000357 0.124502 13 24311045 G A 0.458 0.000016 0.006885 0.000357 0.124502 13 24855715 C T 0.459 0.000000 0.000163 0.000011 0.027853 13 30896909 C T 0.455 0.000016 0.007110 0.000455 0.137516 13 31816411 T C 0.475 0.000005 0.002992 0.125000 0.863170 13 33765950 G C 0.458 0.000001 0.000847 0.005660 0.348740 13 33948401 G A 0.455 0.000000 0.000000 0.089800 0.813334 13 33948460 A G 0.455 0.000000 0.000000 0.089800 0.813334

15

13 34274703 A G 0.454 0.000020 0.008236 0.164000 0.912196 13 35307434 T C 0.473 0.000006 0.003431 0.046300 0.689213 13 37799542 G A 0.465 0.000018 0.007640 0.001130 0.185716 13 37829883 G A 0.431 0.000014 0.006392 0.556000 0.999316 13 45395093 T C 0.262 0.000000 0.000035 0.000880 0.165907 14 35357977 G A 0.485 0.000000 0.000276 0.042000 0.670339 14 35357996 T A 0.470 0.000000 0.000000 0.005140 0.335581 14 35358024 T C 0.485 0.000000 0.000276 0.042000 0.670339 14 38397683 A G 0.463 0.000000 0.000094 0.801000 0.999316 14 38397757 T C 0.463 0.000000 0.000094 0.801000 0.999316 14 43524417 T G 0.294 0.690000 0.993094 0.000000 0.002766 14 50019648 T C 0.470 0.000006 0.003452 0.033400 0.634176 14 53518920 T G 0.457 0.000001 0.000501 0.156000 0.904027 14 53619964 C T 0.473 0.000005 0.002978 0.192000 0.934985 14 55192728 G A 0.511 0.000000 0.000170 0.007900 0.400942 14 57119667 A T 0.511 0.000020 0.008399 0.290000 0.981840 14 57119674 C A 0.510 0.000000 0.000299 0.124000 0.862241 14 57119685 A G 0.511 0.000020 0.008399 0.290000 0.981840 14 62384855 A G 0.459 0.000006 0.003478 0.009510 0.423054 14 63361648 C G 0.470 0.000014 0.006402 0.000561 0.139164 15 24651849 A C 0.459 0.000020 0.008236 0.062000 0.745071 15 24974668 A C 0.467 0.000005 0.002749 0.004140 0.305492 15 25231136 T G 0.437 0.000005 0.002978 0.987000 0.999316 16 25346940 C T 0.440 0.000005 0.002978 0.238000 0.966443 16 33009028 A T 0.512 0.000000 0.000147 0.150000 0.895627 17 21047056 C T 0.509 0.000024 0.009454 0.051600 0.709597 19 17384619 A T 0.246 0.000003 0.001985 0.027100 0.593772 19 29171686 G A 0.470 0.000001 0.000821 0.013300 0.473635 unanc hored 2593023 G A 0.453 0.000000 0.000225 0.000001 0.005649 unanc hored 3695006 G T 0.471 0.000007 0.003637 0.012500 0.464411 unanc hored 58366 C T 0.509 0.000001 0.000800 0.322000 0.990530 unanc hored 1197370 G C 0.471 0.000008 0.003969 0.005540 0.347633 unanc hored 1628736 T C 0.454 0.000000 0.000276 0.000000 0.002017 unanc hored 2903 C T 0.478 0.000005 0.002978 0.300000 0.983258 unanc hored 24599 G A 0.475 0.000000 0.000000 0.132000 0.871818 unanc hored 9318 G A 0.488 0.000006 0.003126 0.750000 0.999316 unanc hored 42828 A T 0.396 0.000023 0.009308 0.000103 0.070524 unanc hored 5253 A G 0.225 0.000019 0.008027 0.891000 0.999316 unanc 3828 G A 0.474 0.000001 0.000636 0.691000 0.999316

16

hored unanc hored 4575 G A 0.476 0.000000 0.000000 0.161000 0.908281 unanc hored 1716 G C 0.439 0.000005 0.003073 0.181000 0.927069 unanc hored 1759 C G 0.449 0.000000 0.000003 0.090500 0.813334 unanc hored 573 T C 0.489 0.000000 0.000001 0.068900 0.767368 unanc hored 579 G A 0.489 0.000000 0.000001 0.068900 0.767368 unanc hored 591 A G 0.491 0.000000 0.000000 0.002800 0.264577 unanc hored 499 A G 0.464 0.000003 0.001985 0.019400 0.536323 unanc hored 525 G C 0.462 0.000000 0.000129 0.013400 0.475100 unanc hored 7745 T C 0.261 0.000007 0.003832 0.821000 0.999316 unanc hored 45 C T 0.483 0.000000 0.000000 0.207000 0.945656 unanc hored 778 C T 0.458 0.000018 0.007638 0.642000 0.999316 unanc hored 802 A C 0.464 0.000000 0.000055 0.036200 0.646568 unanc hored 803 A C 0.459 0.000000 0.000062 0.154000 0.902835 unanc hored 206 G A 0.498 0.000002 0.000984 0.009270 0.422390 unanc hored 214 T C 0.452 0.000021 0.008479 0.010900 0.437170 unanc hored 225 C T 0.498 0.000002 0.000984 0.009270 0.422390 370 371

17

372 Supplementary Table 4. Pathways that were enriched for genes associated with parity mode 373 phenotypes. Significantly enriched (P < 0.05) pathways are shown with P-values in bold. 374 P- Description Size Expect Ratio FDR Value Alzheimer disease-presenilin pathway 30 0.996 6.03 0.0002 0.012 Wnt signalling pathway 67 2.224 3.15 0.0028 0.100 Cadherin signalling pathway 38 1.261 3.96 0.0052 0.123 T cell activation 18 0.597 5.02 0.0179 0.318 FAS signalling pathway 8 0.265 7.53 0.0257 0.365 Huntington disease 40 1.327 3.01 0.0352 0.416 Nicotinic acetylcholine receptor signalling pathway 25 0.830 3.62 0.0438 0.430 Cytoskeletal regulation by Rho GTPase 26 0.863 3.48 0.0485 0.430 Alzheimer disease-amyloid secretase pathway 16 0.531 3.77 0.0943 0.744 Inflammation mediated by chemokine and cytokine 41 1.361 2.20 0.1465 0.968 signalling pathway 375 376

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377 Supplementary Table 5. Biological processes that were significantly enriched (P < 0.01) for 378 genes that showed association with gestation time. 379 P - Description Size Expect Ratio FDR Value response to growth factor 253 7.9 2.0 0.005 0.518 positive regulation of cell death 188 5.9 2.2 0.006 0.518 positive regulation of cell proliferation 302 9.4 1.9 0.006 0.518 negative regulation of cell proliferation 211 6.6 2.1 0.006 0.518 regulation of cell cycle 390 12.1 1.7 0.010 0.567 cell junction organization 96 3.0 2.7 0.010 0.567 380 381 382 383

19

384 Supplementary Table 6. Biological processes that were significantly enriched (P < 0.01) for 385 genes that showed association with eggshell traits. 386 P - Description Size Expect Ratio FDR Value negative regulation of cell communication 477 1.7 4.6 0.0002 0.032 negative regulation of signaling 478 1.7 4.6 0.0002 0.032 cytokine production 201 0.7 6.9 0.0007 0.076 positive regulation of catalytic activity 473 1.7 3.5 0.0057 0.436 taxis 209 0.8 5.3 0.0063 0.436 negative regulation of molecular function 362 1.3 3.8 0.0086 0.496 387 388 389 390

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391 Supplementary Table 7. Samples collected for RNA sequencing and their respective stages 392 during gestation. Sequencing effort for each sample with raw reads, filtered reads and the 393 percentage of reads that mapped to the Zootoca vivipara reference genome are shown. 394 Number of % Sampling parity eggs Number of ID stage cleaned reads date mode (N) raw reads reads mapped ELT08543 08/06/2017 early oviparous 6 57,387,536 34,089,830 56.64 ELT08544 08/06/2017 early oviparous 8 62,201,602 23,813,398 40.24 ELT08593 08/06/2017 early oviparous 10 57,719,308 56,257,371 67.01 ELT08526 08/06/2017 early viviparous 8 45,203,318 42,765,373 74.38 ELT08527 08/06/2017 early viviparous 6 45,000,467 40,536,529 76.75 ELT08528 08/06/2017 early viviparous 8 51,547,225 40,609,297 73.42 ELT08628 18/06/2017 mid oviparous 6 47,401,105 40,848,251 76.31 ELT08630 20/06/2017 mid oviparous 5 22,574,287 14,278,997 70.59 ELT08545 18/06/2017 mid oviparous 11 48,494,343 16,327,194 74.48 ELT08529 18/06/2017 mid viviparous 3 16,276,083 8,761,328 69.16 ELT08532 18/06/2017 mid viviparous 5 43,348,318 35,674,242 74.37 ELT08534 18/06/2017 mid viviparous 5 42,335,556 36,759,557 74.96 ELT08636 15/07/2017 after oviparous 4 65,425,714 64,720,844 75.01 ELT08637 07/07/2017 after oviparous 6 44,968,452 40,268,336 71.36 ELT08638 30/06/2017 after oviparous 8 53,914,941 50,105,353 71.53 ELT08585 16/07/2017 after viviparous 4 66,889,404 61,662,615 61.83 ELT08533 09/07/2017 after viviparous 8 66,889,404 40,315,756 77.27 ELT08659 16/07/2017 after viviparous 8 66,889,404 48,301,789 80.10 395

21

396 Supplementary Table 8. Pathways were enriched for differentially expressed (DE) genes 397 between oviparous and viviparous common lizards during reproductive stages (N = 2160 398 genes). Significantly enriched (P < 0.05) pathways are shown with P-values in bold. 399 P - Description Size Expect Ratio FDR Value

Apoptosis signaling pathway 21 2.93 2.39 0.017 0.65 Parkinson disease 26 3.62 2.21 0.018 0.65 Alzheimer disease-amyloid secretase pathway 16 2.23 2.24 0.057 1.00 Angiogenesis 46 6.41 1.56 0.087 1.00 B cell activation 11 1.53 1.96 0.188 1.00 Metabotropic glutamate receptor group I pathway 6 0.84 2.39 0.198 1.00 Axon guidance mediated by semaphorins 6 0.84 2.39 0.198 1.00 p38 MAPK pathway 6 0.84 2.39 0.198 1.00 TGF-beta signaling pathway 29 4.04 1.48 0.203 1.00 VEGF signaling pathway 20 2.79 1.43 0.299 1.00 400 401 402 403

22

404 Supplementary Table 9. Pathways that were enriched for genes associated with 405 overexpression in viviparous and oviparous modules (P < 0.05) identified from a Weighted 406 Gene Co-Expression Network Analysis (WGCNA). 407 P - Description Size Expect Ratio FDR Value

Parity DarkGreen Module - up-regulated in viviparous Angiogenesis 44 3.47 2.0 0.045 1.0 Parity LightCyan Module - up-regulated in viviparous Beta2 adrenergic receptor signaling pathway 7 0.33 6.0 0.039 0.59 Beta1 adrenergic receptor signaling pathway 7 0.33 6.0 0.039 0.59 VEGF signaling pathway 18 0.86 3.5 0.048 0.59 Parity DarkRed Module - up-regulated in oviparous TGF-beta signaling pathway 27 0.26 7.8 0.022 1.0 408 409

23

410 Supplementary Table 10. List of all hub genes with genomic location in the Zootoca vivipara genome, the chicken Ensembl ID for reference 411 and the gene symbol. 412 start end transcript chicken gene chromosome position position ID Enseml ID symbol

1 45378832 45378892 evm.TU.Contig109.17 ENSGALP00000064984.1 HTR4 1 63590103 63590189 evm.TU.Contig113.129 ENSGALP00000019941.5 TSPAN5 2 9850320 9850339 evm.TU.Contig19.237 ENSGALP00000040485.3 KANK3 2 9976689 10013387 evm.TU.Contig19.242 ENSGALP00000056791.2 KCNN1 2 10109211 10128500 evm.TU.Contig19.246 ENSGALP00000051498.2 not annotated 2 33832162 33837231 evm.TU.Contig4.344 NA not annotated 2 59660885 59669261 evm.TU.Contig32.38 ENSGALP00000048311.1 FOXF1 3 15287319 15297959 evm.TU.Contig56_17535_7198940.45 ENSGALP00000018320.4 DLK1 3 80713623 80729999 evm.TU.Contig44_1_17822621.204 ENSGALP00000067370.1 RAB15 3 81052623 81119154 evm.TU.Contig44_1_17822621.193 ENSGALP00000018192.5 not annotated 3 84816347 84838354 evm.TU.Contig44_1_17822621.95 ENSGALP00000018780.7 CYP27C1 3 87211117 87364319 evm.TU.Contig44_1_17822621.73 ENSGALP00000018975.4 GLI2 3 130612659 130612829 evm.TU.Contig122.27 ENSGALP00000012115.5 KMO 3 131264813 131264953 evm.TU.Contig122.45 ENSGALP00000006787.2 TWIST2 4 382314 382467 evm.TU.Contig179_607731_877028.10 ENSGALP00000007657.4 EPB42 4 49430261 49435985 evm.TU.Contig94_1_8959079.49 ENSGALP00000055864.1 B4GALT2 4 49554981 49567789 evm.TU.Contig94_1_8959079.45 ENSGALP00000068274.1 not annotated 4 50732426 50784018 evm.TU.Contig94_1_8959079.12 ENSGALP00000016460.4 PTCH2 4 65299681 65299743 evm.TU.Contig48.117 ENSGALP00000014437.5 ADGRL4 5 87849389 87849475 evm.TU.Contig17.192 ENSGALP00000026283.2 GSTAL3 6 5214019 5247082 evm.TU.Contig29_1_11038465.149 ENSGALP00000057931.2 TBX2 6 12090716 12109729 evm.TU.Contig62.18 ENSGALP00000002144.5 SPNS3

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6 21045084 21082587 evm.TU.Contig62.195 ENSGALP00000002228.5 JAM3 6 33030313 33118194 evm.TU.Contig45_1_13152689.192 ENSGALP00000024287.3 IGSF11 6 34737928 34755516 evm.TU.Contig45_1_13152689.218 ENSGALP00000048818.2 CAPG 7 15222947 15235275 evm.TU.Contig20.106 NA not annotated 7 27436887 27537577 evm.TU.Contig20.250 ENSGALP00000022341.2 CDH7 7 33517569 33517763 evm.TU.Contig129_1_5041412.53 ENSGALP00000045407.2 DTNA 8 10547974 10584121 evm.TU.Contig25.91 ENSGALP00000062725.2 not annotated 8 39774752 39774772 evm.TU.Contig18.171 ENSGALP00000050144.1 RAPGEF2 8 69033444 69034019 evm.TU.Contig176_1_490717.11 ENSGALP00000008781.1 RHOGL 8 84895951 84895996 evm.TU.Contig166_1_2019166.14 ENSGALP00000034251.4 STOM 8 98130892 98139194 evm.TU.Contig288_1_630801.21 ENSGALP00000014077.2 CXorf56 9 22687617 22729762 evm.TU.Contig79.122 ENSGALP00000074302.1 EHBP1 9 33648065 33702978 evm.TU.Contig58_1_7040991.247 ENSGALP00000047227.2 not annotated 10 11828924 11829005 evm.TU.Contig105_1_3782555.104 ENSGALP00000067180.1 not annotated 10 25292721 25325721 evm.TU.Contig61.70 ENSGALP00000051180.2 not annotated 10 30176526 30176594 evm.TU.Contig126_1_3591689.52 ENSGALP00000011048.6 TSPAN4 10 30695305 30695397 evm.TU.Contig126_1_3591689.29 ENSGALP00000056156.1 DHDH 11 916329 919040 evm.TU.Contig189.46 ENSGALP00000045233.2 NUDT16L1 11 8716599 8716652 evm.TU.Contig5_1_18034934.164 ENSGALP00000010735.5 ABCC1 11 25691558 25691937 evm.TU.Contig135.4 ENSGALP00000033333.5 SLCO3A1 11 28640291 28640362 evm.TU.Contig135.64 ENSGALP00000052626.2 UACA 11 29647256 29647411 evm.TU.Contig135.113 ENSGALP00000013709.6 MAP1A 11 31337984 31344995 evm.TU.Contig8.393 ENSGALP00000011318.5 NR2F2 12 7055438 7086045 evm.TU.Contig36.37 ENSGALP00000008350.3 AQP1 13 53040084 53110957 evm.TU.Contig33.234 ENSGALP00000026036.6 PDE9A 13 67708626 67723820 evm.TU.Contig22_1_3128639.43 ENSGALP00000026829.3 not annotated

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13 96676828 96715575 evm.TU.Contig153_1_955746.3 ENSGALP00000074104.1 PCDH17 14 53882063 53906721 evm.TU.Contig3_1_22572018.214 ENSGALP00000072326.1 CACNA1C 14 64935354 64954239 evm.TU.Contig3_1_22572018.77 ENSGALP00000043945.1 SLC35B4 15 3683671 3729652 evm.TU.Contig65.59 ENSGALP00000022924.4 PARVB 15 9454425 9621443 evm.TU.Contig46.104 ENSGALP00000009939.8 not annotated 16 19830342 19855567 evm.TU.Contig39_1_12749897.83 ENSGALP00000023718.6 not annotated 16 31978878 31979236 evm.TU.Contig163.43 ENSGALP00000063846.2 RPL6 17 14952214 14997310 evm.TU.Contig6_1_33087639.8 ENSGALP00000058318.1 NPR3 19 8356440 8477207 evm.TU.Contig2_1_35850901.494 ENSGALP00000046258.2 SLIT2 19 43762442 43767591 evm.TU.Contig5_1_18034934.308 ENSGALP00000014949.4 NMUR1 not anchored NA NA evm.TU.Contig3448.1 ENSGALP00000073489.1 CPAMD8 not anchored NA NA evm.TU.Contig334_56644_339995.5 ENSGALP00000054475.1 LTB4R not anchored NA NA evm.TU.Contig14674.1 NA not annotated not anchored NA NA evm.TU.Contig49_1_4228292.41 ENSGALP00000010368.6 PANK1 not anchored NA NA evm.TU.Contig1593.1 ENSGALP00000039140.2 PYGB not anchored NA NA evm.TU.Contig584_1_30145.2 ENSGALP00000050924.2 TMEM101 413

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414 415 Supplementary Table 11. Enrichment of all annotated hub genes (N = 51) for biological 416 processes (P < 0.01). 417 P - Description Size Expect Ratio FDR Value

establishment or maintenance of cell polarity 85 0.30 13.54 0.0002 0.065 Notch signaling pathway 77 0.27 11.21 0.0023 0.395 renal system process 29 0.10 19.84 0.0044 0.514 epithelium development 382 1.33 3.76 0.0089 0.617 biological adhesion 400 1.39 3.60 0.0107 0.622 second-messenger-mediated signaling 153 0.53 5.64 0.0153 0.653 protein localization to membrane 171 0.59 5.05 0.0206 0.653 418 419 420

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421 Supplementary Table 12. Pathways showing enrichment of genes (N = 1621) linked to 422 SNPs under selection (q < 0.01). Significantly enriched pathways (P < 0.05) are shown in 423 bold. 424 P - Description Size Expect Ratio FDR Value FAS signalling pathway 8 0.90 3.32 0.050 0.745 Angiogenesis 46 5.19 1.73 0.059 0.745 Cytoskeletal regulation by Rho GTPase 26 2.93 2.05 0.060 0.745 Oxidative stress response 9 1.02 2.95 0.070 0.745 Alzheimer disease-amyloid secretase pathway 16 1.81 2.22 0.094 0.745 De novo purine biosynthesis 5 0.56 3.55 0.100 0.745 EGF receptor signalling pathway 30 3.39 1.77 0.108 0.745 Cadherin signalling pathway 38 4.29 1.63 0.121 0.745 Nicotinic acetylcholine receptor signalling 25 2.82 1.77 0.138 0.745 pathway p38 MAPK pathway 6 0.68 2.95 0.139 0.745 425 426 427

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428 Supplementary Table 13. Overlap of genes differentially expressed between oviparous and 429 viviparous related squamate systems. All intersections are shown, and significant 430 intersections are shown in bold. All intersections were significant. 431 N genes N genes Intersections Degree FE P-value (shared) (expected) Zootoca 1 2150 NA NA NA Saiphos 1 605 NA NA NA Phrynocephalus 1 458 NA NA NA Saiphos & Zootoca 2 68 65 1.05 0.37 Phrynocephalus & Zootoca 2 99 49.2 2.01 <0.0001 Phrynocephalus & Saiphos 2 15 13.9 1.08 0.41 Phrynocephalus & Saiphos & Zootoca 3 8 1.5 5.37 <0.0001 432

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433 Supplementary Table 14. Overlap of DE genes shared by viviparous squamates during 434 pregnancy. All intersections are shown, and significant intersections are shown in bold. 435 N genes N genes Intersections Degree FE P-value (shared) (expected)

Zootoca 1 2150 NA NA NA Phrynocephalus 1 458 NA NA NA Chalcides 1 6602 NA NA NA Pseudemoia 1 2599 NA NA NA Saiphos 1 362 NA NA NA Chalcides & Zootoca 2 1011 709.7 1.42 <0.0001 Chalcides & Phrynocephalus 2 229 151.2 1.51 <0.0001 Pseudemoia & Zootoca 2 396 279.4 1.42 <0.0001 Pseudemoia & Chalcides 2 1025 857.9 1.19 <0.0001 Phrynocephalus & Zootoca 2 99 49.2 2.01 <0.0001 Pseudemoia & Phrynocephalus 2 85 59.5 1.43 0.0004 Saiphos & Zootoca 2 60 38.9 1.54 0.0004 Saiphos & Pseudemoia 2 64 47 1.36 0.0061 Saiphos & Chalcides 2 131 119.5 1.1 0.1078 Saiphos & Phrynocephalus 2 10 8.3 1.21 0.318 Pseudemoia & Chalcides & Zootoca 3 227 92.2 2.46 <0.0001 Chalcides & Phrynocephalus & Zootoca 3 48 16.3 2.95 <0.0001 Pseudemoia & Chalcides & Phrynocephalus 3 52 19.6 2.65 <0.0001 Pseudemoia & Phrynocephalus & Zootoca 3 27 6.4 4.22 <0.0001 Saiphos & Pseudemoia & Chalcides 3 42 15.5 2.7 <0.0001 Saiphos & Chalcides & Zootoca 3 36 12.8 2.8 <0.0001 Saiphos & Pseudemoia & Zootoca 3 15 5.1 2.97 0.0002 Saiphos & Pseudemoia & Phrynocephalus 3 5 1.1 4.64 0.0048 Saiphos & Phrynocephalus & Zootoca 3 4 0.9 4.49 0.0128 Saiphos & Chalcides & Phrynocephalus 3 6 2.7 2.19 0.0584 Pseudemoia & Chalcides & Phrynocephalus & Zootoca 4 17 2.1 8.05 <0.0001 Saiphos & Pseudemoia & Chalcides & Zootoca 4 13 1.7 7.79 <0.0001 Saiphos & Pseudemoia & Chalcides & Phrynocephalus 4 3 0.4 8.44 0.0057 Saiphos & Chalcides & Phrynocephalus & Zootoca 4 2 0.3 6.8 0.0355 Saiphos & Pseudemoia & Phrynocephalus & Zootoca 4 1 0.1 8.64 0.1094 Saiphos & Pseudemoia & Chalcides & Phrynocephalus & Zootoca 5 1 0 26.16 0.0375 436

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437 Supplementary Table 15. List of core differentially expressed (DE) genes between pregnant 438 and non-pregnant viviparous squamates. Only genes shared by at least four viviparous 439 squamates are shown. Presence of a DE gene is indicated by ‘1’, absence by ‘0’. 440 sum sum gene C. P. P. S. Z. shared all squamates symbol ocellatus vlangalii entrecasteauxii equalis vivipara excl. shared Zootoca CDH5 1 1 1 1 1 5 5 ELL2 1 0 1 1 1 4 6 RASEF 1 1 1 0 1 4 6 SGK1 1 0 1 1 1 4 6 RHOU 1 0 1 1 1 4 6 ASAH1 1 0 1 1 1 4 5 B4GALT3 1 0 1 1 1 4 5 EDEM3 1 1 1 0 1 4 5 ATP8B1 1 1 1 0 1 4 5 DIO2 1 1 1 1 0 4 6 COL4A2 1 0 1 1 1 4 5 KCNK1 1 1 1 0 1 4 5 MCOLN3 1 1 0 1 1 4 5 CTSA 1 0 1 1 1 4 5 PLCB4 1 1 1 0 1 4 5 SLC7A1 1 1 1 0 1 4 5 ATP8A1 1 1 1 0 1 4 4 ITPK1 1 1 1 0 1 4 4 CLCN3 1 1 1 0 1 4 4 SCNN1A 1 0 1 1 1 4 4 SLC38A2 1 1 1 0 1 4 4 SLC9A2 1 0 1 1 1 4 4 SMAD6 1 0 1 1 1 4 4 CYP51A1 1 1 1 1 0 4 5 B4GALNT3 1 1 1 0 1 4 4 ACVR2B 1 1 1 0 1 4 3 LMBRD2 1 1 1 0 1 4 3 NR4A2 1 0 1 1 1 4 3 PXDN 1 1 1 0 1 4 3 SCNN1B 1 0 1 1 1 4 3 SLC7A11 1 1 1 0 1 4 3 TMEM181 1 1 1 0 1 4 3 441

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442 Supplementary Table 16. Overlap of differentially expressed genes shared by viviparous 443 mammals during pregnancy. All intersections are shown, and significant intersections are 444 shown in bold. All intersections were significant. 445 N genes N genes Intersections Degree FE P-value (shared) (expected) Bos 1 5095 NA NA NA Canis 1 1439 NA NA NA Equus 1 342 NA NA NA Homo 1 2310 NA NA NA Monodelphis 1 2152 NA NA NA Bos & Homo 2 838 588.5 1.42 <0.0001 Monodelphis & Homo 2 418 248.6 1.68 <0.0001 Bos & Canis 2 545 366.6 1.49 <0.0001 Monodelphis & Bos 2 754 548.2 1.38 <0.0001 Bos & Equus 2 170 87.1 1.95 <0.0001 Monodelphis & Equus 2 86 36.8 2.34 <0.0001 Monodelphis & Canis 2 245 154.8 1.58 <0.0001 Equus & Homo 2 89 39.5 2.25 <0.0001 Equus & Canis 2 48 24.6 1.95 <0.0001 Canis & Homo 2 195 166.2 1.17 0.0087 Monodelphis & Bos & Homo 3 203 63.3 3.21 <0.0001 Monodelphis & Bos & Equus 3 53 9.4 5.65 <0.0001 Monodelphis & Bos & Canis 3 107 39.4 2.71 <0.0001 Bos & Equus & Homo 3 42 10.1 4.17 <0.0001 Monodelphis & Equus & Homo 3 27 4.3 6.35 <0.0001 Monodelphis & Canis & Homo 3 55 17.9 3.08 <0.0001 Bos & Canis & Homo 3 89 42.3 2.10 <0.0001 Bos & Equus & Canis 3 28 6.3 4.47 <0.0001 Equus & Canis & Homo 3 15 2.8 5.28 <0.0001 Monodelphis & Equus & Canis 3 13 2.6 4.91 <0.0001 Monodelphis & Bos & Equus & Homo 4 16 1.1 14.78 <0.0001 Monodelphis & Bos & Canis & Homo 4 26 4.6 5.71 <0.0001 Monodelphis & Equus & Canis & Homo 4 8 0.3 26.16 <0.0001 Monodelphis & Bos & Equus & Canis 4 8 0.7 11.86 <0.0001 Bos & Equus & Canis & Homo 4 8 0.7 11.05 <0.0001 Monodelphis & Bos & Equus & Canis & Homo 5 5 0.1 64.18 <0.0001 446 447

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448 Supplementary Table 17. List of core differentially expressed (DE) genes between pregnant 449 and non-pregnant viviparous mammals. Only genes shared by at least four viviparous 450 mammals are shown. Presence of a DE gene is indicated by ‘1’, absence by ‘0’. 451 sum gene M. E. caballus Artiodactyla C. lupus H. sapiens mammals symbol domestica shared UPK1B 1 1 1 1 1 5 CDO1 1 1 1 1 1 5 SLCO2A1 1 1 1 1 1 5 THBS2 1 1 1 1 1 5 FGL1 1 1 1 1 1 5 AR 0 1 1 1 1 4 ADAMTS1 0 1 1 1 1 4 PHGDH 1 1 1 0 1 4 CA12 0 1 1 1 1 4 CXCL14 0 1 1 1 1 4 GLUL 0 1 1 1 1 4 SLC1A1 0 1 1 1 1 4 TNC 0 1 1 1 1 4 DACT2 0 1 1 1 1 4 FLT1 0 1 1 1 1 4 IER3 1 1 1 1 0 4 PLXDC2 1 1 1 0 1 4 TACSTD2 1 1 1 0 1 4 GARNL3 1 1 1 0 1 4 GSN 1 1 1 0 1 4 PROCR 1 1 0 1 1 4 ATP6V0A4 1 0 1 1 1 4 ATP13A4 0 1 1 1 1 4 MFSD4 0 1 1 1 1 4 OAS3 0 1 1 1 1 4 PALMD 0 1 1 1 1 4 PCSK6 0 1 1 1 1 4 NOS3 0 1 1 1 1 4 TNFRSF12A 1 1 1 1 0 4 VLDLR 1 1 1 1 0 4 DMBT1 1 1 1 0 1 4 ENPP1 1 1 1 0 1 4 LTBP1 1 1 1 0 1 4 MET 1 1 1 0 1 4 SFRP1 1 1 0 1 1 4 RARRES2 1 0 1 1 1 4 ACSL5 0 1 1 1 1 4

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HLF 0 1 1 1 1 4 IGDCC4 0 1 1 1 1 4 KCNE3 0 1 1 1 1 4 OSMR 0 1 1 1 1 4 SLC39A14 0 1 1 1 1 4 CRYAB 1 1 1 0 1 4 GNAI1 1 1 1 0 1 4 CP 1 1 0 1 1 4 SERPINA1 1 0 1 1 1 4 452 453

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454 Supplementary Table 18. Enrichment of gene sets of genes that were shared by at least four 455 viviparous mammals for biological processes (P < 0.01). 456 Description Size Expect Ratio P Value FDR morphogenesis of a branching structure 196 0.54 9.21 0.0002 0.05 regulation of vasculature development 313 0.87 6.92 0.0002 0.05 response to antibiotic 316 0.87 6.86 0.0002 0.05 urogenital system development 326 0.90 6.65 0.0003 0.05 response to alcohol 231 0.64 7.82 0.0004 0.07 response to ketone 189 0.52 7.64 0.0018 0.20 regulation of supramolecular fiber organization 329 0.91 5.49 0.0020 0.20 angiogenesis 487 1.35 4.45 0.0021 0.20 positive regulation of cell motility 493 1.37 4.40 0.0022 0.20 response to toxic substance 499 1.38 4.34 0.0023 0.20 regulation of actin filament-based process 362 1.00 4.99 0.0031 0.21 extrinsic apoptotic signaling pathway 220 0.61 6.57 0.0031 0.21 transition metal ion transport 109 0.30 9.94 0.0034 0.21 epithelial cell proliferation 372 1.03 4.85 0.0035 0.21 regulation of apoptotic signaling pathway 385 1.07 4.69 0.0040 0.23 regulation of cellular response to growth factor stimulus 256 0.71 5.64 0.0053 0.28 sex differentiation 266 0.74 5.43 0.0061 0.30 reproductive system development 428 1.19 4.22 0.0063 0.30 gland development 434 1.20 4.16 0.0066 0.30 tissue migration 283 0.78 5.10 0.0076 0.30 trabecula morphogenesis 49 0.14 14.74 0.0081 0.30 cell chemotaxis 289 0.80 5.00 0.0082 0.30 negative regulation of transport 458 1.27 3.94 0.0083 0.30 positive regulation of response to external stimulus 293 0.81 4.93 0.0086 0.30 457 458

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459 Supplementary Table 19. Overlap of differentially expressed genes shared by viviparous 460 vertebrates during pregnancy. All intersections are shown, and significant intersections are 461 shown in bold. Abbreviations for genera are: Ho = Homo, Ca = Canis, Eq = Equus, Bo = Bos, 462 Mo = Monodelphis, Sa = Saiphos, Ps = Pseudemoia, Ch = Chalcides, Ph = Phrynocephalus, 463 Zo = Zootoca, Hi = Hippocampus. To facilitate interpretation of the table, the text for 464 mammals is in blue, squamates in green, seahorse in pink. 465

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ho 1 2310 NA NA NA Ca 1 1439 NA NA NA Eq 1 342 NA NA NA Bo 1 5095 NA NA NA Mo 1 2152 NA NA NA Sa 1 362 NA NA NA Ps 1 2599 NA NA NA Ch 1 6602 NA NA NA Ph 1 458 NA NA NA Zo 1 2150 NA NA NA Hi 1 311 NA NA NA Ph & Ps 2 85 59.5 1.43 0.0004 Zo & Sa 2 60 38.9 1.54 0.0004 Sa & Mo 2 60 39.0 1.54 0.0005 Zo & Ho 2 295 248.3 1.19 0.0006 Ph & Ho 2 76 52.9 1.44 0.0007 Hi & Ca 2 38 22.4 1.70 0.001 Hi & Bo 2 102 79.2 1.29 0.002 Ps & Eq 2 63 44.4 1.42 0.003 Ps & Sa 2 64 47.0 1.36 0.006 Hi & Mo 2 48 33.5 1.43 0.007 Ph & Mo 2 66 49.3 1.34 0.008 Ca & Ho 2 195 166.2 1.17 0.009 Sa & Bo 2 110 92.2 1.19 0.019 Sa & Ho 2 55 41.8 1.32 0.020 Ph & Eq 2 14 7.8 1.79 0.027 Ph & Ca 2 44 33.0 1.34 0.031 Hi & Ho 2 47 35.9 1.31 0.033 Hi & Ps 2 52 40.4 1.29 0.033 Sa & Eq 2 11 6.2 1.78 0.048 Hi & Eq 2 9 5.3 1.69 0.09 Hi & Ph 2 11 7.1 1.54 0.10 Ch & Sa 2 131 119.5 1.10 0.11 Hi & Zo 2 40 33.4 1.20 0.13

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N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Sa 2 8 5.6 1.42 0.20 Sa & Ca 2 30 26.0 1.15 0.23 Ph & Sa 2 10 8.3 1.21 0.32 Ch & Bo 2 2353 1681.9 1.40 <0.0001 Ps & Mo 2 540 279.7 1.93 <0.0001 Zo & Ch 2 1011 709.7 1.42 <0.0001 Bo & Ho 2 838 588.5 1.42 <0.0001 Mo & Ho 2 418 248.6 1.68 <0.0001 Bo & Ca 2 545 366.6 1.49 <0.0001 Mo & Bo 2 754 548.2 1.38 <0.0001 Zo & Bo 2 738 547.7 1.35 <0.0001 Bo & Eq 2 170 87.1 1.95 <0.0001 Ch & Ca 2 632 475.0 1.33 <0.0001 Ph & Bo 2 204 116.7 1.75 <0.0001 Ph & Ch 2 229 151.2 1.51 <0.0001 Zo & Ps 2 396 279.4 1.42 <0.0001 Mo & Eq 2 86 36.8 2.34 <0.0001 Mo & Ca 2 245 154.8 1.58 <0.0001 Eq & Ho 2 89 39.5 2.25 <0.0001 Ch & Ps 2 1025 857.9 1.19 <0.0001 Zo & Ph 2 99 49.2 2.01 <0.0001 Ch & Ho 2 907 762.5 1.19 <0.0001 Zo & Mo 2 326 231.3 1.41 <0.0001 Ps & Ho 2 404 300.2 1.35 <0.0001 Ps & Bo 2 784 662.1 1.18 <0.0001 Ch & Eq 2 163 112.9 1.44 <0.0001 Zo & Ca 2 213 154.7 1.38 <0.0001 Ps & Ca 2 244 187.0 1.30 <0.0001 Ch & Mo 2 802 710.4 1.13 <0.0001 Eq & Ca 2 48 24.6 1.95 <0.0001 Hi & Ch 2 139 102.7 1.35 <0.0001 Zo & Eq 2 61 36.8 1.66 <0.0001 Ch & Bo & Ho 3 441 194.3 2.27 <0.0001 Zo & Ch & Bo 3 408 180.8 2.26 <0.0001 Ch & Ps & Bo 3 452 218.6 2.07 <0.0001 Ps & Mo & Ho 3 143 32.3 4.43 <0.0001 Mo & Bo & Ho 3 203 63.3 3.21 <0.0001 Ps & Mo & Bo 3 204 71.2 2.86 <0.0001 Ch & Bo & Ca 3 278 121.0 2.30 <0.0001 Ps & Bo & Ho 3 206 76.5 2.69 <0.0001

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N genes N genes Intersections Degree FE P-value (shared) (expected)

Ch & Ps & Mo 3 229 92.3 2.48 <0.0001 Zo & Ch & Ps 3 227 92.2 2.46 <0.0001 Ch & Ps & Ho 3 225 99.1 2.27 <0.0001 Ch & Mo & Bo 3 334 181.0 1.85 <0.0001 Ch & Mo & Ho 3 184 82.0 2.24 <0.0001 Mo & Bo & Eq 3 53 9.4 5.65 <0.0001 Ch & Bo & Eq 3 91 28.8 3.16 <0.0001 Zo & Ps & Mo 3 97 30.1 3.23 <0.0001 Ph & Ch & Bo 3 108 38.5 2.80 <0.0001 Mo & Bo & Ca 3 107 39.4 2.71 <0.0001 Zo & Mo & Bo 3 138 58.9 2.34 <0.0001 Zo & Ps & Bo 3 156 71.2 2.19 <0.0001 Ch & Mo & Eq 3 53 12.1 4.36 <0.0001 Zo & Ch & Ho 3 170 82.0 2.07 <0.0001 Zo & Bo & Ho 3 142 63.3 2.24 <0.0001 Ch & Ps & Ca 3 138 61.7 2.24 <0.0001 Ch & Eq & Ho 3 53 13.0 4.06 <0.0001 Ps & Mo & Ca 3 64 20.1 3.18 <0.0001 Zo & Ch & Ca 3 114 51.1 2.23 <0.0001 Bo & Eq & Ho 3 42 10.1 4.17 <0.0001 Mo & Eq & Ho 3 27 4.3 6.35 <0.0001 Ps & Bo & Ca 3 105 47.6 2.20 <0.0001 Zo & Bo & Ca 3 92 39.4 2.33 <0.0001 Zo & Ch & Mo 3 145 76.4 1.90 <0.0001 Zo & Mo & Ho 3 71 26.7 2.66 <0.0001 Mo & Ca & Ho 3 55 17.9 3.08 <0.0001 Zo & Ch & Eq 3 42 12.1 3.46 <0.0001 Ph & Bo & Ho 3 44 13.5 3.27 <0.0001 Zo & Ph & Ch 3 48 16.3 2.95 <0.0001 Zo & Ph & Bo 3 41 12.5 3.27 <0.0001 Bo & Ca & Ho 3 89 42.3 2.10 <0.0001 Bo & Eq & Ca 3 28 6.3 4.47 <0.0001 Ph & Ch & Ps 3 52 19.6 2.65 <0.0001 Ch & Mo & Ca 3 99 51.1 1.94 <0.0001 Zo & Ps & Ho 3 72 32.3 2.23 <0.0001 Zo & Eq & Ho 3 22 4.2 5.18 <0.0001 Zo & Ph & Ps 3 27 6.4 4.22 <0.0001 Ch & Sa & Bo 3 67 30.4 2.20 <0.0001 Ph & Ps & Bo 3 43 15.2 2.84 <0.0001 Ps & Bo & Eq 3 35 11.3 3.09 <0.0001

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N genes N genes Intersections Degree FE P-value (shared) (expected)

Ch & Ps & Sa 3 42 15.5 2.70 <0.0001 Ch & Ca & Ho 3 100 54.9 1.82 <0.0001 Zo & Bo & Eq 3 31 9.4 3.31 <0.0001 Sa & Mo & Bo 3 32 9.9 3.22 <0.0001 Ps & Sa & Ho 3 23 5.4 4.23 <0.0001 Zo & Ch & Sa 3 36 12.8 2.80 <0.0001 Ps & Sa & Mo 3 21 5.1 4.15 <0.0001 Ph & Ch & Ho 3 43 17.5 2.46 <0.0001 Ps & Eq & Ho 3 21 5.1 4.09 <0.0001 Zo & Mo & Ca 3 42 16.6 2.52 <0.0001 Ch & Ps & Eq 3 38 14.7 2.59 <0.0001 Ps & Mo & Eq 3 20 4.8 4.18 <0.0001 Hi & Ch & Bo 3 55 26.2 2.10 <0.0001 Ch & Eq & Ca 3 26 8.1 3.20 <0.0001 Eq & Ca & Ho 3 15 2.8 5.28 <0.0001 Zo & Ps & Ca 3 46 20.1 2.29 <0.0001 Ch & Sa & Mo 3 34 12.9 2.64 <0.0001 Hi & Bo & Ca 3 21 5.7 3.68 <0.0001 Hi & Ch & Ho 3 31 11.9 2.61 <0.0001 Sa & Bo & Ho 3 29 10.7 2.72 <0.0001 Ph & Ch & Mo 3 38 16.3 2.34 <0.0001 Zo & Sa & Mo 3 17 4.2 4.06 <0.0001 Zo & Ph & Ho 3 20 5.7 3.52 <0.0001 Hi & Ps & Mo 3 17 4.3 3.91 <0.0001 Mo & Eq & Ca 3 13 2.6 4.91 <0.0001 Ph & Ps & Mo 3 20 6.4 3.12 <0.0001 Ph & Mo & Bo 3 30 12.6 2.39 <0.0001 Zo & Mo & Eq 3 15 4.0 3.79 <0.0001 Zo & Eq & Ca 3 12 2.6 4.54 <0.0001 Ps & Eq & Ca 3 13 3.2 4.07 <0.0001 Ph & Ps & Ho 3 20 6.9 2.91 <0.0001 Zo & Sa & Bo 3 25 9.9 2.52 <0.0001 Ps & Sa & Bo 3 28 12.0 2.34 <0.0001 Ph & Ps & Ca 3 15 4.3 3.50 <0.0001 Hi & Ps & Bo 3 25 10.3 2.43 <0.0001 Ch & Sa & Ho 3 30 13.8 2.17 <0.0001 Zo & Ph & Mo 3 16 5.3 3.02 0.0001 Ph & Bo & Ca 3 21 8.4 2.50 0.0001 Hi & Zo & Ch 3 25 11.0 2.27 0.0001 Hi & Mo & Ho 3 13 3.9 3.36 0.0002

39

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ca 3 10 2.4 4.16 0.0002 Ps & Ca & Ho 3 40 21.6 1.85 0.0002 Hi & Ch & Ps 3 28 13.3 2.10 0.0002 Ph & Bo & Eq 3 9 2.0 4.51 0.0002 Zo & Sa & Ho 3 14 4.5 3.11 0.0002 Sa & Mo & Ho 3 14 4.5 3.11 0.0002 Zo & Ps & Sa 3 15 5.1 2.97 0.0002 Ph & Ch & Ca 3 24 10.9 2.21 0.0003 Hi & Ch & Mo 3 24 11.0 2.17 0.0004 Hi & Ch & Eq 3 8 1.8 4.56 0.0004 Zo & Ca & Ho 3 33 17.9 1.85 0.0007 Ph & Mo & Ho 3 15 5.7 2.64 0.0007 Hi & Bo & Ho 3 20 9.2 2.19 0.001 Hi & Ca & Ho 3 9 2.6 3.48 0.001 Ps & Sa & Eq 3 5 0.8 6.22 0.001 Sa & Mo & Ca 3 9 2.8 3.21 0.002 Hi & Ph & Bo 3 7 1.8 3.86 0.003 Hi & Mo & Eq 3 4 0.6 6.99 0.003 Hi & Ps & Ca 3 9 2.9 3.10 0.003 Hi & Ps & Ho 3 12 4.7 2.57 0.003 Hi & Sa & Mo 3 4 0.6 6.60 0.003 Hi & Ch & Ca 3 16 7.4 2.17 0.003 Zo & Ps & Eq 3 12 4.8 2.51 0.004 Hi & Eq & Ho 3 4 0.6 6.51 0.004 Ph & Ps & Eq 3 5 1.0 4.91 0.004 Ch & Sa & Eq 3 7 2.0 3.43 0.005 Ph & Ps & Sa 3 5 1.1 4.64 0.005 Sa & Bo & Eq 3 6 1.6 3.80 0.005 Ph & Mo & Ca 3 9 3.5 2.54 0.010 Hi & Mo & Ca 3 7 2.4 2.91 0.011 Zo & Ph & Sa 3 4 0.9 4.49 0.013 Hi & Ph & Ca 3 3 0.5 5.85 0.015 Ph & Ca & Ho 3 9 3.8 2.36 0.016 Hi & Mo & Bo 3 15 8.5 1.76 0.026 Zo & Ph & Ca 3 8 3.5 2.26 0.028 Ch & Sa & Ca 3 15 8.6 1.74 0.028 Hi & Zo & Mo 3 8 3.6 2.22 0.030 Sa & Mo & Eq 3 3 0.7 4.50 0.030 Hi & Ph & Ch 3 6 2.4 2.55 0.032 Sa & Ca & Ho 3 7 3.0 2.33 0.033

40

N genes N genes Intersections Degree FE P-value (shared) (expected)

Sa & Bo & Ca 3 12 6.6 1.81 0.037 Hi & Ps & Sa 3 3 0.7 4.10 0.038 Hi & Ch & Sa 3 5 1.9 2.69 0.040 Hi & Bo & Eq 3 4 1.4 2.95 0.048 Zo & Ph & Eq 3 3 0.8 3.56 0.05 Ps & Sa & Ca 3 7 3.4 2.07 0.06 Ph & Ch & Sa 3 6 2.7 2.19 0.06 Ph & Sa & Bo 3 5 2.1 2.37 0.06 Zo & Sa & Ca 3 6 2.8 2.14 0.06 Hi & Zo & Bo 3 13 8.5 1.53 0.09 Hi & Sa & Eq 3 1 0.1 10.39 0.09 Ph & Eq & Ca 3 2 0.6 3.55 0.11 Ph & Sa & Ca 3 2 0.6 3.35 0.12 Hi & Zo & Sa 3 2 0.6 3.31 0.12 Hi & Sa & Ho 3 2 0.7 3.08 0.14 Zo & Sa & Eq 3 2 0.7 3.01 0.14 Hi & Ps & Eq 3 2 0.7 2.89 0.15 Sa & Eq & Ho 3 2 0.7 2.80 0.16 Hi & Ph & Ho 3 2 0.8 2.43 0.20 Ph & Sa & Mo 3 2 0.9 2.24 0.22 Ph & Eq & Ho 3 2 0.9 2.21 0.23 Hi & Ph & Ps 3 2 0.9 2.16 0.24 Ph & Sa & Ho 3 2 1.0 2.09 0.25 Ph & Ch & Eq 3 4 2.6 1.55 0.26 Hi & Zo & Ps 3 6 4.3 1.38 0.27 Hi & Eq & Ca 3 1 0.4 2.61 0.32 Hi & Sa & Ca 3 1 0.4 2.47 0.33 Hi & Zo & Ho 3 5 3.9 1.29 0.34 Hi & Sa & Bo 3 2 1.4 1.39 0.42 Hi & Zo & Eq 3 1 0.6 1.75 0.44 Hi & Zo & Ph 3 1 0.8 1.31 0.54 Hi & Ph & Mo 3 1 0.8 1.30 0.54 Ph & Mo & Eq 3 1 0.8 1.19 0.57 Sa & Eq & Ca 3 0 0.4 0.00 1 Ph & Sa & Eq 3 0 0.1 0.00 1 Hi & Ph & Sa 3 0 0.1 0.00 1 Hi & Ph & Eq 3 0 0.1 0.00 1 Ps & Mo & Bo & Ho 4 78 8.2 9.48 <0.0001 Ch & Ps & Bo & Ho 4 124 25.2 4.91 <0.0001 Ch & Ps & Mo & Ho 4 78 10.7 7.32 <0.0001

41

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ch & Mo & Bo & Ho 4 101 20.9 4.83 <0.0001 Ch & Ps & Mo & Bo 4 104 23.5 4.42 <0.0001 Zo & Ch & Ps & Bo 4 102 23.5 4.34 <0.0001 Zo & Ch & Bo & Ho 4 88 20.9 4.21 <0.0001 Ch & Ps & Bo & Ca 4 64 15.7 4.07 <0.0001 Zo & Ch & Mo & Bo 4 70 19.5 3.60 <0.0001 Ch & Bo & Eq & Ho 4 30 3.3 9.03 <0.0001 Ch & Mo & Bo & Eq 4 29 3.1 9.37 <0.0001 Zo & Ps & Mo & Ho 4 30 3.5 8.64 <0.0001 Zo & Ch & Ps & Mo 4 48 9.9 4.84 <0.0001 Zo & Ps & Mo & Bo 4 41 7.7 5.35 <0.0001 Zo & Mo & Bo & Ho 4 37 6.8 5.44 <0.0001 Zo & Ch & Ps & Ho 4 46 10.7 4.32 <0.0001 Zo & Ch & Bo & Ca 4 51 13.0 3.92 <0.0001 Zo & Ch & Eq & Ho 4 19 1.4 13.55 <0.0001 Ch & Mo & Eq & Ho 4 19 1.4 13.54 <0.0001 Ph & Ch & Ps & Bo 4 31 5.0 6.19 <0.0001 Ch & Ps & Mo & Ca 4 35 6.6 5.27 <0.0001 Ch & Bo & Ca & Ho 4 51 14.0 3.65 <0.0001 Zo & Ch & Mo & Ho 4 40 8.8 4.54 <0.0001 Zo & Ps & Bo & Ho 4 38 8.2 4.62 <0.0001 Mo & Bo & Eq & Ho 4 16 1.1 14.78 <0.0001 Ps & Mo & Bo & Ca 4 29 5.1 5.66 <0.0001 Zo & Ch & Ps & Ca 4 32 6.6 4.82 <0.0001 Ph & Ch & Bo & Ho 4 26 4.4 5.84 <0.0001 Zo & Ch & Bo & Eq 4 22 3.1 7.12 <0.0001 Ch & Ps & Sa & Mo 4 17 1.7 10.17 <0.0001 Mo & Bo & Ca & Ho 4 26 4.6 5.71 <0.0001 Ch & Sa & Mo & Bo 4 22 3.3 6.72 <0.0001 Ch & Mo & Bo & Ca 4 44 13.0 3.38 <0.0001 Ch & Ps & Mo & Eq 4 16 1.6 10.14 <0.0001 Zo & Ph & Ch & Bo 4 24 4.1 5.80 <0.0001 Ch & Ps & Bo & Eq 4 22 3.7 5.89 <0.0001 Ch & Ps & Sa & Ho 4 16 1.8 8.92 <0.0001 Zo & Ph & Ch & Ps 4 17 2.1 8.05 <0.0001 Ch & Ps & Sa & Bo 4 22 4.0 5.56 <0.0001 Ch & Ps & Eq & Ho 4 15 1.7 8.85 <0.0001 Ps & Mo & Bo & Eq 4 13 1.2 10.67 <0.0001 Ch & Sa & Bo & Ho 4 20 3.5 5.69 <0.0001 Mo & Eq & Ca & Ho 4 8 0.3 26.16 <0.0001

42

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ch & Sa & Bo 4 19 3.3 5.81 <0.0001 Ps & Mo & Ca & Ho 4 16 2.3 6.88 <0.0001 Ps & Mo & Eq & Ho 4 9 0.6 16.29 <0.0001 Ps & Sa & Mo & Ho 4 9 0.6 15.39 <0.0001 Zo & Ch & Mo & Eq 4 12 1.3 9.19 <0.0001 Ch & Mo & Ca & Ho 4 24 5.9 4.07 <0.0001 Zo & Bo & Eq & Ho 4 11 1.1 10.17 <0.0001 Zo & Ch & Ps & Sa 4 13 1.7 7.79 <0.0001 Zo & Ch & Sa & Mo 4 12 1.4 8.68 <0.0001 Zo & Mo & Eq & Ho 4 8 0.5 17.51 <0.0001 Ch & Bo & Eq & Ca 4 14 2.1 6.77 <0.0001 Ch & Eq & Ca & Ho 4 10 0.9 10.66 <0.0001 Ph & Ch & Mo & Bo 4 19 4.1 4.58 <0.0001 Zo & Ph & Ch & Ho 4 13 1.9 6.93 <0.0001 Zo & Ps & Sa & Mo 4 8 0.5 14.70 <0.0001 Ps & Sa & Mo & Bo 4 11 1.3 8.53 <0.0001 Ps & Sa & Bo & Ho 4 11 1.4 7.95 <0.0001 Ps & Bo & Ca & Ho 4 21 5.5 3.82 <0.0001 Ch & Mo & Eq & Ca 4 9 0.9 10.30 <0.0001 Zo & Mo & Bo & Ca 4 18 4.2 4.24 <0.0001 Mo & Bo & Eq & Ca 4 8 0.7 11.86 <0.0001 Ph & Ch & Ps & Ho 4 13 2.3 5.73 <0.0001 Bo & Eq & Ca & Ho 4 8 0.7 11.05 <0.0001 Zo & Ch & Ca & Ho 4 21 5.9 3.56 <0.0001 Zo & Mo & Bo & Eq 4 9 1.0 8.93 <0.0001 Zo & Ph & Ps & Bo 4 11 1.6 6.75 <0.0001 Ps & Bo & Eq & Ho 4 10 1.3 7.65 <0.0001 Zo & Ps & Bo & Ca 4 19 5.1 3.71 <0.0001 Zo & Sa & Mo & Bo 4 9 1.1 8.44 <0.0001 Ph & Ps & Bo & Ca 4 9 1.1 8.25 <0.0001 Ph & Ch & Ps & Mo 4 12 2.1 5.68 <0.0001 Ph & Ps & Bo & Ho 4 11 1.8 6.28 <0.0001 Hi & Ch & Bo & Ho 4 14 3.0 4.63 <0.0001 Zo & Sa & Bo & Ho 4 9 1.1 7.86 <0.0001 Ch & Sa & Mo & Ho 4 10 1.5 6.73 <0.0001 Zo & Ch & Eq & Ca 4 8 0.9 9.16 <0.0001 Hi & Ch & Bo & Ca 4 11 1.9 5.85 <0.0001 Zo & Mo & Ca & Ho 4 11 1.9 5.72 <0.0001 Hi & Ch & Ps & Bo 4 14 3.4 4.12 <0.0001 Ch & Ps & Eq & Ca 4 8 1.1 7.58 <0.0001

43

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ps & Mo & Ca 4 11 2.2 5.09 <0.0001 Ch & Ps & Ca & Ho 4 21 7.1 2.95 <0.0001 Zo & Ch & Mo & Ca 4 18 5.5 3.28 <0.0001 Zo & Eq & Ca & Ho 4 5 0.3 16.37 <0.0001 Zo & Ph & Bo & Ho 4 9 1.4 6.21 <0.0001 Ph & Mo & Bo & Ho 4 9 1.5 6.21 <0.0001 Zo & Bo & Ca & Ho 4 16 4.6 3.52 <0.0001 Ps & Bo & Eq & Ca 4 7 0.8 8.59 <0.0001 Zo & Ch & Sa & Ho 4 9 1.5 6.07 <0.0001 Sa & Mo & Bo & Ho 4 8 1.1 6.98 <0.0001 Ph & Ch & Mo & Ho 4 10 1.9 5.32 <0.0001 Hi & Ch & Ca & Ho 4 7 0.9 8.21 <0.0001 Hi & Ch & Ps & Ho 4 9 1.5 5.84 <0.0001 Zo & Ps & Sa & Ho 4 6 0.6 10.27 <0.0001 Hi & Zo & Bo & Ca 4 6 0.6 9.79 <0.0001 Hi & Mo & Eq & Ho 4 3 0.1 45.39 <0.0001 Ph & Ps & Mo & Bo 4 9 1.6 5.52 <0.0001 Hi & Ch & Mo & Ho 4 8 1.3 6.27 <0.0001 Ps & Sa & Bo & Eq 4 4 0.2 19.52 <0.0001 Sa & Mo & Bo & Ca 4 6 0.7 8.40 <0.0001 Ph & Ch & Ps & Ca 4 8 1.4 5.66 0.0001 Ph & Ps & Mo & Ho 4 6 0.7 8.11 0.0001 Hi & Ch & Ps & Mo 4 8 1.4 5.57 0.0001 Ph & Ch & Bo & Ca 4 11 2.8 3.97 0.0001 Zo & Sa & Mo & Ho 4 5 0.5 10.34 0.0001 Zo & Ps & Ca & Ho 4 10 2.3 4.31 0.0001 Ph & Ps & Ca & Ho 4 5 0.5 10.11 0.0002 Ch & Ps & Sa & Eq 4 4 0.3 15.06 0.0002 Ch & Sa & Bo & Eq 4 5 0.5 9.61 0.0002 Zo & Mo & Eq & Ca 4 4 0.3 14.05 0.0002 Zo & Ps & Eq & Ho 4 5 0.6 9.06 0.0003 Zo & Sa & Mo & Ca 4 4 0.3 13.28 0.0003 Hi & Ps & Mo & Ca 4 4 0.3 12.78 0.0003 Sa & Mo & Ca & Ho 4 4 0.3 12.36 0.0003 Zo & Ps & Sa & Bo 4 7 1.3 5.43 0.0004 Zo & Ph & Mo & Ho 4 5 0.6 8.17 0.0004 Hi & Mo & Bo & Ho 4 6 1.0 6.09 0.0005 Hi & Bo & Ca & Ho 4 5 0.7 7.59 0.0006 Zo & Bo & Eq & Ca 4 5 0.7 7.42 0.0006 Zo & Ph & Ps & Mo 4 5 0.7 7.26 0.0007

44

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ch & Mo & Eq 4 3 0.2 15.88 0.001 Zo & Ph & Ps & Ho 4 5 0.7 6.77 0.001 Zo & Ch & Ps & Eq 4 7 1.6 4.44 0.001 Hi & Ch & Eq & Ho 4 3 0.2 14.80 0.001 Hi & Zo & Ch & Ca 4 5 0.8 6.30 0.001 Hi & Ps & Bo & Ho 4 6 1.2 5.05 0.001 Ch & Sa & Mo & Eq 4 3 0.2 13.64 0.001 Hi & Ps & Mo & Ho 4 4 0.5 7.96 0.002 Zo & Ps & Mo & Eq 4 4 0.5 7.78 0.002 Hi & Zo & Ch & Bo 4 9 2.8 3.20 0.002 Hi & Ch & Mo & Bo 4 9 2.8 3.20 0.002 Ph & Ps & Bo & Eq 4 3 0.3 11.57 0.002 Ph & Ps & Eq & Ca 4 2 0.1 27.31 0.003 Zo & Ph & Mo & Bo 4 6 1.3 4.45 0.003 Hi & Ps & Mo & Eq 4 2 0.1 26.90 0.003 Ph & Ps & Sa & Bo 4 3 0.3 10.93 0.003 Hi & Ps & Sa & Mo 4 2 0.1 25.41 0.003 Hi & Ps & Eq & Ho 4 2 0.1 25.06 0.003 Ph & Bo & Ca & Ho 4 5 1.0 5.16 0.003 Ps & Sa & Mo & Eq 4 2 0.1 23.11 0.004 Hi & Mo & Bo & Ca 4 4 0.6 6.52 0.004 Zo & Ph & Sa & Mo 4 2 0.1 20.86 0.004 Hi & Ps & Mo & Bo 4 5 1.1 4.51 0.005 Ph & Ch & Sa & Bo 4 4 0.7 5.74 0.006 Ph & Ch & Ps & Sa 4 3 0.4 8.44 0.006 Zo & Ph & Ch & Ca 4 5 1.2 4.28 0.007 Ph & Ch & Mo & Ca 4 5 1.2 4.27 0.007 Hi & Ps & Bo & Ca 4 4 0.7 5.40 0.007 Hi & Zo & Ch & Mo 4 5 1.2 4.21 0.007 Ps & Sa & Ca & Ho 4 3 0.4 7.67 0.007 Sa & Bo & Ca & Ho 4 4 0.8 5.22 0.008 Zo & Ps & Bo & Eq 4 5 1.2 4.11 0.008 Zo & Ph & Ch & Mo 4 6 1.7 3.43 0.009 Ph & Bo & Eq & Ca 4 2 0.1 13.93 0.009 Hi & Mo & Bo & Eq 4 2 0.1 13.72 0.010 Hi & Zo & Sa & Eq 4 1 0.0 96.64 0.010 Hi & Ch & Bo & Eq 4 3 0.4 6.71 0.011 Hi & Bo & Eq & Ho 4 2 0.2 12.78 0.011 Ph & Ps & Mo & Ca 4 3 0.5 6.51 0.012 Hi & Zo & Ps & Mo 4 3 0.5 6.42 0.012

45

N genes N genes Intersections Degree FE P-value (shared) (expected)

Sa & Mo & Bo & Eq 4 2 0.2 11.79 0.013 Zo & Ph & Bo & Ca 4 4 0.9 4.43 0.013 Zo & Ch & Sa & Ca 4 4 0.9 4.33 0.014 Ch & Sa & Mo & Ca 4 4 0.9 4.32 0.015 Ph & Ch & Sa & Ca 4 2 0.2 10.16 0.017 Hi & Zo & Ch & Sa 4 2 0.2 10.01 0.017 Hi & Ch & Sa & Mo 4 2 0.2 10.00 0.017 Hi & Ch & Sa & Ho 4 2 0.2 9.32 0.020 Zo & Ch & Sa & Eq 4 2 0.2 9.10 0.021 Zo & Ph & Sa & Bo 4 2 0.2 8.81 0.022 Hi & Ch & Ps & Eq 4 2 0.2 8.77 0.022 Hi & Ph & Ch & Bo 4 3 0.6 5.01 0.023 Hi & Ph & Ps & Bo 4 2 0.2 8.48 0.024 Hi & Ch & Ps & Sa 4 2 0.2 8.28 0.025 Ph & Sa & Bo & Ho 4 2 0.2 8.20 0.025 Hi & Ph & Ch & Ho 4 2 0.3 7.37 0.031 Hi & Ch & Sa & Eq 4 1 0.0 31.47 0.031 Zo & Ph & Ch & Eq 4 2 0.3 7.20 0.032 Hi & Mo & Ca & Ho 4 2 0.3 7.19 0.032 Zo & Ph & Ch & Sa 4 2 0.3 6.80 0.036 Hi & Mo & Eq & Ca 4 1 0.0 24.29 0.040 Ph & Ch & Sa & Ho 4 2 0.3 6.33 0.040 Zo & Sa & Ca & Ho 4 2 0.3 6.18 0.042 Hi & Sa & Mo & Ca 4 1 0.0 22.95 0.043 Hi & Eq & Ca & Ho 4 1 0.0 22.63 0.043 Hi & Sa & Ca & Ho 4 1 0.0 21.38 0.046 Zo & Ps & Eq & Ca 4 2 0.3 5.82 0.047 Ps & Mo & Eq & Ca 4 2 0.3 5.81 0.047 Zo & Ps & Sa & Ca 4 2 0.4 5.50 0.05 Ps & Sa & Mo & Ca 4 2 0.4 5.49 0.05 Ps & Eq & Ca & Ho 4 2 0.4 5.42 0.05 Hi & Ph & Mo & Ca 4 1 0.1 18.14 0.05 Hi & Zo & Ch & Ps 4 4 1.4 2.79 0.06 Ph & Mo & Bo & Ca 4 3 0.9 3.32 0.06 Zo & Ph & Ca & Ho 4 2 0.4 4.89 0.06 Ph & Mo & Ca & Ho 4 2 0.4 4.88 0.06 Hi & Ph & Ps & Ca 4 1 0.1 15.02 0.06 Hi & Sa & Mo & Ho 4 1 0.1 14.29 0.07 Sa & Mo & Eq & Ho 4 1 0.1 13.00 0.07 Ph & Ps & Sa & Ca 4 1 0.1 12.90 0.07

46

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ph & Ps & Ca 4 2 0.5 4.34 0.08 Ch & Sa & Ca & Ho 4 3 1.0 3.02 0.08 Hi & Ps & Sa & Ho 4 1 0.1 11.84 0.08 Hi & Ch & Sa & Bo 4 2 0.5 4.23 0.08 Ps & Sa & Eq & Ho 4 1 0.1 10.76 0.09 Zo & Ph & Eq & Ho 4 1 0.1 10.28 0.09 Hi & Bo & Eq & Ca 4 1 0.1 10.26 0.09 Hi & Ph & Ps & Mo 4 1 0.1 10.04 0.09 Zo & Ph & Sa & Ho 4 1 0.1 9.72 0.10 Hi & Sa & Bo & Ca 4 1 0.1 9.69 0.10 Ch & Ps & Sa & Ca 4 3 1.1 2.69 0.10 Zo & Ph & Ps & Eq 4 1 0.1 9.14 0.10 Ph & Ps & Mo & Eq 4 1 0.1 9.13 0.10 Zo & Ph & Ps & Sa 4 1 0.1 8.64 0.11 Ph & Ps & Eq & Ho 4 1 0.1 8.51 0.11 Ph & Ps & Sa & Ho 4 1 0.1 8.04 0.12 Hi & Ph & Bo & Ca 4 1 0.1 7.66 0.12 Hi & Ch & Sa & Ca 4 1 0.1 7.48 0.13 Ph & Ch & Ca & Ho 4 3 1.3 2.39 0.13 Ph & Sa & Bo & Ca 4 1 0.2 6.58 0.14 Ph & Ch & Bo & Eq 4 2 0.7 3.04 0.14 Hi & Zo & Sa & Bo 4 1 0.2 6.49 0.14 Hi & Sa & Mo & Bo 4 1 0.2 6.48 0.14 Hi & Sa & Bo & Ho 4 1 0.2 6.04 0.15 Hi & Ph & Ch & Ca 4 1 0.2 5.91 0.16 Zo & Sa & Bo & Eq 4 1 0.2 5.90 0.16 Zo & Sa & Bo & Ca 4 2 0.7 2.80 0.16 Hi & Ps & Bo & Eq 4 1 0.2 5.68 0.16 Hi & Zo & Ch & Eq 4 1 0.2 5.30 0.17 Hi & Zo & Ph & Bo 4 1 0.2 5.13 0.18 Hi & Ph & Mo & Bo 4 1 0.2 5.12 0.18 Ch & Sa & Bo & Ca 4 4 2.2 1.83 0.18 Hi & Ph & Bo & Ho 4 1 0.2 4.77 0.19 Hi & Ch & Mo & Ca 4 2 0.8 2.52 0.19 Ph & Mo & Bo & Eq 4 1 0.2 4.66 0.19 Ch & Sa & Eq & Ho 4 1 0.2 4.24 0.21 Hi & Zo & Mo & Ca 4 1 0.3 3.86 0.23 Hi & Zo & Mo & Bo 4 2 0.9 2.18 0.23 Hi & Zo & Ca & Ho 4 1 0.3 3.60 0.24 Ph & Ch & Eq & Ho 4 1 0.3 3.35 0.26

47

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ph & Ch & Ps 4 1 0.3 3.27 0.26 Hi & Zo & Ps & Ca 4 1 0.3 3.20 0.27 Hi & Ps & Ca & Ho 4 1 0.3 2.98 0.29 Zo & Ph & Mo & Ca 4 1 0.4 2.62 0.32 Hi & Zo & Ch & Ho 4 2 1.3 1.57 0.36 Ps & Sa & Bo & Ca 4 1 0.9 1.16 0.58 Hi & Ch & Ps & Ca 4 1 1.0 1.04 0.62 Hi & Zo & Bo & Ho 4 1 1.0 1.02 0.63 Sa & Eq & Ca & Ho 4 0 0.1 0.00 1 Sa & Bo & Eq & Ho 4 0 0.2 0.00 1 Sa & Bo & Eq & Ca 4 0 0.1 0.00 1 Sa & Mo & Eq & Ca 4 0 0.0 0.00 1 Ps & Sa & Eq & Ca 4 0 0.1 0.00 1 Ch & Sa & Eq & Ca 4 0 0.1 0.00 1 Ph & Eq & Ca & Ho 4 0 0.1 0.00 1 Ph & Bo & Eq & Ho 4 0 0.2 0.00 1 Ph & Mo & Eq & Ho 4 0 0.1 0.00 1 Ph & Mo & Eq & Ca 4 0 0.1 0.00 1 Ph & Sa & Ca & Ho 4 0 0.1 0.00 1 Ph & Sa & Eq & Ho 4 0 0.0 0.00 1 Ph & Sa & Eq & Ca 4 0 0.0 0.00 1 Ph & Sa & Bo & Eq 4 0 0.0 0.00 1 Ph & Sa & Mo & Ho 4 0 0.1 0.00 1 Ph & Sa & Mo & Ca 4 0 0.1 0.00 1 Ph & Sa & Mo & Eq 4 0 0.0 0.00 1 Ph & Sa & Mo & Bo 4 0 0.2 0.00 1 Ph & Ps & Sa & Eq 4 0 0.0 0.00 1 Ph & Ps & Sa & Mo 4 0 0.1 0.00 1 Ph & Ch & Eq & Ca 4 0 0.2 0.00 1 Ph & Ch & Mo & Eq 4 0 0.3 0.00 1 Ph & Ch & Sa & Eq 4 0 0.0 0.00 1 Ph & Ch & Sa & Mo 4 0 0.3 0.00 1 Ph & Ch & Ps & Eq 4 0 0.3 0.00 1 Zo & Sa & Eq & Ho 4 0 0.1 0.00 1 Zo & Sa & Eq & Ca 4 0 0.0 0.00 1 Zo & Sa & Mo & Eq 4 0 0.1 0.00 1 Zo & Ps & Sa & Eq 4 0 0.1 0.00 1 Zo & Ph & Eq & Ca 4 0 0.1 0.00 1 Zo & Ph & Bo & Eq 4 0 0.2 0.00 1 Zo & Ph & Mo & Eq 4 0 0.1 0.00 1

48

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ph & Sa & Ca 4 0 0.1 0.00 1 Zo & Ph & Sa & Eq 4 0 0.0 0.00 1 Hi & Ph & Ps & Sa 4 0 0.0 0.00 1 Hi & Ph & Ch & Sa 4 0 0.0 0.00 1 Hi & Zo & Ps & Sa 4 0 0.1 0.00 1 Hi & Zo & Ph & Sa 4 0 0.0 0.00 1 Hi & Zo & Ph & Ps 4 0 0.1 0.00 1 Hi & Zo & Ph & Ch 4 0 0.3 0.00 1 Hi & Sa & Eq & Ho 4 0 0.0 0.00 1 Hi & Sa & Eq & Ca 4 0 0.0 0.00 1 Hi & Sa & Bo & Eq 4 0 0.0 0.00 1 Hi & Sa & Mo & Eq 4 0 0.0 0.00 1 Hi & Ps & Eq & Ca 4 0 0.0 0.00 1 Hi & Ps & Sa & Ca 4 0 0.1 0.00 1 Hi & Ps & Sa & Eq 4 0 0.0 0.00 1 Hi & Ps & Sa & Bo 4 0 0.2 0.00 1 Hi & Ch & Eq & Ca 4 0 0.1 0.00 1 Hi & Ph & Ca & Ho 4 0 0.1 0.00 1 Hi & Ph & Eq & Ho 4 0 0.0 0.00 1 Hi & Ph & Eq & Ca 4 0 0.0 0.00 1 Hi & Ph & Bo & Eq 4 0 0.0 0.00 1 Hi & Ph & Mo & Ho 4 0 0.1 0.00 1 Hi & Ph & Mo & Eq 4 0 0.0 0.00 1 Hi & Ph & Sa & Ho 4 0 0.0 0.00 1 Hi & Ph & Sa & Ca 4 0 0.0 0.00 1 Hi & Ph & Sa & Eq 4 0 0.0 0.00 1 Hi & Ph & Sa & Bo 4 0 0.0 0.00 1 Hi & Ph & Sa & Mo 4 0 0.0 0.00 1 Hi & Ph & Ps & Ho 4 0 0.1 0.00 1 Hi & Ph & Ps & Eq 4 0 0.0 0.00 1 Hi & Ph & Ch & Eq 4 0 0.0 0.00 1 Hi & Ph & Ch & Mo 4 0 0.3 0.00 1 Hi & Zo & Eq & Ho 4 0 0.1 0.00 1 Hi & Zo & Eq & Ca 4 0 0.0 0.00 1 Hi & Zo & Bo & Eq 4 0 0.1 0.00 1 Hi & Zo & Mo & Ho 4 0 0.4 0.00 1 Hi & Zo & Mo & Eq 4 0 0.1 0.00 1 Hi & Zo & Sa & Ho 4 0 0.1 0.00 1 Hi & Zo & Sa & Ca 4 0 0.0 0.00 1 Hi & Zo & Sa & Mo 4 0 0.1 0.00 1

49

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ps & Ho 4 0 0.5 0.00 1 Hi & Zo & Ps & Eq 4 0 0.1 0.00 1 Hi & Zo & Ps & Bo 4 0 1.1 0.00 1 Hi & Zo & Ph & Ho 4 0 0.1 0.00 1 Hi & Zo & Ph & Ca 4 0 0.1 0.00 1 Hi & Zo & Ph & Eq 4 0 0.0 0.00 1 Hi & Zo & Ph & Mo 4 0 0.1 0.00 1 Ch & Ps & Mo & Bo & Ho 5 45 2.7 16.57 <0.0001 Zo & Ch & Ps & Mo & Ho 5 19 1.1 16.58 <0.0001 Zo & Ps & Mo & Bo & Ho 5 17 0.9 19.22 <0.0001 Zo & Ch & Ps & Bo & Ho 5 25 2.7 9.21 <0.0001 Zo & Ch & Mo & Bo & Ho 5 22 2.2 9.79 <0.0001 Zo & Ch & Ps & Mo & Bo 5 23 2.5 9.10 <0.0001 Ch & Mo & Bo & Eq & Ho 5 12 0.4 33.57 <0.0001 Zo & Ch & Mo & Eq & Ho 5 8 0.2 53.04 <0.0001 Ch & Ps & Mo & Bo & Eq 5 10 0.4 24.87 <0.0001 Zo & Ch & Ps & Sa & Mo 5 8 0.2 44.54 <0.0001 Ch & Ps & Mo & Eq & Ho 5 8 0.2 43.88 <0.0001 Ch & Ps & Mo & Bo & Ca 5 16 1.7 9.46 <0.0001 Zo & Ch & Bo & Eq & Ho 5 9 0.4 25.20 <0.0001 Ch & Mo & Bo & Ca & Ho 5 14 1.5 9.31 <0.0001 Ch & Ps & Bo & Eq & Ho 5 9 0.4 20.85 <0.0001 Ch & Ps & Sa & Bo & Ho 5 9 0.5 19.70 <0.0001 Ch & Ps & Sa & Mo & Ho 5 7 0.2 36.27 <0.0001 Zo & Ch & Ps & Bo & Ca 5 14 1.7 8.28 <0.0001 Zo & Ph & Ch & Ps & Bo 5 9 0.5 16.73 <0.0001 Ch & Ps & Sa & Mo & Bo 5 8 0.4 18.79 <0.0001 Mo & Bo & Eq & Ca & Ho 5 5 0.1 64.18 <0.0001 Zo & Ph & Ch & Bo & Ho 5 8 0.5 16.73 <0.0001 Zo & Ch & Mo & Bo & Eq 5 7 0.3 21.04 <0.0001 Zo & Ch & Bo & Ca & Ho 5 12 1.5 7.99 <0.0001 Ch & Ps & Bo & Ca & Ho 5 13 1.8 7.16 <0.0001 Zo & Ch & Eq & Ca & Ho 5 5 0.1 49.58 <0.0001 Ch & Mo & Eq & Ca & Ho 5 5 0.1 49.53 <0.0001 Zo & Ch & Sa & Mo & Bo 5 7 0.4 19.88 <0.0001 Ch & Ps & Mo & Ca & Ho 5 9 0.8 11.73 <0.0001 Ch & Mo & Bo & Eq & Ca 5 6 0.2 26.95 <0.0001 Zo & Ch & Sa & Bo & Ho 5 7 0.4 18.52 <0.0001 Ps & Mo & Bo & Ca & Ho 5 8 0.6 13.51 <0.0001 Zo & Ch & Ps & Sa & Bo 5 7 0.4 16.46 <0.0001

50

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ps & Sa & Mo & Bo & Ho 5 5 0.1 33.57 <0.0001 Zo & Ps & Sa & Mo & Ho 5 4 0.1 63.65 <0.0001 Ph & Ch & Mo & Bo & Ho 5 7 0.5 14.62 <0.0001 Zo & Ch & Ps & Mo & Ca 5 8 0.7 11.20 <0.0001 Zo & Ch & Ps & Sa & Ho 5 5 0.2 25.93 <0.0001 Ph & Ch & Ps & Bo & Ho 5 7 0.6 12.11 <0.0001 Ch & Bo & Eq & Ca & Ho 5 5 0.2 20.92 <0.0001 Zo & Mo & Eq & Ca & Ho 5 3 0.0 91.26 <0.0001 Zo & Ph & Ch & Ps & Ho 5 5 0.2 20.50 <0.0001 Ph & Ch & Ps & Mo & Ho 5 5 0.2 20.48 <0.0001 Zo & Ps & Mo & Ca & Ho 5 5 0.2 20.01 <0.0001 Zo & Mo & Bo & Eq & Ho 5 4 0.1 34.37 <0.0001 Zo & Mo & Bo & Ca & Ho 5 6 0.5 12.25 <0.0001 Zo & Ps & Sa & Mo & Bo 5 4 0.1 28.86 <0.0001 Ps & Mo & Bo & Eq & Ho 5 4 0.1 28.43 <0.0001 Ph & Ch & Ps & Mo & Bo 5 6 0.5 11.14 <0.0001 Hi & Ch & Mo & Bo & Ho 5 5 0.3 15.38 <0.0001 Zo & Ch & Sa & Mo & Ho 5 4 0.2 25.06 <0.0001 Zo & Ps & Mo & Eq & Ho 5 3 0.1 50.53 <0.0001 Hi & Ps & Mo & Eq & Ho 5 2 0.0 232.86 <0.0001 Zo & Ch & Ps & Eq & Ho 5 4 0.2 21.96 <0.0001 Ph & Ps & Mo & Bo & Ho 5 4 0.2 21.23 <0.0001 Ch & Sa & Mo & Bo & Ho 5 5 0.4 13.22 <0.0001 Ch & Ps & Sa & Bo & Eq 5 3 0.1 44.35 <0.0001 Zo & Ch & Mo & Ca & Ho 5 6 0.6 9.45 <0.0001 Hi & Zo & Ch & Bo & Ca 5 4 0.2 19.77 <0.0001 Hi & Ch & Bo & Ca & Ho 5 4 0.2 18.40 <0.0001 Zo & Ch & Bo & Eq & Ca 5 4 0.2 17.98 <0.0001 Sa & Mo & Bo & Ca & Ho 5 3 0.1 36.38 <0.0001 Zo & Ch & Mo & Bo & Ca 5 8 1.4 5.72 0.0001 Zo & Ch & Mo & Eq & Ca 5 3 0.1 31.93 0.0001 Hi & Mo & Bo & Eq & Ho 5 2 0.0 118.79 0.0001 Zo & Ch & Sa & Mo & Ca 5 3 0.1 30.17 0.0002 Ph & Ps & Bo & Eq & Ca 5 2 0.0 107.21 0.0002 Ch & Ps & Bo & Eq & Ca 5 4 0.3 14.88 0.0002 Hi & Ch & Mo & Eq & Ho 5 2 0.0 91.67 0.0002 Zo & Ps & Mo & Bo & Ca 5 5 0.6 9.07 0.0003 Hi & Ch & Ps & Mo & Eq 5 2 0.0 81.48 0.0003 Ph & Ps & Bo & Ca & Ho 5 3 0.1 23.81 0.0003 Hi & Ch & Ps & Eq & Ho 5 2 0.0 75.90 0.0003

51

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ps & Bo & Ca & Ho 5 5 0.6 8.45 0.0004 Ch & Ps & Sa & Mo & Eq 5 2 0.0 70.00 0.0004 Zo & Ps & Sa & Bo & Ho 5 3 0.1 20.16 0.0005 Ph & Ch & Ps & Bo & Ca 5 4 0.4 11.11 0.0005 Ph & Ch & Ps & Ca & Ho 5 3 0.2 18.37 0.0006 Hi & Ch & Ps & Mo & Ho 5 3 0.2 18.09 0.0007 Zo & Ch & Ps & Mo & Eq 5 3 0.2 17.68 0.0007 Hi & Ch & Ps & Bo & Ho 5 4 0.4 10.19 0.0007 Zo & Ps & Sa & Ca & Ho 5 2 0.0 47.59 0.0009 Ps & Sa & Mo & Ca & Ho 5 2 0.0 47.55 0.0009 Zo & Ph & Ch & Mo & Bo 5 4 0.4 8.98 0.001 Zo & Ch & Ps & Ca & Ho 5 5 0.8 6.52 0.001 Zo & Ph & Ch & Mo & Ho 5 3 0.2 14.85 0.001 Ch & Sa & Mo & Bo & Eq 5 2 0.1 35.71 0.002 Zo & Ph & Ch & Ps & Mo 5 3 0.2 13.20 0.002 Hi & Mo & Bo & Ca & Ho 5 2 0.1 28.23 0.002 Zo & Mo & Bo & Eq & Ca 5 2 0.1 27.58 0.002 Zo & Ph & Ch & Sa & Bo 5 2 0.1 26.69 0.003 Zo & Sa & Mo & Bo & Ca 5 2 0.1 26.06 0.003 Zo & Bo & Eq & Ca & Ho 5 2 0.1 25.70 0.003 Zo & Ph & Ps & Mo & Ho 5 2 0.1 25.15 0.003 Ph & Ch & Sa & Bo & Ho 5 2 0.1 24.84 0.003 Hi & Zo & Ch & Sa & Eq 5 1 0.0 292.76 0.003 Zo & Ph & Ch & Bo & Ca 5 3 0.3 10.07 0.004 Ps & Mo & Bo & Eq & Ca 5 2 0.1 22.82 0.004 Ph & Ch & Ps & Sa & Bo 5 2 0.1 22.08 0.004 Ps & Bo & Eq & Ca & Ho 5 2 0.1 21.26 0.004 Hi & Mo & Eq & Ca & Ho 5 1 0.0 210.29 0.005 Hi & Sa & Mo & Ca & Ho 5 1 0.0 198.67 0.005 Ch & Sa & Mo & Ca & Ho 5 2 0.1 18.72 0.005 Zo & Ch & Ps & Eq & Ca 5 2 0.1 17.63 0.006 Ch & Ps & Mo & Eq & Ca 5 2 0.1 17.61 0.006 Hi & Ch & Ps & Mo & Bo 5 3 0.4 8.20 0.006 Ch & Ps & Eq & Ca & Ho 5 2 0.1 16.40 0.007 Zo & Sa & Mo & Bo & Ho 5 2 0.1 16.23 0.007 Hi & Ph & Ps & Mo & Ca 5 1 0.0 139.57 0.007 Hi & Ps & Mo & Bo & Ho 5 2 0.1 15.63 0.007 Zo & Ps & Mo & Bo & Eq 5 2 0.1 15.27 0.008 Zo & Ch & Ps & Bo & Eq 5 3 0.4 7.47 0.008 Zo & Ps & Bo & Eq & Ho 5 2 0.1 14.23 0.009

52

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ps & Sa & Mo & Eq & Ho 5 1 0.0 100.03 0.010 Zo & Ph & Ch & Ps & Ca 5 2 0.2 13.16 0.010 Ph & Ch & Ps & Mo & Ca 5 2 0.2 13.15 0.010 Hi & Mo & Bo & Eq & Ca 5 1 0.0 95.34 0.010 Hi & Zo & Ch & Ps & Mo 5 2 0.2 12.96 0.011 Zo & Ph & Mo & Bo & Ho 5 2 0.2 12.83 0.011 Hi & Sa & Mo & Bo & Ca 5 1 0.0 90.07 0.011 Hi & Bo & Eq & Ca & Ho 5 1 0.0 88.82 0.011 Hi & Sa & Bo & Ca & Ho 5 1 0.0 83.91 0.012 Zo & Ph & Ps & Mo & Bo 5 2 0.2 11.40 0.014 Hi & Ph & Mo & Bo & Ca 5 1 0.0 71.19 0.014 Hi & Ch & Sa & Mo & Ca 5 1 0.0 69.51 0.014 Hi & Ch & Sa & Ca & Ho 5 1 0.0 64.76 0.015 Zo & Ph & Ps & Bo & Ho 5 2 0.2 10.62 0.016 Hi & Ph & Ps & Bo & Ca 5 1 0.0 58.95 0.017 Hi & Sa & Mo & Bo & Ho 5 1 0.0 56.11 0.018 Hi & Ch & Mo & Bo & Ca 5 2 0.2 9.88 0.018 Hi & Ps & Mo & Bo & Eq 5 1 0.0 52.79 0.019 Hi & Ps & Bo & Eq & Ho 5 1 0.0 49.18 0.020 Ps & Sa & Mo & Bo & Eq 5 1 0.0 45.35 0.022 Hi & Ch & Sa & Mo & Ho 5 1 0.0 43.30 0.023 Ch & Sa & Mo & Bo & Ca 5 2 0.2 8.49 0.024 Hi & Ph & Ps & Mo & Bo 5 1 0.0 39.42 0.025 Ch & Sa & Mo & Eq & Ho 5 1 0.0 39.38 0.025 Ph & Ch & Ps & Sa & Ca 5 1 0.0 39.08 0.025 Hi & Ch & Ps & Sa & Mo 5 1 0.0 38.49 0.026 Zo & Ph & Sa & Bo & Ho 5 1 0.0 38.14 0.026 Hi & Ch & Ps & Sa & Ho 5 1 0.0 35.86 0.028 Ph & Ps & Mo & Bo & Eq 5 1 0.0 35.85 0.028 Zo & Ph & Ps & Sa & Bo 5 1 0.0 33.90 0.029 Ch & Ps & Sa & Eq & Ho 5 1 0.0 32.61 0.030 Ph & Ps & Sa & Bo & Ho 5 1 0.0 31.55 0.031 Zo & Ph & Ch & Eq & Ho 5 1 0.0 31.15 0.032 Hi & Zo & Ps & Mo & Ca 5 1 0.0 29.73 0.033 Zo & Ph & Ch & Sa & Ho 5 1 0.0 29.43 0.033 Hi & Ch & Sa & Bo & Ca 5 1 0.0 29.36 0.033 Zo & Sa & Mo & Ca & Ho 5 1 0.0 28.74 0.034 Zo & Ps & Mo & Eq & Ca 5 1 0.0 27.04 0.036 Ph & Ch & Mo & Bo & Ca 5 2 0.3 6.71 0.036 Zo & Ph & Ch & Ps & Sa 5 1 0.0 26.16 0.038

53

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ps & Sa & Mo & Ca 5 1 0.0 25.54 0.038 Zo & Ps & Eq & Ca & Ho 5 1 0.0 25.19 0.039 Ps & Mo & Eq & Ca & Ho 5 1 0.0 25.16 0.039 Ph & Ch & Ps & Sa & Ho 5 1 0.0 24.35 0.040 Zo & Ph & Mo & Ca & Ho 5 1 0.0 22.71 0.043 Hi & Ch & Mo & Bo & Eq 5 1 0.0 20.78 0.047 Ph & Ch & Sa & Bo & Ca 5 1 0.1 19.94 0.049 Hi & Zo & Ch & Sa & Bo 5 1 0.1 19.65 0.050 Hi & Ch & Sa & Mo & Bo 5 1 0.1 19.63 0.050 Hi & Ch & Bo & Eq & Ho 5 1 0.1 19.36 0.05 Zo & Ph & Ps & Ca & Ho 5 1 0.1 18.81 0.05 Ph & Ps & Mo & Ca & Ho 5 1 0.1 18.79 0.05 Hi & Ch & Sa & Bo & Ho 5 1 0.1 18.29 0.05 Zo & Ch & Sa & Bo & Eq 5 1 0.1 17.87 0.05 Hi & Ch & Ps & Bo & Eq 5 1 0.1 17.21 0.06 Hi & Ph & Ch & Bo & Ho 5 1 0.1 14.46 0.07 Hi & Zo & Bo & Ca & Ho 5 1 0.1 14.13 0.07 Hi & Ph & Ch & Ps & Bo 5 1 0.1 12.85 0.07 Hi & Ps & Mo & Bo & Ca 5 1 0.1 12.55 0.08 Zo & Ps & Bo & Eq & Ca 5 1 0.1 11.42 0.08 Hi & Zo & Ch & Ca & Ho 5 1 0.1 10.90 0.09 Hi & Ch & Mo & Ca & Ho 5 1 0.1 10.89 0.09 Ps & Sa & Mo & Bo & Ca 5 1 0.1 10.78 0.09 Ps & Sa & Bo & Ca & Ho 5 1 0.1 10.04 0.09 Zo & Ch & Sa & Ca & Ho 5 1 0.1 9.37 0.10 Hi & Ch & Ps & Ca & Ho 5 1 0.1 9.02 0.10 Zo & Ph & Ps & Bo & Ca 5 1 0.1 8.53 0.11 Ph & Ps & Mo & Bo & Ca 5 1 0.1 8.52 0.11 Zo & Ch & Ps & Sa & Ca 5 1 0.1 8.33 0.11 Ch & Ps & Sa & Mo & Ca 5 1 0.1 8.32 0.11 Ch & Ps & Sa & Ca & Ho 5 1 0.1 7.75 0.12 Zo & Ph & Ch & Ca & Ho 5 1 0.1 7.40 0.13 Ph & Ch & Mo & Ca & Ho 5 1 0.1 7.40 0.13 Zo & Ch & Sa & Bo & Ca 5 1 0.2 4.25 0.21 Ch & Sa & Bo & Ca & Ho 5 1 0.3 3.95 0.22 Hi & Zo & Ch & Mo & Bo 5 1 0.3 3.31 0.26 Ph & Ch & Bo & Ca & Ho 5 1 0.3 3.12 0.27 Hi & Zo & Ch & Bo & Ho 5 1 0.3 3.08 0.28 Sa & Bo & Eq & Ca & Ho 5 0 0.0 0.00 1 Sa & Mo & Eq & Ca & Ho 5 0 0.0 0.00 1

54

N genes N genes Intersections Degree FE P-value (shared) (expected)

Sa & Mo & Bo & Eq & Ho 5 0 0.0 0.00 1 Sa & Mo & Bo & Eq & Ca 5 0 0.0 0.00 1 Ps & Sa & Eq & Ca & Ho 5 0 0.0 0.00 1 Ps & Sa & Bo & Eq & Ho 5 0 0.0 0.00 1 Ps & Sa & Bo & Eq & Ca 5 0 0.0 0.00 1 Ps & Sa & Mo & Eq & Ca 5 0 0.0 0.00 1 Ch & Sa & Eq & Ca & Ho 5 0 0.0 0.00 1 Ch & Sa & Bo & Eq & Ho 5 0 0.1 0.00 1 Ch & Sa & Bo & Eq & Ca 5 0 0.0 0.00 1 Ch & Sa & Mo & Eq & Ca 5 0 0.0 0.00 1 Ch & Ps & Sa & Eq & Ca 5 0 0.0 0.00 1 Ch & Ps & Sa & Bo & Ca 5 0 0.3 0.00 1 Ph & Bo & Eq & Ca & Ho 5 0 0.0 0.00 1 Ph & Mo & Eq & Ca & Ho 5 0 0.0 0.00 1 Ph & Mo & Bo & Ca & Ho 5 0 0.1 0.00 1 Ph & Mo & Bo & Eq & Ho 5 0 0.0 0.00 1 Ph & Mo & Bo & Eq & Ca 5 0 0.0 0.00 1 Ph & Sa & Eq & Ca & Ho 5 0 0.0 0.00 1 Ph & Sa & Bo & Ca & Ho 5 0 0.0 0.00 1 Ph & Sa & Bo & Eq & Ho 5 0 0.0 0.00 1 Ph & Sa & Bo & Eq & Ca 5 0 0.0 0.00 1 Ph & Sa & Mo & Ca & Ho 5 0 0.0 0.00 1 Ph & Sa & Mo & Eq & Ho 5 0 0.0 0.00 1 Ph & Sa & Mo & Eq & Ca 5 0 0.0 0.00 1 Ph & Sa & Mo & Bo & Ho 5 0 0.0 0.00 1 Ph & Sa & Mo & Bo & Ca 5 0 0.0 0.00 1 Ph & Sa & Mo & Bo & Eq 5 0 0.0 0.00 1 Ph & Ps & Eq & Ca & Ho 5 0 0.0 0.00 1 Ph & Ps & Bo & Eq & Ho 5 0 0.0 0.00 1 Ph & Ps & Mo & Eq & Ho 5 0 0.0 0.00 1 Ph & Ps & Mo & Eq & Ca 5 0 0.0 0.00 1 Ph & Ps & Sa & Ca & Ho 5 0 0.0 0.00 1 Ph & Ps & Sa & Eq & Ho 5 0 0.0 0.00 1 Ph & Ps & Sa & Eq & Ca 5 0 0.0 0.00 1 Ph & Ps & Sa & Bo & Ca 5 0 0.0 0.00 1 Ph & Ps & Sa & Bo & Eq 5 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Ho 5 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Ca 5 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Eq 5 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo 5 0 0.0 0.00 1

55

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ph & Ch & Eq & Ca & Ho 5 0 0.0 0.00 1 Ph & Ch & Bo & Eq & Ho 5 0 0.1 0.00 1 Ph & Ch & Bo & Eq & Ca 5 0 0.0 0.00 1 Ph & Ch & Mo & Eq & Ho 5 0 0.0 0.00 1 Ph & Ch & Mo & Eq & Ca 5 0 0.0 0.00 1 Ph & Ch & Mo & Bo & Eq 5 0 0.1 0.00 1 Ph & Ch & Sa & Ca & Ho 5 0 0.0 0.00 1 Ph & Ch & Sa & Eq & Ho 5 0 0.0 0.00 1 Ph & Ch & Sa & Eq & Ca 5 0 0.0 0.00 1 Ph & Ch & Sa & Bo & Eq 5 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Ho 5 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Ca 5 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Eq 5 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo 5 0 0.1 0.00 1 Ph & Ch & Ps & Eq & Ho 5 0 0.0 0.00 1 Ph & Ch & Ps & Eq & Ca 5 0 0.0 0.00 1 Ph & Ch & Ps & Bo & Eq 5 0 0.1 0.00 1 Ph & Ch & Ps & Mo & Eq 5 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Eq 5 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo 5 0 0.0 0.00 1 Zo & Sa & Eq & Ca & Ho 5 0 0.0 0.00 1 Zo & Sa & Bo & Ca & Ho 5 0 0.1 0.00 1 Zo & Sa & Bo & Eq & Ho 5 0 0.0 0.00 1 Zo & Sa & Bo & Eq & Ca 5 0 0.0 0.00 1 Zo & Sa & Mo & Eq & Ho 5 0 0.0 0.00 1 Zo & Sa & Mo & Eq & Ca 5 0 0.0 0.00 1 Zo & Sa & Mo & Bo & Eq 5 0 0.0 0.00 1 Zo & Ps & Sa & Eq & Ho 5 0 0.0 0.00 1 Zo & Ps & Sa & Eq & Ca 5 0 0.0 0.00 1 Zo & Ps & Sa & Bo & Ca 5 0 0.1 0.00 1 Zo & Ps & Sa & Bo & Eq 5 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Eq 5 0 0.0 0.00 1 Zo & Ch & Sa & Eq & Ho 5 0 0.0 0.00 1 Zo & Ch & Sa & Eq & Ca 5 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Eq 5 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Eq 5 0 0.0 0.00 1 Zo & Ph & Eq & Ca & Ho 5 0 0.0 0.00 1 Zo & Ph & Bo & Ca & Ho 5 0 0.1 0.00 1 Zo & Ph & Bo & Eq & Ho 5 0 0.0 0.00 1 Zo & Ph & Bo & Eq & Ca 5 0 0.0 0.00 1

56

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ph & Mo & Eq & Ho 5 0 0.0 0.00 1 Zo & Ph & Mo & Eq & Ca 5 0 0.0 0.00 1 Zo & Ph & Mo & Bo & Ca 5 0 0.1 0.00 1 Zo & Ph & Mo & Bo & Eq 5 0 0.0 0.00 1 Zo & Ph & Sa & Ca & Ho 5 0 0.0 0.00 1 Zo & Ph & Sa & Eq & Ho 5 0 0.0 0.00 1 Zo & Ph & Sa & Eq & Ca 5 0 0.0 0.00 1 Zo & Ph & Sa & Bo & Ca 5 0 0.0 0.00 1 Zo & Ph & Sa & Bo & Eq 5 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Ho 5 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Ca 5 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Eq 5 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo 5 0 0.0 0.00 1 Zo & Ph & Ps & Eq & Ho 5 0 0.0 0.00 1 Zo & Ph & Ps & Eq & Ca 5 0 0.0 0.00 1 Zo & Ph & Ps & Bo & Eq 5 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Ca 5 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Eq 5 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Ho 5 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Ca 5 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Eq 5 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo 5 0 0.0 0.00 1 Zo & Ph & Ch & Eq & Ca 5 0 0.0 0.00 1 Zo & Ph & Ch & Bo & Eq 5 0 0.1 0.00 1 Zo & Ph & Ch & Mo & Ca 5 0 0.1 0.00 1 Zo & Ph & Ch & Mo & Eq 5 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Ca 5 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Eq 5 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo 5 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Eq 5 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa 5 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa 5 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa 5 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa 5 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps 5 0 0.0 0.00 1 Hi & Sa & Eq & Ca & Ho 5 0 0.0 0.00 1 Hi & Sa & Bo & Eq & Ho 5 0 0.0 0.00 1 Hi & Sa & Bo & Eq & Ca 5 0 0.0 0.00 1 Hi & Sa & Mo & Eq & Ho 5 0 0.0 0.00 1 Hi & Sa & Mo & Eq & Ca 5 0 0.0 0.00 1

57

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Sa & Mo & Bo & Eq 5 0 0.0 0.00 1 Hi & Ps & Eq & Ca & Ho 5 0 0.0 0.00 1 Hi & Ps & Bo & Ca & Ho 5 0 0.1 0.00 1 Hi & Ps & Bo & Eq & Ca 5 0 0.0 0.00 1 Hi & Ps & Mo & Ca & Ho 5 0 0.0 0.00 1 Hi & Ps & Mo & Eq & Ca 5 0 0.0 0.00 1 Hi & Ps & Sa & Ca & Ho 5 0 0.0 0.00 1 Hi & Ps & Sa & Eq & Ho 5 0 0.0 0.00 1 Hi & Ps & Sa & Eq & Ca 5 0 0.0 0.00 1 Hi & Ps & Sa & Bo & Ho 5 0 0.0 0.00 1 Hi & Ps & Sa & Bo & Ca 5 0 0.0 0.00 1 Hi & Ps & Sa & Bo & Eq 5 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Ho 5 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Ca 5 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Eq 5 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo 5 0 0.0 0.00 1 Hi & Ch & Eq & Ca & Ho 5 0 0.0 0.00 1 Hi & Ch & Bo & Eq & Ca 5 0 0.0 0.00 1 Hi & Ch & Mo & Eq & Ca 5 0 0.0 0.00 1 Hi & Ch & Sa & Eq & Ho 5 0 0.0 0.00 1 Hi & Ch & Sa & Eq & Ca 5 0 0.0 0.00 1 Hi & Ch & Sa & Bo & Eq 5 0 0.0 0.00 1 Hi & Ch & Sa & Mo & Eq 5 0 0.0 0.00 1 Hi & Ch & Ps & Eq & Ca 5 0 0.0 0.00 1 Hi & Ch & Ps & Bo & Ca 5 0 0.2 0.00 1 Hi & Ch & Ps & Mo & Ca 5 0 0.1 0.00 1 Hi & Ch & Ps & Sa & Ca 5 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Eq 5 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Bo 5 0 0.1 0.00 1 Hi & Ph & Eq & Ca & Ho 5 0 0.0 0.00 1 Hi & Ph & Bo & Ca & Ho 5 0 0.0 0.00 1 Hi & Ph & Bo & Eq & Ho 5 0 0.0 0.00 1 Hi & Ph & Bo & Eq & Ca 5 0 0.0 0.00 1 Hi & Ph & Mo & Ca & Ho 5 0 0.0 0.00 1 Hi & Ph & Mo & Eq & Ho 5 0 0.0 0.00 1 Hi & Ph & Mo & Eq & Ca 5 0 0.0 0.00 1 Hi & Ph & Mo & Bo & Ho 5 0 0.0 0.00 1 Hi & Ph & Mo & Bo & Eq 5 0 0.0 0.00 1 Hi & Ph & Sa & Ca & Ho 5 0 0.0 0.00 1 Hi & Ph & Sa & Eq & Ho 5 0 0.0 0.00 1

58

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ph & Sa & Eq & Ca 5 0 0.0 0.00 1 Hi & Ph & Sa & Bo & Ho 5 0 0.0 0.00 1 Hi & Ph & Sa & Bo & Ca 5 0 0.0 0.00 1 Hi & Ph & Sa & Bo & Eq 5 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Ho 5 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Ca 5 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Eq 5 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo 5 0 0.0 0.00 1 Hi & Ph & Ps & Ca & Ho 5 0 0.0 0.00 1 Hi & Ph & Ps & Eq & Ho 5 0 0.0 0.00 1 Hi & Ph & Ps & Eq & Ca 5 0 0.0 0.00 1 Hi & Ph & Ps & Bo & Ho 5 0 0.0 0.00 1 Hi & Ph & Ps & Bo & Eq 5 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Ho 5 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Eq 5 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Ho 5 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Ca 5 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Eq 5 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo 5 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo 5 0 0.0 0.00 1 Hi & Ph & Ch & Ca & Ho 5 0 0.0 0.00 1 Hi & Ph & Ch & Eq & Ho 5 0 0.0 0.00 1 Hi & Ph & Ch & Eq & Ca 5 0 0.0 0.00 1 Hi & Ph & Ch & Bo & Ca 5 0 0.0 0.00 1 Hi & Ph & Ch & Bo & Eq 5 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Ho 5 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Ca 5 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Eq 5 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo 5 0 0.1 0.00 1 Hi & Ph & Ch & Sa & Ho 5 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Ca 5 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Eq 5 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo 5 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo 5 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Ho 5 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Ca 5 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Eq 5 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo 5 0 0.0 0.00 1 Hi & Zo & Eq & Ca & Ho 5 0 0.0 0.00 1 Hi & Zo & Bo & Eq & Ho 5 0 0.0 0.00 1

59

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Bo & Eq & Ca 5 0 0.0 0.00 1 Hi & Zo & Mo & Ca & Ho 5 0 0.0 0.00 1 Hi & Zo & Mo & Eq & Ho 5 0 0.0 0.00 1 Hi & Zo & Mo & Eq & Ca 5 0 0.0 0.00 1 Hi & Zo & Mo & Bo & Ho 5 0 0.1 0.00 1 Hi & Zo & Mo & Bo & Ca 5 0 0.1 0.00 1 Hi & Zo & Mo & Bo & Eq 5 0 0.0 0.00 1 Hi & Zo & Sa & Ca & Ho 5 0 0.0 0.00 1 Hi & Zo & Sa & Eq & Ho 5 0 0.0 0.00 1 Hi & Zo & Sa & Eq & Ca 5 0 0.0 0.00 1 Hi & Zo & Sa & Bo & Ho 5 0 0.0 0.00 1 Hi & Zo & Sa & Bo & Ca 5 0 0.0 0.00 1 Hi & Zo & Sa & Bo & Eq 5 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Ho 5 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Ca 5 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Eq 5 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo 5 0 0.0 0.00 1 Hi & Zo & Ps & Ca & Ho 5 0 0.0 0.00 1 Hi & Zo & Ps & Eq & Ho 5 0 0.0 0.00 1 Hi & Zo & Ps & Eq & Ca 5 0 0.0 0.00 1 Hi & Zo & Ps & Bo & Ho 5 0 0.1 0.00 1 Hi & Zo & Ps & Bo & Ca 5 0 0.1 0.00 1 Hi & Zo & Ps & Bo & Eq 5 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Ho 5 0 0.1 0.00 1 Hi & Zo & Ps & Mo & Eq 5 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Bo 5 0 0.1 0.00 1 Hi & Zo & Ps & Sa & Ho 5 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Ca 5 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Eq 5 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo 5 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo 5 0 0.0 0.00 1 Hi & Zo & Ch & Eq & Ho 5 0 0.0 0.00 1 Hi & Zo & Ch & Eq & Ca 5 0 0.0 0.00 1 Hi & Zo & Ch & Bo & Eq 5 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Ho 5 0 0.1 0.00 1 Hi & Zo & Ch & Mo & Ca 5 0 0.1 0.00 1 Hi & Zo & Ch & Mo & Eq 5 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Ho 5 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Ca 5 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo 5 0 0.0 0.00 1

60

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ch & Ps & Ho 5 0 0.2 0.00 1 Hi & Zo & Ch & Ps & Ca 5 0 0.1 0.00 1 Hi & Zo & Ch & Ps & Eq 5 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo 5 0 0.4 0.00 1 Hi & Zo & Ph & Ca & Ho 5 0 0.0 0.00 1 Hi & Zo & Ph & Eq & Ho 5 0 0.0 0.00 1 Hi & Zo & Ph & Eq & Ca 5 0 0.0 0.00 1 Hi & Zo & Ph & Bo & Ho 5 0 0.0 0.00 1 Hi & Zo & Ph & Bo & Ca 5 0 0.0 0.00 1 Hi & Zo & Ph & Bo & Eq 5 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Ho 5 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Ca 5 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Eq 5 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo 5 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Ho 5 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Ca 5 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Eq 5 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Bo 5 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo 5 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Ho 5 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Ca 5 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Eq 5 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo 5 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo 5 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ho 5 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ca 5 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Eq 5 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Bo 5 0 0.1 0.00 1 Hi & Zo & Ph & Ch & Mo 5 0 0.0 0.00 1 Zo & Ch & Ps & Mo & Bo & Ho 6 11 0.3 37.67 <0.0001 Zo & Ch & Ps & Sa & Mo & Ho 6 4 0.0 192.81 <0.0001 Ch & Ps & Mo & Bo & Ca & Ho 6 6 0.2 30.70 <0.0001 Zo & Ch & Mo & Bo & Eq & Ho 6 4 0.0 104.10 <0.0001 Zo & Ch & Ps & Sa & Mo & Bo 6 4 0.0 87.42 <0.0001 Ch & Ps & Mo & Bo & Eq & Ho 6 4 0.0 86.12 <0.0001 Zo & Ch & Mo & Eq & Ca & Ho 6 3 0.0 276.45 <0.0001 Zo & Ch & Ps & Mo & Eq & Ho 6 3 0.0 153.06 <0.0001 Ch & Mo & Bo & Eq & Ca & Ho 6 3 0.0 116.66 <0.0001 Hi & Ch & Ps & Mo & Eq & Ho 6 2 0.0 705.44 <0.0001 Zo & Ch & Ps & Sa & Bo & Ho 6 3 0.0 61.08 <0.0001

61

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ch & Ps & Sa & Mo & Bo & Ho 6 3 0.0 61.02 <0.0001 Zo & Ch & Mo & Bo & Ca & Ho 6 4 0.2 24.74 <0.0001 Zo & Mo & Bo & Eq & Ca & Ho 6 2 0.0 238.81 <0.0001 Ph & Ch & Ps & Mo & Bo & Ho 6 3 0.1 48.23 <0.0001 Zo & Ch & Ps & Mo & Bo & Ca 6 4 0.2 21.99 <0.0001 Zo & Ps & Mo & Bo & Ca & Ho 6 3 0.1 47.14 <0.0001 Zo & Ch & Ps & Mo & Ca & Ho 6 3 0.1 36.38 <0.0001 Zo & Ps & Sa & Mo & Bo & Ho 6 2 0.0 124.92 0.0001 Zo & Ch & Mo & Bo & Eq & Ca 6 2 0.0 83.56 0.0003 Zo & Ch & Bo & Eq & Ca & Ho 6 2 0.0 77.84 0.0003 Zo & Ph & Ch & Ps & Mo & Ho 6 2 0.0 76.20 0.0003 Ch & Ps & Mo & Bo & Eq & Ca 6 2 0.0 69.12 0.0004 Ch & Ps & Bo & Eq & Ca & Ho 6 2 0.0 64.40 0.0005 Zo & Ch & Sa & Mo & Bo & Ho 6 2 0.0 49.18 0.0008 Hi & Ch & Ps & Mo & Bo & Ho 6 2 0.0 47.35 0.0009 Zo & Ch & Ps & Bo & Eq & Ho 6 2 0.0 43.10 0.001 Zo & Ch & Ps & Bo & Ca & Ho 6 3 0.2 15.37 0.001 Hi & Mo & Bo & Eq & Ca & Ho 6 1 0.0 825.48 0.001 Zo & Ph & Ch & Mo & Bo & Ho 6 2 0.1 38.87 0.001 Hi & Sa & Mo & Bo & Ca & Ho 6 1 0.0 779.87 0.001 Zo & Ph & Ch & Ps & Mo & Bo 6 2 0.1 34.55 0.002 Hi & Ch & Sa & Mo & Ca & Ho 6 1 0.0 601.85 0.002 Hi & Ph & Ps & Mo & Bo & Ca 6 1 0.0 547.86 0.002 Zo & Ph & Ch & Ps & Bo & Ho 6 2 0.1 32.18 0.002 Hi & Ps & Mo & Bo & Eq & Ho 6 1 0.0 457.04 0.002 Ch & Ps & Sa & Mo & Eq & Ho 6 1 0.0 303.03 0.003 Hi & Ch & Sa & Mo & Bo & Ca 6 1 0.0 272.87 0.004 Hi & Ch & Sa & Bo & Ca & Ho 6 1 0.0 254.21 0.004 Zo & Ps & Mo & Eq & Ca & Ho 6 1 0.0 234.08 0.004 Zo & Ps & Sa & Mo & Ca & Ho 6 1 0.0 221.15 0.005 Hi & Ch & Mo & Bo & Eq & Ho 6 1 0.0 179.92 0.006 Hi & Ch & Sa & Mo & Bo & Ho 6 1 0.0 169.98 0.006 Hi & Ch & Ps & Mo & Bo & Eq 6 1 0.0 159.92 0.006 Hi & Ch & Ps & Bo & Eq & Ho 6 1 0.0 148.98 0.007 Ch & Ps & Sa & Mo & Bo & Eq 6 1 0.0 137.39 0.007 Zo & Ph & Ch & Sa & Bo & Ho 6 1 0.0 115.53 0.009 Zo & Ps & Mo & Bo & Eq & Ca 6 1 0.0 106.13 0.009 Zo & Ph & Ch & Ps & Sa & Bo 6 1 0.0 102.69 0.010 Zo & Ps & Bo & Eq & Ca & Ho 6 1 0.0 98.87 0.010 Ps & Mo & Bo & Eq & Ca & Ho 6 1 0.0 98.78 0.010

62

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ph & Ch & Ps & Sa & Bo & Ho 6 1 0.0 95.57 0.010 Ps & Sa & Mo & Bo & Ca & Ho 6 1 0.0 93.32 0.011 Zo & Ch & Sa & Mo & Ca & Ho 6 1 0.0 87.06 0.011 Zo & Ch & Ps & Mo & Eq & Ca 6 1 0.0 81.90 0.012 Zo & Ch & Ps & Sa & Mo & Ca 6 1 0.0 77.38 0.013 Zo & Ch & Ps & Eq & Ca & Ho 6 1 0.0 76.30 0.013 Ch & Ps & Mo & Eq & Ca & Ho 6 1 0.0 76.23 0.013 Zo & Ch & Ps & Sa & Ca & Ho 6 1 0.0 72.09 0.014 Ch & Ps & Sa & Mo & Ca & Ho 6 1 0.0 72.02 0.014 Zo & Ps & Mo & Bo & Eq & Ho 6 1 0.0 66.11 0.015 Zo & Ph & Ch & Ps & Ca & Ho 6 1 0.0 56.98 0.017 Ph & Ch & Ps & Mo & Ca & Ho 6 1 0.0 56.92 0.017 Zo & Ph & Ps & Mo & Bo & Ho 6 1 0.0 49.37 0.020 Hi & Zo & Ch & Bo & Ca & Ho 6 1 0.0 42.80 0.023 Hi & Ch & Mo & Bo & Ca & Ho 6 1 0.0 42.76 0.023 Zo & Ch & Sa & Mo & Bo & Ca 6 1 0.0 39.47 0.025 Ch & Sa & Mo & Bo & Ca & Ho 6 1 0.0 36.74 0.027 Zo & Ch & Ps & Bo & Eq & Ca 6 1 0.0 34.59 0.028 Zo & Ph & Ch & Ps & Bo & Ca 6 1 0.0 25.83 0.038 Ph & Ch & Ps & Bo & Ca & Ho 6 1 0.0 24.04 0.041 Zo & Ch & Ps & Mo & Bo & Eq 6 1 0.0 23.13 0.042 Sa & Mo & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ps & Sa & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ps & Sa & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ps & Sa & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Ps & Sa & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Ch & Sa & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ch & Sa & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ch & Sa & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Ch & Sa & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Ch & Ps & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Ch & Ps & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Ch & Ps & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Ch & Ps & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Ch & Ps & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Ch & Ps & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Ph & Mo & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Sa & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Sa & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Sa & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1

63

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ph & Sa & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Ph & Sa & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ps & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Ps & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Ps & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1 Ph & Ps & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ps & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ps & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Ps & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Ph & Ps & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ps & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Ca & Ho 6 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo & Ho 6 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Ph & Ch & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Ch & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Ch & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1 Ph & Ch & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ch & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ch & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Ch & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Ph & Ch & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ch & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Ca & Ho 6 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo & Ho 6 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Ph & Ch & Ps & Eq & Ca & Ho 6 0 0.0 0.00 1 Ph & Ch & Ps & Bo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ch & Ps & Bo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Eq & Ho 6 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Eq & Ca 6 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Bo & Ca 6 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Bo & Eq 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Ca & Ho 6 0 0.0 0.00 1

64

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ph & Ch & Ps & Sa & Eq & Ho 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Eq & Ca 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Bo & Ca 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Bo & Eq 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Ho 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Ca 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Eq 6 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo 6 0 0.0 0.00 1 Zo & Sa & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Sa & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Sa & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1 Zo & Sa & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Zo & Sa & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ps & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Ps & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ps & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ps & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Zo & Ch & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Ch & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ch & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ch & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Eq & Ho 6 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Eq & Ca 6 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Bo & Ca 6 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Bo & Eq 6 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Eq 6 0 0.0 0.00 1 Zo & Ph & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1

65

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ph & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo & Ho 6 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ps & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Bo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Bo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Bo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Bo & Ca 6 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Bo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Bo & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Bo & Ca 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Bo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Ho 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Ca 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo 6 0 0.0 0.00 1 Zo & Ph & Ch & Eq & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Bo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Bo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Bo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Bo & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Bo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Ca & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Bo & Ca 6 0 0.0 0.00 1

66

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ph & Ch & Sa & Bo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Eq & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Eq & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Bo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Eq 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Ho 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Ca 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Eq 6 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa 6 0 0.0 0.00 1 Hi & Sa & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Sa & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Sa & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Sa & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ps & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ps & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ps & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ps & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ps & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ps & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ps & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ps & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Ch & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ch & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ch & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ch & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ch & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ch & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ch & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1

67

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ch & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ch & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Ch & Ps & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ch & Ps & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ch & Ps & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ch & Ps & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ch & Ps & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ch & Ps & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Ca & Ho 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Eq & Ho 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Eq & Ca 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Bo & Ho 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Bo & Ca 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Bo & Eq 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Ho 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Ca 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Eq 6 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo 6 0 0.0 0.00 1 Hi & Ph & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ps & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Eq & Ca 6 0 0.0 0.00 1

68

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ph & Ps & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo & Ca 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Ca 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo 6 0 0.0 0.00 1 Hi & Ph & Ch & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Ca & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Eq & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Eq & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Bo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Bo & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Bo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Ca 6 0 0.0 0.00 1

69

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ph & Ch & Ps & Mo & Eq 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Ho 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Ca 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Eq 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo 6 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo 6 0 0.0 0.00 1 Hi & Zo & Bo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Mo & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Mo & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Mo & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Mo & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Sa & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Sa & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Sa & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Sa & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ps & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Ca 6 0 0.0 0.00 1

70

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ps & Sa & Mo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo 6 0 0.0 0.00 1 Hi & Zo & Ch & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Bo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Bo 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Ho 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Ca 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Eq 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo 6 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo 6 0 0.0 0.00 1 Hi & Zo & Ph & Eq & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Bo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Bo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Bo & Eq & Ca 6 0 0.0 0.00 1

71

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ph & Mo & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ca & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Eq & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Eq & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Bo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Bo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Bo & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Eq 6 0 0.0 0.00 1

72

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ph & Ch & Mo & Bo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Ho 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Ca 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Eq 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo 6 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo 6 0 0.0 0.00 1 Zo & Ch & Mo & Bo & Eq & Ca & Ho 7 2 0.0 723.45 <0.0001 Zo & Ch & Ps & Sa & Mo & Bo & Ho 7 2 0.0 378.43 <0.0001 Zo & Ch & Ps & Mo & Bo & Ca & Ho 7 2 0.0 95.20 0.0002 Hi & Ch & Sa & Mo & Bo & Ca & Ho 7 1 0.0 2362.52 0.0004 Hi & Ch & Ps & Mo & Bo & Eq & Ho 7 1 0.0 1384.56 0.0007 Zo & Ps & Mo & Bo & Eq & Ca & Ho 7 1 0.0 918.86 0.001 Zo & Ch & Ps & Mo & Eq & Ca & Ho 7 1 0.0 709.12 0.001 Zo & Ch & Ps & Sa & Mo & Ca & Ho 7 1 0.0 669.94 0.001 Zo & Ch & Ps & Mo & Bo & Eq & Ca 7 1 0.0 321.50 0.003 Zo & Ch & Ps & Bo & Eq & Ca & Ho 7 1 0.0 299.51 0.003 Ch & Ps & Mo & Bo & Eq & Ca & Ho 7 1 0.0 299.24 0.003 Zo & Ch & Ps & Mo & Bo & Eq & Ho 7 1 0.0 200.28 0.005 Zo & Ph & Ch & Ps & Mo & Bo & Ho 7 1 0.0 149.55 0.007 Ps & Sa & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ch & Sa & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ch & Ps & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ch & Ps & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ch & Ps & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Ch & Ps & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Ch & Ps & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1

73

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ph & Sa & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ps & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ps & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Ph & Ch & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Ph & Ch & Ps & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo & 7 0 0.0 0.00 1

74

N genes N genes Intersections Degree FE P-value (shared) (expected)

Eq Zo & Sa & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ps & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ch & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1 Zo & Ph & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ps & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1

75

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ph & Ps & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1 Zo & Ph & Ch & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo & 7 0 0.0 0.00 1

76

N genes N genes Intersections Degree FE P-value (shared) (expected)

Eq Zo & Ph & Ch & Ps & Eq & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Bo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Bo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Bo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Bo & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Bo & Eq 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Ca & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Eq & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Eq & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Bo & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Bo & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Bo & Eq 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Ho 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Ca 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Eq 7 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo 7 0 0.0 0.00 1 Hi & Sa & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ps & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ps & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ch & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1

77

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ch & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ch & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ch & Ps & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Ph & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ps & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Bo & Eq & 7 0 0.0 0.00 1

78

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ho Hi & Ph & Ps & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Ph & Ch & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Eq & Ca & Ho 7 0 0.0 0.00 1

79

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ph & Ch & Ps & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Ca & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Eq & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Eq & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo & Eq 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Ho 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Ca 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Eq 7 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo 7 0 0.0 0.00 1 Hi & Zo & Mo & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Sa & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ps & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Bo & Ca & 7 0 0.0 0.00 1

80

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ho Hi & Zo & Ps & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ch & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1

81

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ch & Ps & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo 7 0 0.0 0.00 1 Hi & Zo & Ph & Bo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Bo & Eq & 7 0 0.0 0.00 1

82

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ho Hi & Zo & Ph & Sa & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo 7 0 0.0 0.00 1

83

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ph & Ch & Eq & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Bo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Bo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Bo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Ca & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Eq & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Eq & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & 7 0 0.0 0.00 1

84

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ca Hi & Zo & Ph & Ch & Ps & Mo & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Ho 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Ca 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Eq 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Bo 7 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo 7 0 0.0 0.00 1 Zo & Ch & Ps & Mo & Bo & Eq & Ca & Ho 8 1 0.0 2783.58 0.0004 Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Ph & Ps & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Ph & Ch & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Ph & Ch & Ps & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Zo & Ps & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ch & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Zo & Ph & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ps & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1

85

N genes N genes Intersections Degree FE P-value (shared) (expected)

Zo & Ph & Ps & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Zo & Ph & Ch & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Eq & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Bo & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Bo & Eq & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Bo & Eq & Ca 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Ca & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Eq & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Eq & Ca 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo & Ho 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo & Ca 8 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq 8 0 0.0 0.00 1 Hi & Ps & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ch & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ch & Ps & Mo & Bo & Eq & 8 0 0.0 0.00 1

86

N genes N genes Intersections Degree FE P-value (shared) (expected)

Ca & Ho Hi & Ch & Ps & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Ph & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ps & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Ph & Ch & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo & Eq & Ca 8 0 0.0 0.00 1

87

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Ph & Ch & Ps & Sa & Mo & Ca & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Eq & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Eq & Ca 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo & Ho 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo & Ca 8 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo & Eq 8 0 0.0 0.00 1 Hi & Zo & Sa & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ps & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ch & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo & 8 0 0.0 0.00 1

88

N genes N genes Intersections Degree FE P-value (shared) (expected)

Eq & Ca Hi & Zo & Ch & Ps & Sa & Mo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo & Ho 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo & Ca 8 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo & Eq 8 0 0.0 0.00 1 Hi & Zo & Ph & Mo & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo & Eq 8 0 0.0 0.00 1

89

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ph & Ch & Bo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo & Eq 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Eq & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Eq & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo & Eq 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Ca & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Eq & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & 8 0 0.0 0.00 1

90

N genes N genes Intersections Degree FE P-value (shared) (expected)

Eq & Ca Hi & Zo & Ph & Ch & Ps & Sa & Bo & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Bo & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Bo & Eq 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Ho 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Ca 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Eq 8 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo 8 0 0.0 0.00 1 Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Zo & Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Zo & Ph & Ps & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Zo & Ph & Ch & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Eq & Ca & Ho 9 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo & Ca & Ho 9 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ho 9 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca 9 0 0.0 0.00 1 Hi & Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Ph & Ps & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Ph & Ch & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo & Ca & Ho 9 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ho 9 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca 9 0 0.0 0.00 1 Hi & Zo & Ps & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1

91

N genes N genes Intersections Degree FE P-value (shared) (expected)

Hi & Zo & Ch & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo & Eq & Ho 9 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo & Eq & Ca 9 0 0.0 0.00 1 Hi & Zo & Ph & Sa & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo & Eq & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo & Eq & Ca 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Mo & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo & Eq & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo & Eq & Ca 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Bo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo & Eq & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo & Eq & Ca 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Eq & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Bo & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & 9 0 0.0 0.00 1

92

N genes N genes Intersections Degree FE P-value (shared) (expected)

Bo & Eq & Ho Hi & Zo & Ph & Ch & Ps & Sa & Bo & Eq & Ca 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Ca & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Eq & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Eq & Ca 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo & Ho 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo & Ca 9 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq 9 0 0.0 0.00 1 Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ps & Sa & Mo & Bo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Sa & Mo & Bo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Mo & Bo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Bo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Eq & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo & Ca & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ho 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca 10 0 0.0 0.00 1 Hi & Zo & Ph & Ch & Ps & Sa & Mo & Bo & Eq & Ca & Ho 11 0 0.0 0.00 1 466 467 468

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469 Supplementary Table 20. Overlap of genes that were differentially expressed by at least four viviparous vertebrates and identified as candidate 470 genes in admixture mapping of parity mode in common lizards. 471 sum sum gene Sum mapped adjusted MM GS mammals squamates chr position module symbol shared all phenotype p-value score score shared shared ASAH1 2 4 6 retention 0.00016 8 32886588 NA NA NA PLP1 3 3 6 retention 0.00519 8 69068927 NA NA NA SLC22A23 3 3 6 retention 0.00604 10 42133960 NA NA NA EPAS1 3 3 6 retention 0.00864 5 17270575 NA NA NA ATP8A1 1 4 5 retention 0 8 33759119 NA NA NA ITPK1 1 4 5 retention_eggshell 0.00012 3 20417670 NA NA NA LYN 2 3 5 retention_eggshell 0 7 43181374 NA NA NA ADIPOR2 2 3 5 retention 0.00298 14 53619964 NA NA NA LGMN 3 2 5 retention_eggshell 0.00012 3 20417670 NA NA NA FRMPD4 3 2 5 retention 0.00519 8 69068927 NA NA NA CREG1 2 2 5 retention 0.00639 13 37829883 NA NA NA FGL1 5 0 5 retention 0.00016 8 32886588 NA NA NA PCM1 1 3 4 retention 0.00016 8 32886588 NA NA NA LINGO1 1 3 4 retention 0.00035 8 60068071 NA NA NA SSR3 1 3 4 retention 0.00082 19 29171686 NA NA NA FHL3 1 3 4 retention 0.00397 2 41781143 NA NA NA HSD17B2 1 3 4 retention 0.00864 2 61858188 NA NA NA BBX 2 2 4 retention 0 13 33948401 NA NA NA LYPLA1 2 2 4 retention_eggshell 0 7 43181374 NA NA NA LRRK1 2 2 4 retention 0.00012 11 33283843 NA NA NA ALDH1A3 2 2 4 retention 0.00012 11 33283843 NA NA NA C3 2 2 4 retention 0.00015 16 33009028 NA NA NA EIF5A2 2 2 4 retention 0.00016 10 45186089 NA NA NA DOK4 2 2 4 retention 0.00048 2 42614456 NA NA NA KANK3 2 2 4 retention 0.00067 1 106349594 darkgreen 0.832 0.856 FURIN 2 2 4 retention 0.00129 11 29579573 NA NA NA LPCAT2 2 2 4 retention 0.00864 2 61858188 NA NA NA LONRF2 1 2 4 retention 0 8 97513078 NA NA NA

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PDIA3 1 2 4 retention 0.00129 11 29579573 NA NA NA ESM1 1 2 4 retention 0.00945 17 21047056 NA NA NA TMEM47 3 1 4 retention 0 8 83716265 NA NA NA SLC2A1 3 1 4 retention 0.00016 10 45186089 NA NA NA SLC7A2 3 1 4 retention 0.00016 8 32886588 NA NA NA PLLP 3 1 4 retention 0.00048 2 42614456 NA NA NA NCAPG 3 1 4 retention 0.00056 8 36076269 NA NA NA LCP2 3 1 4 eggshell 0.00202 1 44772143 NA NA NA HTRA3 3 1 4 retention 0.00431 8 61054269 NA NA NA CD47 3 1 4 retention 0.00824 13 34274703 NA NA NA

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472 Supplementary Table 21. List of viviparous species with data on differentially expressed 473 genes in reproductive tissue between pregnant and non-pregnant states. Species are ordered 474 by class. References from which data were extracted are indicated in the last column. 475 N diff. Species Order Class Reference genes Hippocampus abdominalis Syngnathiformes Actinopterygii 311 37 Bos taurus Artiodactyla Mammalia 195 38 Capra aegagrus Artiodactyla Mammalia 3231 39 Sus scrofa Artiodactyla Mammalia 2223 40 Canis lupus Carnivora Mammalia 1439 41 Monodelphis domestica Didelphimorphia Mammalia 2152 42 Equus caballus Perissodactyla Mammalia 342 43 Homo sapiens Primates Mammalia 2310 44 Chalcides ocellatus Squmata Reptilia 6602 45 Phrynocepahlus vlangalii Squmata Reptilia 458 34 Pseudemoia entrecasteauxii Squmata Reptilia 2599 46 Saiphos equalis Squmata Reptilia 362 33 Zootoca vivipara Squmata Reptilia 2150 this study 476

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