Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. e Han Lei targets drug evolution, potential their and into adaptation insights provide roundworms 266 panda of giant sequencing whole-genome and assembly Chromosome-scale hoe He Shaowen igWang Qing Yu ot ouaingntcaayi n rgsniiiypeito rvd nihsrvaigteipc fdwrighsoyon history the deworming to of prevention. impact adaptation disease the their were for revealing and phenotypes) insights importance roundworms provide lethal of of prediction population. to evolution structure sensitivity captive early linked genetic drug the a homologues population and inferring (essential in analysis for proteins genetic selection found reference Population target positive we unique host. drug strong pressures, a provides potential deworming under genome different 47 were The under and ced-7) addition, identified. targets and In drug bre-4 inferred known diet. nrf-6, genome, 23 panda-specific (glc-1, related schroederi Finally, giant genes B. families the the resistance-related gene to in significantly. four that adaptation metabolism expanded that the found acid have We for amino genome essential essential roundworm genes. be in the involved protein-coding to in genes predicted processes unique 19,262 information demonstrated and environmental for we Baylisascaris Furthermore, and of Mb organisms genome synthesis 253.60 important chromosome-scale importance chitin high-quality of are of epidermal a is size Roundworms to report panda genome we giant animals. Here, a the and host. in with the parasites humans schroederi to of of adapt study roundworms health The how the prevention. understanding and for to transmission threat disease mechanisms, a parasitic been studying long have diseases Helminth Abstract 2021 1, July 12 Copenhagen of 11 10 9 8 7 6 (CCRCGP) Park National 5 4 3 2 1 Lisby G,BGI-Shenzhen MGI, Sciences University of Zhejiang Academy Panda Chinese Giant of the University Reserve in Nature Animals National Rare Foping of Biology Conservation on SFGA of Laboratory Key BGI-Shenzhen BGI-Shenzhen available Genomics, not Agricultural Affiliation of Laboratory Key State University Forestry Northeast nvriyo Copenhagen University Biology, of University of Department Biomedicine, Molecular and Genomics of Laboratory BGI 2 uogWang Yulong , 11 unLiu Quan , 1 inigLan Tianming , 7 6 hnce Yang Shangchen , aqagZhou Yanqiang , 1 1 ase Kristiansen Karsten , eigSun Heting , 2 ehn Li Desheng , 1 8 ubn Han Ruobing , ii Zhu Yixin , 1 ogin Chai Hongliang , 3 amn Li Haimeng , 3 unLiu Huan , 2 utn Huang Yunting , 1 1 igigLi Lingling , 1 unigYang Huanming , 4 12 ihaDeng Linhua , n hjnHou Zhijun and , 1 ainLu Yaxian , 2 ioagCheng Xiaofang , 5 hwiPeng Zhiwei , 2 u Xu Xun , 1 1 arn Lu Haorong , 9 10 Jieyao , Michael , 3 , 2 , Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. Chai Zhu Yixin Zhou Yanqiang targets insights Han drug provide Lei roundworms potential panda and giant adaptation 266 evolution, of their sequencing into whole-genome and assembly Chromosome-scale onwrsadteraatto otehs.Pplto eei nlssaddu estvt prediction sensitivity drug of and evolution analysis early genetic the Population inferring different for host. drug reference under the potential unique 47 addition, to a and adaptation In provides targets their drug genome known and The diet. 23 roundworms ( Finally, identified. panda-specific genes population. were giant captive proteins resistance-related a the target in four the selection to that positive in adaptation strong found metabolism under the we acid for pressures, amino essential Furthermore, deworming essential be significantly. in expanded to involved and have synthesis genes inferred chitin report genome unique epidermal we roundworm to demonstrated Here, the related we families host. in gene the processes that to information found We adapt environmental parasites roundworms genes. how of protein-coding understanding predicted study of 19,262 for The genome important importance chromosome-scale are prevention. of Roundworms high-quality and is a animals. transmission panda and giant disease humans of the mechanisms, health in parasitic the studying to threat for a organisms been long have diseases Helminth Abstract [email protected] * + 15 14 China 150040, Harbin 13 12 11 10 9 8 7 6 5 China 611800, Sichuan (CCRCGP), 4 Denmark Copenhagen, DK-2100 3 2 1 Hou Zhijun orsodn uhr:huhjnz13cm iha@eoisc,[email protected] n li- and [email protected] [email protected], [email protected], authors: Corresponding China. 518083, Shenzhen China BGI-Shenzhen, 518120, GeneBank, Shenzhen National BGI-Shenzhen, Write, China China and 100049, Read Genome Beijing of Sciences, Laboratory of Key Provincial Academy Guangdong Chinese China of Province, University Technology, Guangdong Future Foshan, University, of Foshan School China Engineering, Park 150040, and National Harbin Sciences Panda Administration, Life Forestry Giant of State School the China Conservation, in Wildlife Animals of Rare Laboratory Key of Biology Conservation on Copenhagen, SFGA of of University Laboratory Biology, Key of Department Biomedicine, Molecular and China 518083, Genomics Shenzhen of BGI-Shenzhen, Laboratory Genomics, China Agricultural 150040, of Harbin University, Laboratory Forestry Key Northeast State Area, Protected and Wildlife of College hs uhr otiue qal oti work. this to equally contributed authors These oigNtoa aueRsre azog730,China 723400, Hanzhong Reserve, China Nature 266555, National Qingdao Foping Sciences, Administration, Life Grassland for and Institute Forestry Advanced National Qingdao-Europe Diseases, Wildlife of Surveillance for 518083,China Station Sciences,Shenzhen of General Academy Chinese of Center,University Education BGI China 518083, China Shenzhen 310058, BGI-Shenzhen, Hangzhou MGI, University, Zhejiang Sciences, Life of College 1 unigYang Huanming , 1,5+ 12 1,5* inigLan Tianming , utn Huang Yunting , 1 ubn Han Ruobing , 2 u Xu Xun , 2,3+ 8,9 1 ehn Li Desheng , ioagCheng Xiaofang , igigLi Lingling , 2,8 ihe Lisby Michael , 1 4+ alssai schroederi Baylisascaris ainLu Yaxian , amn Li Haimeng , 11 iyoYu Jieyao , 3 unLiu Quan , 2 1 arn Lu Haorong , 2,7 ihaDeng Linhua , 8,9 1,6* uogWang Yulong , ase Kristiansen Karsten , glc-1 ihagnm ieo 5.0M and Mb 253.60 of size genome a with 8,9 igWang Qing , , 4 nrf-6 hwiPeng Zhiwei , 1 eigSun Heting , , bre-4 .schroederi B. 12 hnce Yang Shangchen , 3,14* and 1 hoe He Shaowen , unLiu Huan , 13 ced-7 Hongliang , genome, were ) 2,3* 15 10 , , , Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. fdu eitne ial,ptnildu agtpoen eeietfid hc rvdsnwisgt into insights basis new provides genetic which potential identified, the were as proteins well of of as target management adaptation panda, drug disease the giant potential potential Finally, the the of of mechanisms resistance. diet genetic drug specific of possible the explored especially chromosome-scale we environment, a intestinal genome, report we the Here, on al.). Based et of (Xie mechanisms infections of genetic of genome of control reference exploration and in-depth prevention preventing further analyses, and gene adaptations multiple or single and anthelmintic- morphological become potentially may variants Although These of survived. development a had that anthelmintics pathogens. indicating of increased resistant 2015), variety of Deng, a & the problem to He, in the resistance regularly Li, occurred Moreover, (D. are anthelmintics had captivity with subtypes 2014). in treatment drug-resistant al., after pandas days investigations, Giant et 15 to Li underestimated. to According 10 D. seriously days). be 2018; 60 to al., (every likely dewormed et is Hu anthelmintics (H. to resistance populations the captive challenges This and panda, wild absorption. (short giant and characteristics digestibility the intestinal low of with carnivorous data diet typical a of have bamboo, absorption pandas eat nutrient Giant but intestines), pandas. small Casarosa, 2006; thick species giant (Schaul, and & Baylisascaris of rupture by roundworms, Malloggi, intestine bowel Infection other fatal small Renzoni, 2011). with even the Papini, al., and Compared blockage, et 1989; severe 1998). intestinal Zhang Yang, baylisascariasis, even Boyce, L. GY severe and 2006; M. cause Ellis, (NLM) addition W. & in migrans & Janssen, can larva Zhang, Kazacos serious including neural Zhang, cause R. syndromes Wildt, (OLM), may different (K. 1995; migrans with organs hepatitis larva associate different and ocular small being to pneumonia (VLM), larvae the species roundworm migrans of in into different larva hatch Migration mature with visceral under they eggs organs, 2018). where infective the the intestine Tao, become the panda, to & can to damage a (Wang returns eggs eventually by worms Fertile and ingested reproductive organs, soil. several adult being the to after migrate in not larvae and periods the though (12˜22) intestine, extended Even and for conditions 2005), risks. survive temperature or safety Berlin, can suitable patent Lock, and and & of (Wolf, as resistant health cycle Ash, birds very infection public life Shafir, 1989), are the potential cause Boyce, Sorvillo, of with M. also Wise, details W. parasites 2002; species & all zoonotic (Murray, Baylisascaris Kazacos considered humans (K. therefore and 2003). mammals are 2007) of al., Garner, variety intermediate et a & an Silva in Carpenter, through De (LM) passing migrans without 2006; larva panda al., latent giant et the infect (Bethony for directly host implications can far-reaching and and nematode soil-transmitted broad with risks schroederi pathogens Baylisascaris possible detecting and with easily identifying health. deal are for human to relevance eggs and In-depth of actions helminth wildlife soil. information appropriate soil-transmitted or provide feces instigate can period, contaminated wildlife and through incubation in humans long Boyce, helminths to M. even the of and W. and result, studies & distribution livestock, a Kazacos and wide (K. As wildlife greater its between been infections. transmitted never to helminth have of wildlife Due interface, in transmission land-urban isolated (Hotez, for 1989). once wild worldwide barrier diseases the wildlife of effective and transmission and an cities, for livestock towns, longer risks humans, of no expansion of is the health isolation With the geographic to 2009). threat Molyneux, & a Savioli, been Fenwick, long has ascariasis Parasitic importance 1 of structure genetic population on Keywords: history deworming of prevention. disease impact for the revealing insights provide | INTRODUCTION .schroederi B. alssai schroederi Baylisascaris .schroederi B. .schroederi B. oe het obt idadcpiegatpna,cretsuisaelmtdto limited are studies current pandas, giant captive and wild both to threats poses aaii eaoeseicfrtegatpna( panda giant the for specific nematode parasitic a , .schroederi B. .schroederi B. hc sas h rtcrmsm-cl eeec eoeo ascaridoids. of genome reference chromosome-scale first the also is which , Baylisascaris o uvvli h ml netn.Bsdo vial epidemiological available on Based intestine. small the in survival for onwrs dpain eei iest,Anthelmintics diversity, Genetic Adaptation, Roundworms, , stelaigcueo et rmpiayadscnayifcinin infection secondary and primary from death of cause leading the is aebe salse,i skonta gsscee ihfeces with secreted eggs that known is it established, been have .schroederi B. n eae roundworms. related and 3 .schroederi B. .schroederi B. ouain n that and population, ssalri ieadi anyfudin found mainly is and size in smaller is gscnsilb eetdi h feces the in detected be still can eggs iuooamelanoleuca Ailuropoda .schroederi B. .schroederi B. ainswith variants othe to ,i a is ), Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. eaetasrpoesqecswr lge otegnm o sebyuigTpa v..)(Trapnell, (v2.1.0) TopHat using assembly for genome the to aligned were sequences transcriptome protein-coding female the a anno- selected we sequencing-aided ( annotation, RNA homology-based species pocapsae and For homologous search prediction. five homology-based gene of prediction, perform sequences to gene used novo was de tation of strategy combined A LTR G.), & schroederi For as (such bacteria the to against blasted genome that the blast scaffolds used to the software next lactis deleted (v0.9.10) We v180322) then diamond (3D-DNA database, the data assembly used NR described. 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FINDER .canis T. ihntrlyaqie netosfo h hn osrainadRsac etrfor Center Research and Conservation China the from infections acquired naturally with ) eoewsasmlduiga“orc-hnasml”srtg.Frt NextDenovo First, strategy. “correct-then-assemble” a using assembled was genome rmNB hts/wwnb.l.i.o/.FrRAbsdpeito,aml and male a prediction, RNA-based For (https://www.ncbi.nlm.nih.gov/). NCBI from ) .schroederi B. rgamalayi Brugia ouainwr olce rmtegatpna( panda giant the from collected were population , 4 .schroederi B. .elegans C. a sdt orc n sebeadatgenome. draft a assemble and correct to used was ) , rsinhspacificus Pristionchus eoet hoooelnt scaffolds chromosome-length to genome usppln Ga ta. 00 to 2020) al., et (Guan pipeline Dups .schroederi B. shrci coli Escherichia , tienm car- Steinernema ouainwere population o , ni use. until C Lactococcus Ailuropoda B. Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. 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Data may be preliminary. obte nesadteaatto oteseichbttaditsia niomn ftegatpanda, giant the of environment intestinal and habitat specific the to adaptation the difference understand significant better To most the the 2c). that for (Fig. showed roundworms accounted analysis in enrichment adhesion 3.5 expansions GO biological exhibiting family actin families and 2b). the gene behavior families, all (Fig. gene nematode Coghlan among roundworms expanded (A. to of four chymotrypsin/elastase proteases statistics related host all number the from copy genes among of the roundworms expanded to of expansion significantly according protection an addition, is a In observed to 2018). related we al., be study, et may previous which family, a gene ( with inhibitor observed consistent was (ko04015) self-defense, pathway signaling to Rap1 and (ko04145) pathway some ( branch roundworm ofe ieadtoerltdt aaii iei eaoe.Frbt h xaddadcnrce gene protein contracted to chitin-binding and compared the branch expanded that roundworm the the found Interestingly, and both in we S13b). 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Data may be preliminary. ahaso seta mn cd seilytedgaaino aie ecn n sluie(ko00280, isoleucine and that leucine found valine, we of Finally, 3.6 degradation 3b). the especially (Fig. acids behavior < amino eating essential of of regulation pathways positive in pathways, involved metabolic schroederi family in actin gene involved the ko00980; the genes P450, of of of cytochrome expansion number ko05100; by significant the xenobiotics (ko05130, highly that of munity showed the (metabolism enrichment to metabolism KEGG due drug including largely 3d). term was 3a, GO which enriched (Fig. significantly contraction, family most muscle The straight (GO:0006941), process (GO:0030036). the contraction metabolic organization was chitin cytoskeleton muscle (GO:0030536), actin striated behavior and in feeding (GO:0006030) involved larval functions (GO:0002119), development with larval families nematode gene expanded identified We in genes contracted , and expanded the analyzed we useisad2 ape rmidvdaso h idQnigpnasbpce Fg a.Teaverage The A 6a). S13). and (Fig. S1 (Table subspecies respectively panda 41-fold, Qinling and wild 97.91% Sichuan reached the the depth of of sequencing pandas individuals and captive from coverage from 240 samples sequencing including 26 samples, and 266 of subspecies resequencing whole-genome out carried We effective the of changes the estimate both to of model size (PSMC) coalescent population Markovian sequentially pairwise the used of we history demographic the reconstruct To family actin the of expansion significant by very ( controlled a family is observed Rho polymerization We the Actin and 2017). of 4a). 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(MSMC) Kya Period low pinnacle but Coalescent (300-130 historical their Lake Markovian 5a), a reached periods Greatest reached species glacial also size the (Fig. two roundworm Pleistocene population Kya in the the two effective of 10 occurred The last size to change the population lag. ago) obvious effective slight during the years a significantly and showed (thousand declined Kya), roundworms Kya 50-10 panda the 300 giant of size from the population trend of ( effective same sizes of the change population the exactly effective the almost that have showed panda analysis PSMC 2011). 3.7 the in selection positive strong under 3a). be Data to shown was acetylcholine 2007), the Sattelle, roundworms, (P=6.5x10 & three deg-3 with alpha-type Compared subunit 3a). receptor Data implemented (Supplementary model roundworms branch-site three the the other Using with in interaction. genes myosin-actin 1999). 475 on M., PAML, effect & in (Maekawa possible reorganization a cytoskeleton suggest actin finding rho-induced These promote to cofilin phosphorylates then .univalens P. .1 i.3c). 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(Fig. changes significant exhibited 0.01), .schroederi B. .schroederi B. n h in ad ihntels n ilo er(.L Durbin, & Li (H. year million one last the within panda giant the and eoewr on ob ne togpstv eeto compared selection positive strong under be to found were genome .schroederi B. -3 ,wihi nipratdu agt(oe,Dvs Hodgkin, Davis, (Jones, target drug important an is which ), populations .schroederi B. P 9 < 0.01). n xlr h eainhpwt h in panda, giant the with relationship the explore and , ROCK oprdwt he onwrs( roundworms three with compared Ne hshrltsteLMkns which LIM-kinase the phosphorylates .schroederi B. of ) .schroederi B. RhoA eoe(Supplementary genome P , Rac1 < n h otgiant host the and .1 n autoim- and 0.01) Rac1 and , .suum A. , Cdc42 ROCK B. P ; Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. nraeo eitnei onwr ouain D ie l,21) nadto okondus ewere we drugs, the known by to compromised addition In are anthelmintics 2015). existing al., Many et Li 2015). (D. al., populations et roundworm Wang against in (C. effective resistance ivermectin be of to and proven increase databases been al.) 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Data may be preliminary. adsatrteamnsrto feitn nhlitcdus(.Wn ta. 05.W bevdarecent a observed We 2015). drug al., widespread et Wang to (C. leading drugs anthelmintic population, drive existing the may of in drugs administration resistance of the from use after drug shifted Frequent pandas has to the 2008). decades related al., recent in genes et in resistance of Zhang pandas frequency giant (J.-S. basis of deaths increasing genetic death VLM-related the the of to explain cause poaching extent, the and some investigation, starvation previous to a least of to at epidermis may, migration According nematode family the and of of gene to contraction ability repair actin significance muscle locomotion the the great stronger for of in of of involved force expansion is is The driving which actin panda. the 2012), that giant provided Chisholm, shown have & have may (Suhong Studies damage family 1998). actin (Hall, the movement of cell of migration selection and movement positive (KO00280; the the and in isoleucine In role and important 1997). leucine bamboo of very Wei, valine, the ability & of to the Yuan, degradation enhance response Hu, the in (Zhou, especially evolved evolution of acids, gradually families of has gene years panda unique et of several giant Williamson the millions The 2011; similar, during al., are traits. diet et species evolutionary (Soblik Ascarididae molecular viscera of unique in characteristics in larvae morphological collagen of the digest migration Although can the epidermis that in nematode tissue shown involved the in have 2006). be in involved al., thus studies astacins potentially and of Previous genes tissues, products to homologous Some host respectively. secretory genes return the kinase, including finally eggs. in roundworms, develop, serine/threonine-protein lay wall, in metallopeptidase(s) and and and intestinal expanded molt significantly mate, the metallopeptidase 1989), been adults, penetrate Boyce, to have harsh evasion into M. intestine, a immune W. develop the and in & to enter invasion even Kazacos intestine larvae roundworms (K. small stage, significant of organs the a parasitic survival and observed the the tissues have among prolonging in We migrate thereby addition, 1970). eggshell, (FAIRBAIRN, which In roundworm years shell, chitin ten environment. the polysaccharide to of elastic protein up formation and for chitin-binding the tough soil the adap- a the the have of in roundworms reflecting expansion persist of useful nematodes to Eggs and free-living eggs valuable life. from enables expulsion. parasitic different a for the provide are development to drug that will tation as characteristics genome well special this as have that roundworms, Roundworms chromosome-scale envisage on first We research the future present Ascarididae. for we study, in resource this contiguity genetic In best 1). the (Table respectively with the kb, of 375 assembly and kb genome of published 1,825 of studies kb, N50s In-depth 290 scaffold are The 1998). al., sequence. genome et high-quality (Zou pandas giant of schroederi possible B. at provide will anthelmintics. compounds new 4 and of proteins, targets development the drug the all potential for Among point These ( starting target anthelmintics. 4b). genes each as Data target against designed (Supplementary the three approvals compounds originally being of available that not for potential potential commercially found were encoding greater target the have we for compounds drug drugs evaluate the searched these above to all and we although of III factors anthelmintics, position protein Phase main the existing new located the six we into Since Finally, considering developed 8). 8). ‘0/1’ (Fig. Fig. of superscaffolds methods; on score (see genes against target a blasting drug that By sat a targets as we 2018). protein ChEMBL al., Then et protein Coghlan proteins. single (A. complexes single on protein focused than (similarities We against proteins drugs target develop targets. to drug easier potential be may new identifying to committed | DISCUSSION xiissrn niomna dpaiiyadwd itiuin n satra otehealth the to threat a is and distribution, wide and adaptability environmental strong exhibits .schroederi B. .schroederi B. .schroederi B. > 0)i h igepoendtbs hML eietfid9 ee encoding genes 95 identified we ChEMBL, database protein single the in 80%) .schroederi B. ouain utemr,teehv enrprso ieeet ngiant in effects side of reports been have there Furthermore, population. .schroederi B. cmd-1 oasr uret.Atnpooe ucecnrcinadpasa plays and contraction muscle promotes Actin nutrients. absorb to ihtesaodN0o 23 b ersnigagnm assembly genome a representing Mb, 12.32 of N50 scaffold the with CPG-2 , Ap2s1 eefudt eivle ntemtbls fesnilamino essential of metabolism the in involved be to found were hnohrroundworms. other than aiyi onwr rnhs hc a erltdto related be may which branches, roundworm in family , HRAS 11 .schroederi B. .schroederi B. aeaalbecmonswt hs III/IV Phase with compounds available have ) .suum A. ntehs.Tesgicn expansion significant The host. the in aebe aprdb h ako a of lack the by hampered been have , .univalens P. P < .schroederi B. .1,wihi ieyto likely is which 0.01), .schroederi B. and .schroederi B. .canis T. tl shows still genomes genome, nthe in Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ..adTML rt h aucitwt nu rmZJH,KK,ML,DSL,HL,QL,HMY and manuscript. H.M.Y. final Q.L., H.L., H.L., the project. D.S.L., approved D.S.L., the M.L., and M.L., K.K., supervised read Z.J.H., Q.L. K.K., from and authors Z.J.H., input K.K. All with H.L., manuscript. manuscript Z.J.H., manuscript. the the X.X. S.C.Y. wrote the wrote and T.M.L. supervised and Y.X.Z., and X.X. T.M.L. Q.W., L.H. DNA and the R.B.H., L.H., and performed H.M.Y. H.M.L., H.L.C., H.R.L. analysis. T.M.L., Q.L., and H.T.S., L.H., data J.Y.Y. Y.L.W., the Y.Q.Z., sequencing. S.W.H., Y.X.L., performed and D.S.L., L.L.L., Z.W.P., construction L.H., library X.F.C., project. extraction, the samples. the initiated collected and L.H.D. designed H.L. and Z.J.H., of Laboratory CONTRIBUTION Key 2017B030301011). AUTHOR Provincial No. Guangdong the (grant the in Forestry Write and Animals State and KLSFGAGP2020.002), Rare of Read of (No. Laboratory Genome Biology Park Key Conservation National on Park of Panda Foundation Administration) for National Giant Park the Funds (State Panda China, Research Administration of Giant River Fundamental of Grassland 2572020AA30) Pearl The and (2019CX01N111), Project the (No. in Province Universities 20180302), Open Animals Central Guangdong (No. 2017YFD0501702), the in Rare project Program of research (No. technology Recruitment Biology Program Talent and Conservation R&D science Forestry on Key No.2020004), SFGA National (CCRCGP, of the by Laboratory supported Key was on work history This deworming popula- of drugs. addition, anthelmintic impact novel the In the of epidermal revealing ACKNOWLEDGMENT development in insights in future loss metabolism. provide involved and or acid prediction structure genes selection genetic drug amino including gene population and essential environment, of analysis and intestinal details genomics the information, the tion to study environmental to adaptation synthesis, possibility and evo- chitin host a evolution accompanying provides of hosts genome specific process roundworm to The adaptation evolutionary remarkable lution. a undergone diseases. has parasitic Roundworms other works and such baylisascariasis that of novel envision treatment We as and prevention 5 testing. repurposing the further for of for needs considered activity 90 modalities compounds anthelmintic be new of target the provide could Nevertheless, potential total will compounds other a expenses. and These and identified compounds effort approval. drugs. We these Supplementary considerable follow-up 3/4 save chlorpromazine; of phase level. would development and which a the genome anthelmintics, have trifluoperazine for whole that basis haloperidol, the al., a 4b) (lonafarnib, providing et at Data compounds targets, Wang screened four drug side (C. potential searched be serious use 95 We can of efficacy, and targets frequency targets low drug new increased drug from known for to and suffer need of due drugs, drugs pressing genome populations chromosome-scale specific a existing parasite The is since in there . resistance panda, Specifically, 2015) drug giant Hudson, 2012). rising (James, the Zhou, or roundworms protect & of effects expulsion King, to intestinal Utzinger, drugs for Melville, drugs anthelmintic Jia, anthelmintic new 2009; Davey, for individuals need & drug-resistant urgent of an Hui, still detection is & that There is the (Zumla shown works. and genes have pathogens future the genes antibiotic-resistant in Studies these in drug-resistance potential essential of individuals. selection of into still frequency resistant evolve identification natural are gene even of the of may increase the Therefore, degree infection The and that the 2019). of emergence possible Although sources the genes. is new decades. cause may resistance-related it some may recent This quantified, few it in populations. be and a drugs captive cannot increasing, of of in areas use genes trends frequent resistance deworming, resistance-related selection current the for drug natural to pressures of evaluating related selection frequency different be for increased completely an option facing changes indicated an recent are results considers offer populations mainly two thus, analysis The selection and natural frequency. Sichuan), gene and in (Qinling regions different two from nrf-6 of selection positive significant | CONCLUSIONS , pgp-3 and bre-4 ncpie(C ouain.Atog idadcpieppltoswr obtained were populations captive and wild Although populations. (SC) captive in ) ABC and CYP .schroederi B. aiymmesadohrrssac-eae ee ( genes resistance-related other and members family 12 rvdsarfrnefrtedvlpeto species- of development the for reference a provides glc-1 , Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. hn . u . u,J,&Jag .(03.Scee rti rdcinsse obnn CJ-SPHMM, combining system prediction protein the Secreted for (2003). Kit Y. Tool Jiang, A & PSORT. MAKER-P: J., and Luo, TMHMM, (2013). P., M. Yu, Annotations. Yandell, Y., Genome & Chen, Plant C., of J. Control Stein, Quality (2009). 513. C., L. 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(Family: bears of populations free-ranging and captive in transfuga Baylisascaris eaooy 19 Nematology, uli cd eerh 25 Research, Acids Nucleic 1,70-80. (1), 3,559-575. (3), 52) 895-898. (5429), 1,1-7. (1), rceig fteNtoa cdm fSine,109 Sciences, of Academy National the of Proceedings oatsFudto ypsu,247 Symposium, Foundation Novartis (8). uli cd Research Acids Nucleic Bioinformatics icii,90 Biochimie, 5,955-964. (5), 17 8,1176-1177. (8), uli cd Research Acids Nucleic 2,p.243-259. (2), (suppl aastlga 36 Parassitologia, ) suppl 2), 91-103. , 2. W) W1. (W1), 3,321-329. (3), aue 449 Nature, 2) 9917-9922. (25), mrcnJournal American eia Reference Medical aue 419 Nature, Clinical Nucleic (7164), Plos Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ag . ag . ear,J . a,X,L,J,Wn,X,...Go .(02.MSaX toolkit a MCScanX: (2012). H. Guo, . Pandas Giant . collinearity. of and . Shock synteny Toxic X., Wang, gene (2015). J., of M. Li, analysis Li, X., evolutionary e49-e49. Tan, . Species. and D., a . detection J. of DeBarry, . for Conservation H., Y., Tang, Zhi, the Y., W., in Wang, Huang, Factor L., Risk Li, Ivermectin. A F., by Shen, Caused Panda: J., Giant Lan, C., the Wang, of Parasites 99 Parasitology, (2018). in Advances parasitic Tao. in & metabolism of Wang, analysis Comparative (2018). M. Mitreva, RNA-Seq. & J., with worms. Parkinson, junctions S., splice Seshadri, R., discovering Tyagi, TopHat: L. S. Salzberg, 25 & matics, In L., Pachter, C., RepeatMasker. Trapnell, understanding and Nikolskaya, Using eukaryotes. . includes Springer. . (2012). version . S. updated V., E. an Tempel, Koonin, B., database: Kiryutin, COG R., The A. 41-41. Jacobs, D., (2003). J. N. Jackson, D., A. N. Fedorova, L., Genomic R. Tatusov, in Elements Repetitive Identify to RepeatMasker 4 Using (2009). N. Sequences. Chen, & G M., A Tarailo-Graovac, N. elegans. (2012). C. D. Brattig, Everyone. in A. for closure Discovery Chisholm, wound . Ligand & – X., . 15 Suhong, ZINC . (2015). F., Modeling J. & Geisinger, J. Strongyloides mation Irwin, from M., & Excretome/Secretome Kirchner, T., the Y., Sterling, of B. Analysis Proteases. Proteomic Renard, Stage-specific Stage-resolved M., of Cycle ratti—Identification Mitreva, Life E., 1 (2011). A. May, W. Accessed Younis, Last H., org, 2008–2015. repeatmasker. Determination Soblik, Open-1.0. httpwww. (2007). RepeatModeler from: J. (2015). B. Available P. Rude, Green, Biology. & & Systems R., R., J. pandas. Hubley, Ouellette, giant A., S., by Smit, R. output Sikes, fecal A., BUSCO: and H. digestibility Bissell, (2015). bamboo-diet L., (2015). M. of J. Parsons, E. E. A., Zdobnov, Barillot, J. orthologs. & Sims, single-copy . V., with E. completeness . 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Andreas board, editoral / bioinformatics in protocols Current m eois 14 Genomics, Bmc aueGntc,46 Genetics, Nature 2324. , hns ora fWildlife of Journal Chinese 4,589. (4), urn ilg,21 Biology, Current 1-33. , 1,923. (1), . 8,919-925. (8), α -asgaigptwypooe ci-eitdepidermal actin-mediated promotes pathway signaling q-Ca oeua ellrPoemc,10 Proteomics, Cellular & Molecular 2,1960-1967. (2), . 18 ru,18 Ursus, oieGntcElements Genetic Mobile eoebooy 16 biology, Genome 1,38-45. (1), uli cd eerh 40 Research, Acids Nucleic m iifrais 4 Bioinformatics, Bmc ora fCeia Infor- Chemical of Journal etl,UA nttt for Institute USA: Seattle, 2018. , 1) M111.010157-. (12), Bioinformatics 1,259. (1), p.29-51): (pp. Bioinfor- (19), (7), (1), Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. o,Xnha,Wn,Amn eg ui,...Knj.(98.Lta atr fdsae n protective and diseases of factors Lethal (1998). Kongju. . pandas. Min, Giant . . penned and . . wild Lujin, . of G., Zeng, canis. countermeasures Samson-Himmelstjerna, Aimin, Toxocara Von Wang, pathogen P., Mabian Xinghuai, Nejsum, zoonotic in Zou, D., the behaviour N. of feeding Young, blueprint and H., Genetic Cai, habits (2015). K., food P. J. pandas Korhonen, Giant Q., X. (1997). Zhu, F. Wei, & Reserve. C., Natural Yuan, Dafengding J., Hu, C., Zhou, LTR sequencing Whole-genome (2007). (2013). W. W. Hao, transposons. Fan, & . adaptation. X., . local Zhao, and . history X., individual- Guo, demographic pandas: Q., into giant Wu, insights 67-U99. of X., provides parasites Zhan, pandas The S., giant Dong, (2011). of P., F. Zheng, Wei, S., & Zhao, Y., Hu, animals. X., wild threat Gu, in Parasite H., measurement Wu, (2008). based S. X., Yang, Zhang, L., & M., Zhang, A. Kilpatrick, G.-Y., conservation. 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Baylisascaris R. transporters. H. ABC (2007). to Horvitz, M. similar & M. C., Garner, update Y. & major Wu, A W., 5.0: J. moluccensis). DrugBank Carpenter, central (Cacatua (2017). B., Cockatoo fatal M. Moluccan Lock, and Wilson, N., & Severe J., K. E. Wolf, (2005). 2018. Lo, for G. G., database C. O. DrugBank An, Berlin, the D., raccoons: to & Y. of Feunang, roundworm R., S., common D. L. the Wishart, Ash, procyonis, literature. Baylisascaris C., current by S. of caused review Shafir, humans a J., in is disease (2006). F. A. system larvae, Sorvillo, Loukas, nervous hookworm E., . infective M. . by Wise, . secreted S., Mendez, metalloprotease migration. J., astacin-like tissue Plieskatt, in an V., (2006). involved Deumic, MTP-1, S. Y., caninum Ellis, Oksov, S., & Ancylostoma Lustigman, L., L., D. A. Williamson, Janssen, H., Zhang, management A., and Zhang, medicine E., D. Wildt, 2,327-335. (2), 482 uli cd Research Acids Nucleic 12,0-67. (1-2), chat,5 Ecohealth, ee 482 Gene, abig nvriyPress. University Cambridge : ora fScunTahr College Teachers Sichuan of Journal el 93 Cell, neto n muiy 74 Immunity, and Infection irbsadIfcin 7 Infection, and Microbes 6. , 12,0-67. (1-2), 1,6-9. (1), uli cd eerh 46 Research, Acids Nucleic ora fWllf iess 47 Diseases, Wildlife of Journal IDR necetto o h rdcino ullnt T retro- LTR full-length of prediction the for tool efficient an FINDER: (suppl 6,951-960. (6), ora fAinMdcn ugr,21 Surgery, & Medicine Avian of Journal ) suppl 2), ora fFrsr eerh 002 Research, Forestry of Journal 19 2. 2,317-323. (2), 2,961-967. (2), Dtbs issue). (Database . oeua n iceia parasitology, biochemical and Molecular 1,164-171. (1), 6 in ads ilg,veterinary biology, Pandas: Giant 2,6145. (2), aueGntc,45 Genetics, Nature hnJVtSi 18 Sci, Vet J Chin 3,220-225. (3), 19) 77-80. (1998), Actacentiarum (1), , Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. eeiiesqecs()95 . 13.5 39.95 - 39.07 4.4 37.85 317,115,901 3,511 66,363; 253,353,821 5,747 13,874; - 2,991 204,976; 265,545,801 37.26 6,918 16,980 198,864; 375,067; 10,466 (5.82%) 48,674; 18,474,532 20,376 1,825,986; (0.38%) 966,507 6,506 8,420; 46,632 290,558; (0.7%) 1,980,846 281,639,769 ( 15,567 7439 2,778; 104,281; 9.53 (4.70%) 13,257,555 37.30 42,126 888,870; 192,063 6,864,504; 1,221,088 253,610,985 12,324,682; # (0.10%) 261,088 - (%) 536 sequences 75; Repetitive (%) content GC (bp) Genome Contigs Scaffolds; of (bp) N90 Contigs 436,058 Scaffolds; genome) 3,381,480; of of N50 % (bp; (bp) length Contigs Gap Scaffolds; of length Average Contigs Scaffolds; of Number (bp) size Genome Description the of features the of Summary overview. 1. global Table diseases: infectious reemerging and Tables Emerging (2019). S. 33 D. Clinics, Disease Hui, & A., Zumla, h au fsaitclSdksmlil oprsn et fepninadcnrcino ee comparing ( of in genes contraction contraction) of and contraction represents Expansion (or and Fig.3 asterisk expansion expansion red of significant The tests with comparisons genes. multiple contraction) family Sidak’s (or with gene statistical expansion roundworms; of the of value in number p in families total enrichedthe gene genes the are expanded to functional that significantly compared pathways KEGG GO roundworms the KEGG of top of top with number proportion the the compared copy The represent represent Ascariasis gene triangle triangle of and enrichment open families solid function the gene the and contracted with and compared circle the Ascariasis circle open in of The families solid gene families.(a) respectively. The expanded the , gene in families enriched roundworm families. gene are that gene of of pathways number roundworm contraction the in and represent decreases expansion nodes the The below Fig.2 numbers respectively. The contracted, intersection. and bifurcations. each maintained, in the expanded, count significantly at family intersection shown gene the total are represent the times rows indicates the barplot between The lines vertical (d) species. edge. and between circles families the Black expanded to of nematode. center a the represents row from Each scaffolds blocks. and synteny coverage and different sequencing characteristics content, GC genomic (b) content, and repeat nematodes number, gene six among of relationships synteny phylogenetic The Fig.1 LEGENDS FIGURE hra h xsrpeet h families. the represents axis y the ( whereas contracted terms. or GO expanded of significantly similarity genes). semantic in (background on families pathway based gene is the in bubbles expanded in the significantly genes of for all position items The to GO over-represented genes) significantly (target of pathway clusters the in located genes of families gene expanded .su .univalens P. suum A. h ulse eoeifrainof information genome published The .schroederi B. ytn of Synteny ieclbae aiu ieiodpyoeei reo i eaoe.Teetmtddivergent estimated The nematodes. six of tree phylogenetic likelihood maximum Time-calibrated .elegans C. .schroederi B. .schroederi B. or suiu eefamilies. gene unique ’s .hapla M. 4,xiii-xix. (4), (c) .schroederi B. and Oeatrs ersn 10 represent asterisk (One .(a) pe ltsoigteitreto fgn aiyepnin nnematodes. in expansions family gene of intersection the showing plot Upset with .canis T. eoi hrceiainof characterization Genomic .univalens P. P .schroederi B. .schroederi B. .schroederi B. < h rprinrpeet h ai ftenme fexpanded of number the of ratio the represents proportion The . (d) .(a) ). .1.Texai ersnstefu onwrso Ascariasis, of roundworms four the represents axis x The 0.01). .schroederi B. eta hwn h eefmle of families gene the showing Heatmap and niheto h EGptwyi oesignificantly some in pathway KEGG the of Enrichment 20 eefmle oprdwt he roundworms three with compared families gene .canis T. -1 genome. ntrlae)(.H ta. 2020). al., et Hu (Y. released) (not ). ti study) (this .elegans C. .schroederi B. ttegn ee.Dffrn oosrepresent colors Different level. gene the at or (c) .schroederi B. .hapla M. niheto EGpathways KEGG of Enrichment eoe h gr hw the shows figure The genome. infiaticessand increases Significant respectively. , .schroederi B. .elegans C. # > 00b)3,3;4,0 ,7 287 51,969 22,857; 1,274 40,509 31,538; bp) 1000 .schroederi B. (b) or Infectious REVIGO .hapla M. htare that (b) .umP nvln .canis T. univalens P. A.suum GO (c) . Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. i. nlsso aua eeto ncpieppltos (a) (QLI) wild (b) populations. and captive (SC) in captive in selection ( individual’s signals the natural individuals. of sweep different proportion of the tion the quantifies shows axis Analysis axis y x The Fig.7 and 5). population, to 2 ancestral from inferred (K from populations used genome QLI We and SC information. of structure SNPs (QLI) whole-genome Qinling using to comparison constructed populations; in two of (SC) analysis Sichuan PCA of relationships (a) and population. structure Population 6 ( Fig. generation per rate population. mutation ( Sichuan sizes neutral population The effective ( respectively. loess. years, Chinese 12 sequence and original the 0.17 schroederi from were resampled panda randomly giant sequences 100 for estimates It schroederi (PSGs). B. genes (a) selected sexual polymerization. genomes. positively through the actin resequencing are in of worms involved history red adult families Demographic in into gene Fig.5 migration key genes develop organ three and and internal of intestine polymerization, expansion of small actin significant stage shows the in the involved to represent are return L4 pathways larvae and L5 L3 Stage maturation. stage. larva. infective the the into of developing after body of history of history Life Fig.4 rti a tutr ntePB.Ptnildu agtpoen noiggnso ahsuperscaffold each on genes encoding proteins target drug Potential (black). marked The alignment PDBe. (6) are conserved (EP); the scores protein highly in corresponding the excretory/secretory a and structure predicted criteria, having A condition. a six (5) mismatch targets has chokepoint; the protein indicating drug metabolic represent predicted circle known A targets hollow ChEMBL (4) drug a phenotype; with potential and Similarity the condition (1) following match ( were: indicating circles criteria circle The formulas solid structural six chemical drawn. red The onsuperscaffolds. are a targets. genes drugs with drug target known potential drug indicates 23 black potential of and The and drugs, to known known transformed different line. also of indicate dashed target, position vertical comparison haplotype. The the a a Fig.8 and by sharing subject indicated scaffolds the is between of furca- marker) nucleotide number The same (focal P the the haplotypes root to figure. showing shared The corresponds core the extended SNP lines of of 2002). the concept side al., of the right et thickness in the contained Sabeti on information C. displayed complete EHH(Pardis were the marker represent focal structures tion a around diversity around Nucleotide homozygosity line. haplotype horizontal dashed the above transporter shown were 1%) P top test (3.89, Z to (corresponding requirement regions selected the θ > ,ωιλδ(ΧΛΙ) π, ausadpotdi oaihi scale. logarithmic in plotted and values 0) 2 ako ua ooous 3 eae olta,L ret acd otdfc rsterile or defect molt flaccid, arrest, L3 lethal, to Related (3) homologues; human of Lack (2) 80%); lto H hwn oiudrpstv eeto fcpie(C ouain Nswith SNPs population. (SC) captive of selection positive under loci showing iHS of Plot .schroederi B. n in ad ee0.9 were panda giant and ced7 / (b) θ n ot epciey h 0 rycre of curves gray 100 The respectively. host, and ,ςαπτιvε(Σ῝) π, b) and ceai iga faaoia rs-eto of cross-section anatomical of diagram Schematic h egahcdsrbto ftesmln oain o L n Cpopulations. SC and QLI for locations sampling the of distribution geographic The ogtdnlcag fteeetv ouainsz fthe of size population effective the of change Longitudinal bre-4 .schroederi B. 1adL ersn nvtodvlpetlsae,adL aveetrtehost the enter larvae L2 and stages, developmental vitro in represent L2 and L1 . and ) Ne oiuig1-bsiigwnoswr ipae bv h ee.Tedcyof decay The genes. the above displayed were windows sliding 10-kb using loci Fst eeetmtduigteMM2mto.QI iln ouain SC: population; Qinling QLI: method. MSMC2 the using estimated were ) h e n upeln ersn h siae ffciepplto ieof size population effective estimated the represent line purple and red The (c) f5 bwnoswt 0k tp.Rddt ersn idw fulfilling windows represent dots Red steps. kb 10 with windows kb 50 of aiu ieiod(L hlgntcte ih10bosrptests bootstrap 100 with tree phylogenetic (ML) likelihood maximum A × .schroederi B. 10 n h ffc fatngn nmsl otato.(a) contraction. muscle on gene actin of effect the and -8 n . 10 x 1.3 and eosrce rmterfrneadpopulation and reference the from reconstructed 21 .schroederi B. -8 epciey h lc iesosteMRof MAR the shows line black The respectively. , < .schroederi B. .univale P. .0,where 0.005, .schroederi B. ouain itiuino nratio ln of Distribution population. steoutgroup; the as . Fst n otrpeettePSMC the represent host and .schroederi B. eoi ein ihselec- with regions Genomic eeaintm g of (g) time Generation > .1adl ratio ln and 0.21 ; (c) (c) PEHfo each from XP-EHH glc-1 utpesignaling Multiple ouain.The populations. ieetcolors Different (d) , | nrf-6 iHS Population μ | [?]iHS > of ) ABC , e 0.34). Life and (b) B. m Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. B. schroederi P. univalens C. elegans M. hapla c a A. suum

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process s T. canis ene l s ular proce * s sis tr C. elegans ansmi Contraction (vsM.hapla) Expansion (vsM.hapla) ** ** s s s M. hapla s i on Copy number 0 10 20 30 40 50 Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. c a V V V c a aline asopressin−regulated w aline Pro Carboh Metabolism ofx Amino sugarand Fc gammaR−mediatedphagocytosis ximal tub , leucineandisoleucinebiosynthesis

Rho family , leucineandisoleucinedegr P entose andglucuronateinterco ydr Steroid hor Cdc42 Dr ate digestionandabsor RhoA mRNA surveillancepathway Rac1 ule bicarbonatereclamation Ascorbate andalda ug metabolism−cytochromeP450 P Propanoate metabolism Regulation ofactincytos enobiotics Steroid ho AR signalingpathw Pyr n Ar Salmonella inf ucleotide sugarmetabolism mone biosynthesis achidonic acidmetabolism Miner uv ater reabsor Linoleic acidmetabolism Glutathione metabolism Oocyte meiosis ate metabolism L3 &L4 Galactose metabolism RNA tr VLM b al absor Spliceosome L3 Endocytosis r y cytochromeP450 mone biosynthesis Shigellosis Adherens junction r ate metabolism F Adults L5& anspor adation ocal adhesion Tight junction ection Phagosome ption ption ption Apoptosis n a v y t ersions k eleton 0 Proportion (target/background) -Log10(Pvalue) 10 0.12 N-WASP 1 Gene Count PAK L2 0.16 2 20 -Log10(Pvalue) Gene Count 0.20 L1 3 ROCK b Gene Number Phosphoenolp -Log10(P) 30 20 10 5 10 15 20 +p Ser ine−threonine/tyrosine−protein kinase d b T yr r anslation initiationf 24 uv ate carbo Arp2/3 MLCK semantic space x JNK1/MAPK8−associated membr UDP−glucuronosyl/UDP−glucosyltr −5 0 5 Nucleotide−diphospho−sugar tr −10 xykinase anatomical str Domain ofunkno actor regulation oflocomotion , GTP−utilising,conser Glycosyltr Heat shockprotein70f zinc c2h2typef My , betapropellor−lik ucture f Imm osin head,motordomain NAD(P)−binding domain unoglob Histone H2A/H2B/H3 or wn functionDUF148 mation in ansf Ribosomal protein −5 , catalyticdomain Actin Polymerization er +p +p ulin subtype2 ShKT domain NIDO domain ase f amily protein O v olv Actin f ane protein Histone H4 TU domain single−organism cellularprocess ansf ansf semantic spacey ed inmor e domain amily 92 Anne v response tobioticstim f eeding beha +p ed site er er cell comm amily amily ase ase xin phogenesis MLCP A. suum cellular componentbiogenesis MLC Actin unication vior 0

B. schroederi -p response tootherorganism localization ofcell ulus microtub

P. univalens se xual reproduction PSGs (P value) catabolic process cuticle ule−based process biosynthetic process 5 0.05 0.025 0

T. canis muscle epidermal intestine ovary oviduct uterus eggs Versatility Copy number low medium high Expansion Contraction 0 5 10 15 20 25 Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. A c a branch length=9.95

SICHUAN Effective population size (Ne; x10⁴) 10 15 20 0 5 10 4 SC (n=240) (outgroup) P. univale GANSU QLI Chengdu Years beforethepresent Tree scale:0.1 QLI (n=26) 100 100 Xi’an 10 5 SHAANXI SC Giant panda(host) B. schroederi 25 b d K=4 K=3 K=2 PCA2 (14.22%) -0.1 0.0 0.1 10 10

10 15 20 25 30 6 6 1.0 0.0 0.2 0.4 0.6 0.8 0.0 0.2 0.4 0.6 0.8 1.0 0.2 0.4 0.6 0.8 1.0

) years 1,000 ³/ (g/cm MAR B Effective population size 10 10 10 10 0.0 4 5 6 7 10 2 Years beforethepresent(B.schroederi) SC PCA1 (19.50%) QLI SC SC 0.1 QLI 10 3 0.2 QLI 10 4 Posted on Authorea 1 Jul 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162518309.92500415/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. b a 45679830. 45640260.0 43103608. 40474780. 39673316. 39603028. 38426488. 38011384. 37502912. 36639960. 35807804. 35557880. 35428200. 35370588. 35005740. 34201608. 31079718. 30533424. 21153306. 17833320. 16033398. 14005958. 11676326. 29236794. 26756106. 25768420. 21491572. 5701050. 3916670. 2105169. 1659693. 9736713. 7765001. 7322561. 5748580. 5520828. 5510710. 5371814. 4346851. 1835281. 1069073. 3809774. 2887666. 1997382. 514290. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 0 0 0 0 0 0 0 0 Density 0.6 0 0 0 -log(P) Fst 10 15 0 5 . . . 0 0 0 0 0 2 4 S 15 10 0 5 1 - S 4 4 1 S 9 ln ratio(θπ,wild(QLI)/θπ,captive(SC)) 1 B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B B a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a B B B B y y y y y y y ysch11393 ysch11314 y y ysch11212 y y y y y y y y y ysch10039 ysch10015 y y y y y y y y y ysch09137 y y y y y y y y 0.0 0.1 0.2 0.3 0.4 0.5 H a a a a s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s 3 C y y y y ch12076 (Piperazine) ch11869 ch11646 c ch12073 (Pyrvinium) ch11234 ch11201 ch11189 ch11148 ch10719 ch10378 ch10311 ch09750 ch08796 ch08540 ch08984 ch08948 ch08829 ch11574 ch11569 ch11440 ch11082 ch10777 ch10605 ch09626 ch08808 ch08730 ch08494 ch09492 ch09299 ch08810 ch19282 ch19115 ch19424 ch19163 s s s s h11463 ch13011( ch12834( ch12705( ch12920( glc-1 - ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (Iv ( ( ( ( ( ( (Iv ( ( ( ( (Iv ( ( ( ( ( ( ( ( ( ( 2 P P P P P P P P P P P P P P P M N M M N B O O O O O T T T T T T P P L T HO h h h h h h o o o o o o o o o y o o o y o u h i i e o o x x x x x P P H Pyr oxi e e e e e r r r r i i i i i i t t t t t t t t t t t t t pheni cant i i i i i i t t i bendazol i pacr r r r o o acet acet acet acet acet acet e abendazol b b b b b v v e e e e e e e e e e e e e dazol dazol e e Fst m m m xyl t t i i n n n n n n n n n n n n n endazol endazol endazol endazol endazol n n d e e a n n H ectin ectin ectin tia tia tia tia tia tia tia tia tia tia tia tia tia tia tia ectin 3 n n n i i C u u hone, r 1 i a a a a a a tia tia t n e e m m u l l l l l l l l l l l l l l l r r r r r r e e ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) H N N H e s sam sam sam sam sam sam l m l l , ) ) ) ) ) OH o , , , ) ) L ) M M M , r evam L e e e e e e c P oxi oxi oxi S , evam i i i i i i e ) ) ) ) ) i O r d d d d d d nol , azi P x ) ) ) ) ) ) dectin dectin dectin i y bendazol i ) quant s r i v 0 o s i l o n Epn-2 e H N l i , ) ) ) N NH e u B N e , m iHS S Pyr e l N ) pheni , N A O NH e a ) S l bendazol H CH H n 3 3 C 2 t O e N u CH tin-9.2 l CH m ) 10517769. 10489782. ASU_12729 3 8251208. 8229775. 3559876. 2085833. 3 9181572. 5591362. 3935072. 2515062. 1778907. ) 811933. 548499. 75350. O Fst ≥0.21 ln ratio e 2 ) 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 7678408. 7626316. 7563093. 6280917. 5224287. 4286296. 1899788. 343651. S S S 1 6 2 0 0 0 0 0 0 0 0 0 5907015. 4577958. 4183263. 4154164. 3911780. 2927089. 2148785. 1399939. ≥ 0.34 4 S B B B B B B B B B B B B B B 1 Ttbk1 a a a a a a a a a a a a a a 0 0 3 8 8 0 0 0 5 y y y y y y y ysch20623 ysch20555 y y y y y s s s s s s s s s s s s ch07130 ch07129 ch07000 ch06999 O S ch21300 ch20930 ch20752 ch20454 ch14812 ch14749 ch15028( ch14906( S 5 B B B B B B B B 4 2 a a a a a a a a dpy-5 HN O 0 CH y y y y ysch01691 y y y 0.06 0.08 0.10 0.12 3 s s s s s s s N ch01636 ch01311 ch01885 ch01880 ch01873 ch01760 ch01430 ( ( ( ( O P P P B B B B B B B B N 0 O 0 ( ( ( ( ( ( ( ( r r r L M x P P P P T T 6 P P a a a a a a a a azi azi azi RNF212B u CH i e h h y ysch02266( ysch02232( ysch02229( y y ysch02045( y N o o o o b o o H Scaffolds 0 0 1.0 1.5 cant 3 3 pacr s s s s i i endazol t t t t t t C quant quant quant CH acet acet . . e e e e e e ch01984( ch02382( ch02206( ch02117( 0 5 3 n n n n n n ced-7 tia tia tia tia tia tia ( ( ( ( ( ( ( ( O hone) H P A i P P P M P T 1 a a n O O h e e e y r r r r l l l l r l l 7 r r 0.5 e e ) ) ) ) O ) ) azi azi azi azi l l l t sam sam r i Cumulative e ) ) ) pacr e ) acet Density v ) H s O i quant quant quant quant n unat Fst P P P A T T T T Cumulative i CH O i i u h h h h o r r d d l i a bendazol 3 n azi azi 2 m i i i i t ) ) r H CH acet acet acet acet e e sam e 8 ) n 3 ) e e e e quant quant ) tia l l l l ) ) ) ) 1.0 a a a a O i 0.04 0.06 0.08 l d r r r r 11722122. 10978884. ) sam sam sam sam 9844499. 8255195. 7148374. 5981292. 5554014. 4544352. ) OH 900416. 3 e e e H 3 l l C 9 , ) ) P H 13355178. 12620896. 10031238. i i i i Fst 3 Cl 7457228. 6400256. 3137637. d d d d C y nrf-6 ) ) ) ) 0 0 5 0 0 0 0 0 0 r 5717916. 3683951. N v H GRE2 1.5 i 3 n C 6598952. 6542660. 6451809. 4 825003. 10 i c S 0 0 0 0 0 0 u m 7 0 3 N NH , T S 0 0 0 0 smc4 h S 3 i 1 B B B B B B B B B abendazol 11 S a a a a a a a a a 6 y y y y y y y y y 1 NH N O s s s s s s s s s -log(P) 10 -log(P) 10 1 B B B B B B ch16880 ch16816 ch16614 ch16507 ch16377 ch16330 ch16241 ch15934 ch16730 O CH a a a a a a 2 4 6 8 0 2 4 6 8 B B O 3 y y y y y y N a a 12 s s s s s s y y B B B B ch14686 ch13592 ch14081 ch13968 ch14350 ch14616 N s s a a a a e H ASU_14704 ch01078 ch00905 3 y y y y C Tcan_14228 ) 26 S s s s s S ten-1 glc-1 CH N ch05821 ch05828 ch05815 ch05256 ( ( ( ( ( ( ( ( ( N 3 13 P P P P P P P M L u o o y o o o o e O r cant t t t t t t bendazol N v e e e e e e ( ( ( ( ( ( P O P O O O i n n n n n n n 5293525. 5021856. 1314574. 1174989. nrf-6 ( ( CH N y r tia tia tia tia tia tia x x x x P H 14 i azi 3 NH hone, r u i i i i o CG9801 e b b b b v ( ( ( ( m l l l l l l xachl t M N P C ) ) ) ) ) ) i endazol endazol endazol endazol quant e Scaffolds n ) r H i y e n 3 i r azi 9 0 0 0 0 C u c t i tia e dazol 15 r P l m i o , Tcan_16034 H f O quant r o l onat s ) N 3 S azi ) C e XP-EHH r x por H ophene) l 2 i e e e e ) bendazol 16 O 3 CH quant e 1 1 C ) ) ) ) 3 ) e i 0.07 0.09 HLCS 0.08 0.10 0.1 e n ) 1 l e ) O O P ) 10932970. 10433511. 17 B B B B 3230013. 2282893. e a a a a pgp-3 l Fst ) y y y y Cl s s s s e 17 bre-4 18 ch02808( ch02511( ch02832( ch02500( ) OH 0 0 0 0 5571489. 4404993. 4397446. 4380768. 4379644. 4372343. 4341802. 4340932. 4333450. 3088513. HLCS Cl 7320703. 7292525. 5956342. 4540754. 3609840. 3496858. 3057457. 2416716. 19 7886509. 6103405. 4296010. 1354231. 1162682. Cl 957391. S 91556. 4 0 0 0 0 0 0 0 0 0 0 20 P P P C 0 0 0 0 0 0 0 0 o o r y 0 0 0 0 0 0 0 S ASU_07490 azi c t t ASU_03085 e e B B B B 1 l 21 o n n quant a a a a S 7 S s tia tia y y y y por 1 8 s s s s l l 2 ch04919 ch04175 ch04966 ch04099 ) ) B B B B B B B B B B i e n a a a a a a a a a a l e B B B B B B B B ) y y y y y y y y y y B B B B B B B ) s s s s s s s s s s a a a a a a a a a a a a a a a ch20230 ch20125 ch20124 ch20120 ch20118 ch20116 ch20109 ch20108 ch20107 ch20004 ysch22461 ysch22458 y y y y y y y y y y y y y s s s s s s s s s s s s s ch22202 ch22099 ch22067 ch22028 ch22330 ch22111 ( ( (Iv ( H O ch02967 ch02893 ch03769 ch03608 ch03323 ch03005 ch02985 P P N 3 H C 3 C o o i e r t t i r e e H dazol m 3 C n n H H ( ( ( ( ( ( ( ( ( ( ectin 3 tia tia C 3 C C N P P P P P P P P P o o o o o o o o o y ( ( ( ( ( ( ( ( CH N NH N O l l 5.510 ( ( ( ( ( ( ( M P P P O P T T e ) ) c t t t t t t t t t P P M M P M P 3 e e e e e e e e e ) l h h CH o o o r O x , e 380 o o o r r n n n n n n n n n azi M e e e i i t t t 3 i azi azi bendazol s acet acet O t t NH O tia tia tia tia tia tia tia tia tia H N b e e e bendazol bendazol bendazol e e oxi por H n n n endazol H 3 quant n n 3 C CH N O C quant quant l l l l l l l l l tia tia tia ) ) ) ) ) ) ) ) ) tia tia 3 O dectin CH Haplotype furcationsaround‘ced-7’ a a Haplotype furcationsaround‘glc-1’ i CH l l l n H O CH r r 3 H Haplotype furcationsaround‘bre-4’ l l ) ) ) 3 CH O C N H 3 sam sam ) ) 3 3 e 330 Haplotype furcationsaround‘nrf-6’ C 4.525 H 3 H HO ) e 3 S CH C N CH O 3 e e OH H O C l e 3 e l l ) 3 e e e H H OH ) ) , ) i i ) P , , , d d HN O O O O O H N O CH N y H ) ) 3 x x x O H H C CH r 3 3 3 H C C CH N H 3 O v i i i 3 C bendazol bendazol bendazol 5.515 O i 3 n Cl Cl i O N CH CH u O N H CH 3 3 m CH 385 3 N O 3 Cl O ) CH N 3 O e e e N NH CH ) ) ) CH 3 3 11567507. 11525025. 11096301. 12274551. 12266184. 11569648. 335 CH 4515156. 4513538. 4506591. 4501224. 4497000. 4493255. 3538850. 2735574. 2568028. 2505025. 1720674. 4.530 O NH 497899. 3 Positon (kb) Positon (Mb) Positon (Mb) Positon (kb) 1711828. 4347057. 4087008. 4053519. 4036236. 3412992. 2736662. 2735888. 2707305. 2700482. 2693657. 2677855. 2664044. 2636813. 2629251. 2621244. 6351343. 5436560. 4105540. 4087868. O 521906. CH 5743779. 4244900. 3164716. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 5.520 0 0 8 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 390 S S S 9 S 1 5 8 1 B B B B B B B B B B B B B B B B B B 3 a a a a a a a a a a a a a a a a a a B B y y y y y y y y y y y y y y y y y y 340 s s s s s s s s s s s s s s s s s s B B B B B B B B B B B B B B B B B B B a a 4.535 ch08346 ch08345 ch08281 ch08280 ch08270 ch08229 ch07654 ch07653 ch07651 ch07649 ch07648 ch07646 ch07553 ch07492 ch07481 ch07408 ch07326 ch07472 y y a a a a a a a a a a a a a a a a a a a B B B s s HO y y y y y y y y y y y y y y y y y y y O a a a ch18107 ch18298 s s s s s s s s s s s s s s s s s s s y y y ch00344 ch00339 ch00338 ch00334 ch00327 ch00271 ch00232 ch00231 ch00228 ch00223 ch00222 ch00221 ch00218 ch00217 ch00216 ch00215 ch00537 ch00444 ch00047 H s s s 3 OH CH C 3 ch17598 ch17392 ch17270 5.525 O O H O O H 3 C 3 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( C P P P P P P P P P P P P P P P P P H CH 395 O HO 3 o o o o o o o o o o o o o o o o o e ( ( O O P H O xachl t t t t t t t t t t t t t t t t t ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (Iv H e e e e e e e e e e e e e e e e e O 3 CH o P P P P P P P P P P P P P P P P O C e C O n n n n n n n n n n n n n n n n n 3 ( ( ( xachl t o o o o o o o o o o o o o o o o H y P H O x e 3 tia tia tia tia tia tia tia tia tia tia tia tia tia tia tia tia tia e C c t t t t t t t t t t t t t t t t CH i r o e n x b e e e e e e e e e e e e e e e e 3 CH m l o xachl t l l l l l l l l l l l l l l l l l i tia o n n n n n n n n n n n n n n n n 3 endazol ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) b e HO r Cl ectin s 345 tia tia tia tia tia tia tia tia tia tia tia tia tia tia tia tia HO n ophene) endazol o 4.540 l por H tia ) 3 C r O HO Cl l l l l l l l l l l l l l l l l ophene) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) o l i ) , n r M CH ophene) 3 O e e oxi H O HO 3 ) H Cl Cl C ) O 3 5.530 Cl e C ) O Cl H dectin 3 O OH CH C 400 3 O O O CH ) 3 O O H 3 C CH 3 CH 3