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Epimutations in Developmental Genes Underlie the Onset of Domestication in Farmed European Sea Bass

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Epimutations in Developmental Genes Underlie the Onset of Domestication in Farmed European Sea Bass SUPPLEMENTARY MATERIAL ONLINE Epimutations in developmental genes underlie the onset of domestication in farmed European sea bass Dafni Anastasiadi, Francesc Piferrer* Institute of Marine Sciences, Spanish National Research Council (CSIC) Passeig Marítim , 37 -49, 08003, Barcelona, Spain *Correspondence to: [email protected] 1 Supplementary Figures Supplementary figure 1. Examples of the domestication syndrome in fish. a) Overall morpholo gical differences between wild (W) and farmed (F) European sea bass (Dicentrarchus labrax ) in Greece (GR) and Spain (SP) as assessed by principal component analysis. Figure redrawn from Arechavala -López et al. (2012) . b) Lower jaw deformity in farmed Europ ean sea bass. Top fish: normal jaw; bottom fish: prognathism . Photo by Dr. Dafni Anastasiadi. c) Skin depigmentation in turbot ( Scophthalmus maximus ). Photo courtesy of Dr. Josep Rotllant. d) Number of differentially expressed genes in the brain, liver and muscle of domesticated vs. wild rainbow trout ( Oncorhynchus mykiss ) reared under the same environment. Figure redrawn from Tymchuk et al. (2009) . e) Gonadosomatic index of wild and captive -reared greater amberjack ( Seriola dumerili ) individuals at the sta ges of advanced gametogenesis. Figure redrawn from Zupa et al. (2017) . f) Number of aggression acts per 10 minutes of wild and farmed Atlantic salmon ( Salmo salar ) individuals. Figure redrawn from (Huntingford 2004) , in turn based on Fleming et al. (1996) . Supplementary figure 2. Genes under positive selection in the European sea bass after 25 years of selective breeding and in mammalian and avian domesticates. The genes with signatures of selection in the sea bass were identified in a previous, unrelated study (Bertolini et al. 2016) . They represent the consensus of genes under selection in two independent sea bass hatcheries towards the same direction. The gene s localized in the virtual chromosome “UN”, which contains 96,939,502 bp out of the total 675,917,103 bp of the sea bass genome (Tine et al. 2014 ) were excluded from the analysis. The presence of similar genes in other species was based on previous published studies in dog (Pendleton et al. 2018) , cat (Montague et al. 2014) , horse (Schubert et al. 2014) , rabbit (Carneiro et al. 2014) , fox (Kukekova et al. 2018) and duck (Zhang et al. 2018) . The top 10 genes are shown as ranked according to the number of species (shown in the last column) in which they are under positive selection. Genes related to the neural crest were identified based on two published studies (Martinez -Morales et al. 2007; Dooley et al. 2019) and are shaded in grey. The numbers under the species symbol represent the total number of annotated genes under positive selection. Supplementary figure 3. Experimental design, showing wild and early domesticate sea bass used in this study, sampling and analysis. Supplementary figure 4. Robustness of the DNA methylation data obtained by RRBS in a total of 24 samples from four tissues o f adult European sea bass. Pairwise comparisons of values (0 to 1 in the X and Y axes) in a) brain, b) muscle, c) testis and d) liver between wild (w) and early domesticate (f) fish. DNA methylation is shown as pairwise scatterplots in the lower left part of each figure and as histograms for each sample on the diagonal. In the upper right part of each figure, pairwise Pearson’s correlation scores are indicated. The mean Pearson’s correlation scores for brain, muscle, testis and liver were 0.93, 0.89, 0.96 a nd 0.94, respectively. Each sample represents an independent replicate. Supplementary figure 5. Distribution of differentially methylated regions (DMRs) in genes and genomic features. a) Numbers of DMRs inside first exons (orange), first introns (light blue), rest of exons (purple), rest of introns (mustard), 5 kb upstream the transcription start site (dark blue), 5 kb downstream the transcription termination site (dark purple) and in intergenic regions (red). b) Numbers of DMRs inside CpG islands (must ard), CpG shores ± 2 kb around the islands (blue) and outside CpG islands and shores (red). c) Percentage of genes with hypo - (green) and hyper -methylated (red) DMRs inside the gene bodies or ± 5000 bp flanking regions. n=3 independent replicates per group and per tissue. Supplementary figure 6. Validation of DNA methylation results (DNA me) obtained by reduced representation bisulfite sequencing (RRBS) with multiplex bisulfite sequencing (MBS). Each datapoint corresponds to an individual CpG pertaini ng to one of the following genes: gria4a and phld in brain, mapk8a and adamsts9 in muscle, foxc1 in testis, and pcdh γ - a11 -like in liver. Pearson’s correlation (rho) and significance ( p) values are indicated. Percentage data are shown as means of n = 6 (RR BS) and n = 16 (MBS) values per datapoint. Supplementary figure 7. Evaluation of the quality of the RNA -seq data for the 42 samples analysed in this study. Relationships of gene expression counts in replicate samples from liver (L; n = 10), brain (BR, n= 10), muscle (M; n = 10) and testis (T; n= 12) from adult wild (W) and early domesticate farmed (F) European sea bass. Pairwise dissimilarities between samples were calculated using the Poisson distance metric from the CRAN package PoiClaClu on raw coun ts and lower values indicate higher resemblance between samples. Samples BR.W2 and M.W5 were considered outliers and were discarded. n=5 independent replicates in all cases, except for farmed fish testis where n=7. The Poisson distance takes into account t he variance structure of counts when calculating distances. This is specifically designed for representing RNA -seq data as reported by Witten (2011) . Supplementary figure 8. Overview of gene expression differences in tissues of adult early domesticate vs. wild European sea bass. Volcano plots for genes expressed in a) brain, b) muscle, c) testis and d) liver, with the shrunk log 2 fold change shown on the X -axis and the - log 10 -transformed p-value on the Y -axis. Genes with p-adjusted <0.05 (red), log 2 Fol d Change > 1 or < -1 (orange) and those fulfilling both conditions (green) are shown. Independent replicates were as follows: n=5, wild liver; n=5, farmed liver; n=4, wild brain; n=5, farmed brain; n=4, wild muscle; n=5, farmed muscle; n=5, wild testis; n= 7, farmed testis. Supplementary figure 9. Validation of gene expression results obtained by RNA -seq with qPCR. Each datapoint corresponds to an individual fish and one of the following genes: adamts9 , mapk8a , ppargc1a and hspb11 in the muscle. Pearson’ s correlation (rho) and significance ( p) values are indicated. Independent replicates were n=5 for farmed and n=4 for wild fish, except for adamts9 where n=3 for wild fish. Supplementary figure 10. Differentially expressed genes (DEGs) in adult early d omesticate European sea bass. a) Gene Ontology (GO) term enrichment of DEGs with the most significantly altered GO terms ranked according to 1) whether they are under - or over - represented and 2) the decreasing order of -log 10 -transformed p-value of the enr ichment based on Fisher’s exact test. Colo rs indicate the percentage of DEGs that are members of each GO term category . Venn diagrams of genes containing differentially methylated regions (DMRs) inside their gene bodies or within a flanking distance of ±5 kb (blue) and DEGs (mustard) in b) brain, c) muscle, d) testis and e) liver. Independent replicates for gene expression estimation were as follows: n=5, wild liver; n=5, farmed liver; n=4, wild brain; n=5, farmed brain; n=4, wild muscle; n=5, farmed muscle ; n=5, wild testis; n=7, farmed testis and for DNA methylation n=3 per group. The number of DEGs that also contain DMRs is low, as in other studies (Kamstra et al. 2018; Uren Webster et al. 2018) . Supplementary figure 11. Principal Component Analysis of the DNA methylation data as measured by Reduced Representation Bisulfite Sequencing. The first two components explain 31.8 of the variance. Three replicates for brain, muscle, testis and liver were used and are plotted for wild (triangles) and farmed (c ircles) adult fish, as well as for the three pools of five eggs each obtained after natural spawning of captive fish. Supplementary figure 12. Effects of farming on the DNA methylation of genes in European sea bass adult tissues discussed in this study . DNA methylation (mean ± SE) of individual CpGs (arbitrarily numbered) around the differentially methylated regions (DMRs, shaded in grey) between wild (red) and early domesticate (blue) sea bass. Examples include a) col14a1a in brain, b) pcdh γ -a11 -like in liver, c) phldb1 in brain, d) foxc1 in testis and e) mapk8a in muscle. Supplementary table 1. Reduced representation bisulfite sequencing (RRBS) statistics 1 Fish origin Tissue Replicate Raw Reads Trimming (%) Alignment (%) CpGs CpGs > 10 reads Fold coverage Bisulfite conversion Farmed Eggs 1 25363386 99.64 86.40 1130220 859529 48.57 99.50 2 22514885 99.66 87.20 1106048 809291 44.51 99.50 3 22482506 99.61 86.50 1089627 780229 44.48 99.50 Mean 23453592 99.64 86.70 1108632 816350 45.85 99.50 Farmed Brain 1 20726415 99.61 87.50 1138697 771616 38.68 99.40 2 15629731 99.61 89.30 1092378 706289 30.59 99.36 3 12180912 99.59 86.80 991853 624057 27.66 99.42 Mean 16179019 99.60 87.87 1074309 700654 32.31 99.39 Farmed Muscle 1 59799884 82.48 82.20 1107093 828147 98.23 99.19 2 56155743 76.26 82.98 1190269 848329 74.15 99.37 3 36701374 84.48 79.71 1044515 773392 60.80 99.15 Mean 50885667 81.07 81.63 1113959 816623 77.73 99.23 Farmed
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