Volume 43 Issue 3
May  2022
Turn off MathJax
Article Contents
Jia-Qi Chen, Ming-Peng Zhang, Xin-Kai Tong, Jing-Quan Li, Zhou Zhang, Fei Huang, Hui-Peng Du, Meng Zhou, Hua-Shui Ai, Lu-Sheng Huang. Scan of the endogenous retrovirus sequences across the swine genome and survey of their copy number variation and sequence diversity among various Chinese and Western pig breeds. Zoological Research, 2022, 43(3): 423-441. doi: 10.24272/j.issn.2095-8137.2021.379
Citation: Jia-Qi Chen, Ming-Peng Zhang, Xin-Kai Tong, Jing-Quan Li, Zhou Zhang, Fei Huang, Hui-Peng Du, Meng Zhou, Hua-Shui Ai, Lu-Sheng Huang. Scan of the endogenous retrovirus sequences across the swine genome and survey of their copy number variation and sequence diversity among various Chinese and Western pig breeds. Zoological Research, 2022, 43(3): 423-441. doi: 10.24272/j.issn.2095-8137.2021.379

Scan of the endogenous retrovirus sequences across the swine genome and survey of their copy number variation and sequence diversity among various Chinese and Western pig breeds

doi: 10.24272/j.issn.2095-8137.2021.379
Funds:  This study was supported by the National Swine Industry and Technology System of China (nycytx-009), and National Natural Science Foundation of China (31672383)
More Information
  • In pig-to-human xenotransplantation, the transmission risk of porcine endogenous retroviruses (PERVs) is of great concern. However, the distribution of PERVs in pig genomes, their genetic variation among Eurasian pigs, and their evolutionary history remain unclear. We scanned PERVs in the current pig reference genome (assembly Build 11.1), and identified 36 long complete or near-complete PERVs (lcPERVs) and 23 short incomplete PERVs (siPERVs). Besides three known PERVs (PERV-A, -B, and -C), four novel types (PERV-JX1, -JX2, -JX3, and -JX4) were detected in this study. According to evolutionary analyses, the newly discovered PERVs were more ancient, and PERV-Bs probably experienced a bottleneck ~0.5 million years ago (Ma). By analyzing 63 high-quality porcine whole-genome resequencing data, we found that the PERV copy numbers in Chinese pigs were lower (32.0±4.0) than in Western pigs (49.1±6.5). Additionally, the PERV sequence diversity was lower in Chinese pigs than in Western pigs. Regarding the lcPERV copy numbers, PERV-A and -JX2 in Western pigs were higher than in Chinese pigs. Notably, Bama Xiang (BMX) pigs had the lowest PERV copy number (27.8±5.1), and a BMX individual had no PERV-C and the lowest PERV copy number (23), suggesting that BMX pigs were more suitable for screening and/or modification as xenograft donors. Furthermore, we identified 451 PERV transposon insertion polymorphisms (TIPs), of which 86 were shared by all 10 Chinese and Western pig breeds. Our findings provide systematic insights into the genomic distribution, variation, evolution, and possible biological function of PERVs.
  • loading
  • [1]
    Ai HS, Fang XD, Yang B, Huang ZY, Chen H, Mao LK, et al. 2015. Adaptation and possible ancient interspecies introgression in pigs identified by whole-genome sequencing. Nature Genetics, 47(3): 217−225. doi: 10.1038/ng.3199
    Ai HS, Zhang MP, Yang B, Goldberg A, Li WB, Ma JW, et al. 2021. Human-mediated admixture and selection shape the diversity on the modern swine (Sus scrofa) Y chromosomes. Molecular Biology and Evolution, 38(11): 5051−5065. doi: 10.1093/molbev/msab230
    Bartosch B, Stefanidis D, Myers R, Weiss R, Patience C, Takeuchi Y. 2004. Evidence and consequence of porcine endogenous retrovirus recombination. Journal of Virology, 78(24): 13880−13890. doi: 10.1128/JVI.78.24.13880-13890.2004
    Bartosch B, Weiss RA, Takeuchi Y. 2002. PCR-based cloning and immunocytological titration of infectious porcine endogenous retrovirus subgroup A and B. Journal of General Virology, 83(9): 2231−2240. doi: 10.1099/0022-1317-83-9-2231
    Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. 2009. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics, 25(8): 1091−1093. doi: 10.1093/bioinformatics/btp101
    Carpentier MC, Manfroi E, Wei FJ, Wu HP, Lasserre E, Llauro C, et al. 2019. Retrotranspositional landscape of Asian rice revealed by 3000 genomes. Nature Communication, 10(1): 24. doi: 10.1038/s41467-018-07974-5
    Chen H, Huang M, Yang B, Wu ZP, Deng Z, Hou Y, et al. 2020a. Introgression of Eastern Chinese and Southern Chinese haplotypes contributes to the improvement of fertility and immunity in European modern pigs. Gigascience, 9(3): giaa014. doi: 10.1093/gigascience/giaa014
    Chen N. 2004. Using RepeatMasker to identify repetitive elements in genomic sequences. Current Protocols in Bioinformatics, 5(1): 4.10.1−4.10.14.
    Chen YC, Chen MY, Duan XY, Cui J. 2020b. Ancient origin and complex evolution of porcine endogenous retroviruses. Biosafety and Health, 2(3): 142−151. doi: 10.1016/j.bsheal.2020.03.003
    Cohen CJ, Lock WM, Mager DL. 2009. Endogenous retroviral LTRs as promoters for human genes: a critical assessment. Gene, 448(2): 105−114. doi: 10.1016/j.gene.2009.06.020
    Cooper DKC. 2003. Clinical xenotransplantion—how close are we?. The Lancet, 362(9383): 557−559. doi: 10.1016/S0140-6736(03)14118-9
    Denner J. 2008. Recombinant porcine endogenous retroviruses (PERV-A/C): a new risk for xenotransplantation?. Archives of Virology, 153(8): 1421−1426. doi: 10.1007/s00705-008-0141-7
    Denner J. 2016a. Expression and function of endogenous retroviruses in the placenta. APMIS, 124(1-2): 31−43. doi: 10.1111/apm.12474
    Denner J. 2016b. How active are porcine endogenous retroviruses (PERVs)?. Viruses, 8(8): 215. doi: 10.3390/v8080215
    Denner J. 2018. Why was PERV not transmitted during preclinical and clinical xenotransplantation trials and after inoculation of animals?. Retrovirology, 15(1): 28. doi: 10.1186/s12977-018-0411-8
    Denner J, Tönjes RR. 2012. Infection barriers to successful xenotransplantation focusing on porcine endogenous retroviruses. Clinical Microbiology Reviews, 25(2): 318−343. doi: 10.1128/CMR.05011-11
    Deorowicz S, Kokot M, Grabowski S, Debudaj-Grabysz A. 2015. KMC 2: fast and resource-frugal k-mer counting. Bioinformatics, 31(10): 1569−1576. doi: 10.1093/bioinformatics/btv022
    Drummond AJ, Rambaut A. 2007. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evolutionary Biology, 7(1): 214. doi: 10.1186/1471-2148-7-214
    Fan X, Abbott TE, Larson D, Chen K. 2014. BreakDancer: identification of genomic structural variation from paired-end read mapping. Current Protocols in Bioinformatics, 45: 15.6.1−11.
    Fiebig U, Fischer K, Bähr A, Runge C, Schnieke A, Wolf E, et al. 2018. Porcine endogenous retroviruses: Quantification of the copy number in cell lines, pig breeds, and organs. Xenotransplantation, 25(4): e12445. doi: 10.1111/xen.12445
    Frantz LAF, Schraiber JG, Madsen O, Megens HJ, Bosse M, Paudel Y, et al. 2013. Genome sequencing reveals fine scale diversification and reticulation history during speciation in Sus. Genome Biology, 14(9): R107.
    Frantz LAF, Schraiber JG, Madsen O, Megens HJ, Cagan A, Bosse M, et al. 2015. Evidence of long-term gene flow and selection during domestication from analyses of Eurasian wild and domestic pig genomes. Nature Genetics, 47(10): 1141−1148. doi: 10.1038/ng.3394
    Garkavenko O, Wynyard S, Nathu D, Muzina M, Muzina Z, Scobie L, et al. 2008. Porcine endogenous retrovirus transmission characteristics from a designated pathogen-free herd. Transplantation Proceedings, 40(2): 590−593. doi: 10.1016/j.transproceed.2008.01.051
    Gel B, Serra E. 2017. karyoploteR: an R/Bioconductor package to plot customizable genomes displaying arbitrary data. Bioinformatics, 33(19): 3088−3090. doi: 10.1093/bioinformatics/btx346
    Grandbastien MA. 1998. Activation of plant retrotransposons under stress conditions. Trends in Plant Science, 3(5): 181−187. doi: 10.1016/S1360-1385(98)01232-1
    Groenen MAM. 2016. A decade of pig genome sequencing: a window on pig domestication and evolution. Genetics Selection Evolution, 48(1): 23. doi: 10.1186/s12711-016-0204-2
    Groenen MAM, Archibald AL, Uenishi H, Tuggle CK, Takeuchi Y, Rothschild MF, et al. 2012. Analyses of pig genomes provide insight into porcine demography and evolution. Nature, 491(7424): 393−398. doi: 10.1038/nature11622
    Harrison I, Takeuchi Y, Bartosch B, Stoye JP. 2004. Determinants of high titer in recombinant porcine endogenous retroviruses. Journal of Virology, 78(24): 13871−13879. doi: 10.1128/JVI.78.24.13871-13879.2004
    Hénaff E, Zapata L, Casacuberta JM, Ossowski S. 2015. Jitterbug: somatic and germline transposon insertion detection at single-nucleotide resolution. BMC Genomics, 16(1): 768. doi: 10.1186/s12864-015-1975-5
    Kabát P, Tristem M, Opavský R, Pastorek J. 1996. Human endogenous retrovirus HC2 is a new member of the S71 retroviral subgroup with a full-length pol gene. Virology, 226(1): 83−94. doi: 10.1006/viro.1996.0630
    Karlas A, Irgang M, Votteler J, Specke V, Özel M, Kurth R, et al. 2010. Characterisation of a human cell-adapted porcine endogenous retrovirus PERV-A/C. Annals of Transplantation, 15(2): 45−54.
    Katoh K, Standley DM. 2013. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Molecular Biology and Evolution, 30(4): 772−780. doi: 10.1093/molbev/mst010
    Kent WJ. 2002. BLAT-the BLAST-like alignment tool. Genome Research, 12(4): 656−664.
    Kozak CA. 1984. Differential expression of murine leukemia virus loci in chemically induced hybrid cells. Journal of Virology, 51(3): 876−879. doi: 10.1128/jvi.51.3.876-879.1984
    Krüger L, Kristiansen Y, Reuber E, Möller L, Laue M, Reimer C, et al. 2019. A comprehensive strategy for screening for xenotransplantation-relevant viruses in a second isolated population of Göttingen minipigs. Viruses, 12(1): 38. doi: 10.3390/v12010038
    Krüger L, Stillfried M, Prinz C, Schroder V, Neubert LK, Denner J. 2020. Copy number and prevalence of porcine endogenous retroviruses (PERVs) in German Wild Boars. Viruses, 12(4): 419. doi: 10.3390/v12040419
    Kumar S, Stecher G, Li M, Knyaz C, Tamura K. 2018. MEGA X: molecular evolutionary genetics analysis across computing platforms. Molecular Biology and Evolution, 35(6): 1547−1549. doi: 10.1093/molbev/msy096
    Kumar S, Stecher G, Suleski M, Hedges SB. 2017. TimeTree: a resource for timelines, timetrees, and divergence times. Molecular Biology and Evolution, 34(7): 1812−1819. doi: 10.1093/molbev/msx116
    Kunarso G, Chia NY, Jeyakani J, Hwang C, Lu XY, Chan YS, et al. 2010. Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nature Genetics, 42(7): 631−634. doi: 10.1038/ng.600
    Lanciano S, Cristofari G. 2020. Measuring and interpreting transposable element expression. Nature Reviews Genetics, 21(12): 721−736. doi: 10.1038/s41576-020-0251-y
    Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with Bowtie 2. Nature Methods, 9(4): 357−359. doi: 10.1038/nmeth.1923
    Larson G, Dobney K, Albarella U, Fang MY, Matisoo-Smith E, Robins J, et al. 2005. Worldwide phylogeography of wild boar reveals multiple centers of pig domestication. Science, 307(5715): 1618−1621. doi: 10.1126/science.1106927
    Le Tissier P, Stoye JP, Takeuchi Y, Patience C, Weiss RA. 1997. Two sets of human-tropic pig retrovirus. Nature, 389(6652): 681−682. doi: 10.1038/39489
    Lee D, Lee J, Yoon JK, Kim NY, Kim GW, Park C, et al. 2011. Rapid determination of perv copy number from porcine genomic DNA by real-time polymerase chain reaction. Animal Biotechnology, 22(4): 175−180. doi: 10.1080/10495398.2011.595294
    Lee JH, Webb GC, Allen RDM, Moran C. 2002. Characterizing and mapping porcine endogenous retroviruses in Westran pigs. Journal of Virology, 76(11): 5548−5556. doi: 10.1128/JVI.76.11.5548-5556.2002
    Letunic I, Bork P. 2019. Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Research, 47(W1): W256−W259. doi: 10.1093/nar/gkz239
    Li H, Durbin R. 2009. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics, 25(14): 1754−1760. doi: 10.1093/bioinformatics/btp324
    Lian ZX, Rogel-Gaillard C, Li N, Chardon P, Wu CX. 2002. Copy number polymorphism of endogenous retrovirus sequence in Chinese local pig breeds by Semi-PCR. Acta Veterinaria et Zootechnica Sinica, 33(6): 521−524.
    Liu G, Li Z, Pan M, Ge M, Wang Y, Gao Y. 2011. Genetic prevalence of porcine endogenous retrovirus in Chinese experimental miniature pigs. Transplantation Proceedings, 43(7): 2762−2769. doi: 10.1016/j.transproceed.2011.06.061
    Mang R, Maas J, Chen XH, Goudsmit J, Van Der Kuyl AC. 2001. Identification of a novel type C porcine endogenous retrovirus: evidence that copy number of endogenous retroviruses increases during host inbreeding. Journal of General Virology, 82(8): 1829−1834. doi: 10.1099/0022-1317-82-8-1829
    Matos MC, Pinheiro A, Melo-Ferreira J, Davis RS, Esteves PJ. 2021. Evolution of Fc receptor-like scavenger in mammals. Frontiers in Immunology, 11: 590280. doi: 10.3389/fimmu.2020.590280
    Morales JF, Snow ET, Murnane JP. 2003. Environmental factors affecting transcription of the human L1 retrotransposon. II. Stressors. Mutagenesis, 18(2): 151−158. doi: 10.1093/mutage/18.2.151
    Morgulis A, Coulouris G, Raytselis Y, Madden TL, Agarwala R, Schäffer AA. 2008. Database indexing for production MegaBLAST searches. Bioinformatics, 24(16): 1757−1764. doi: 10.1093/bioinformatics/btn322
    Niebert M, Tönjes RR. 2005. Evolutionary spread and recombination of porcine endogenous retroviruses in the Suiformes. Journal of Virology, 79(1): 649–654.
    Niu D, Wei HJ, Lin L, George H, Wang T, Lee IH, et al. 2017. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science, 357(6357): 1303−1307. doi: 10.1126/science.aan4187
    Patience C, Switzer WM, Takeuchi Y, Griffiths DJ, Goward ME, Heneine W, et al. 2001. Multiple groups of novel retroviral genomes in pigs and related species. Journal of Virology, 75(6): 2771−2775. doi: 10.1128/JVI.75.6.2771-2775.2001
    Patience C, Takeuchi Y, Weiss RA. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nature Medicine, 3(3): 282−286. doi: 10.1038/nm0397-282
    Premachandra HKA, La Cruz FLD, Takeuchi Y, Miller A, Fielder S, O’Connor W, et al. 2017. Genomic DNA variation confirmed Seriola lalandi comprises three different populations in the Pacific, but with recent divergence. Scientific Reports, 7(1): 9386. doi: 10.1038/s41598-017-07419-x
    Quereda JJ, Herrero-Medrano JM, Abellaneda JM, García-Nicolás O, Martínez-Alarcón L, Pallarés FJ, et al. 2012. Porcine endogenous retrovirus copy number in different pig breeds is not related to genetic diversity. Zoonoses and Public Health, 59(6): 401−407. doi: 10.1111/j.1863-2378.2012.01467.x
    Quinlan AR, Hall IM. 2010. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics, 26(6): 841−842. doi: 10.1093/bioinformatics/btq033
    Rombel IT, Sykes KF, Rayner S, Johnston SA. 2002. ORF-FINDER: a vector for high-throughput gene identification. Gene, 282(1-2): 33−41. doi: 10.1016/S0378-1119(01)00819-8
    Scheef G, Fischer N, Krach U, Tönjes RR. 2001. The number of a U3 repeat box acting as an enhancer in long terminal repeats of polytropic replication-competent porcine endogenous retroviruses dynamically fluctuates during serial virus passages in human cells. Journal of Virology, 75(15): 6933−6940. doi: 10.1128/JVI.75.15.6933-6940.2001
    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11): 2498−2504. doi: 10.1101/gr.1239303
    Sykes M, Sachs DH. 2019. Transplanting organs from pigs to humans. Science Immunology, 4(41): eaau6298. doi: 10.1126/sciimmunol.aau6298
    Sypniewski D, Machnik G, Mazurek U, Wilczok T, Smorag Z, Jura J, et al. 2005. Distribution of porcine endogenous retroviruses (PERVs) DNA in organs of a domestic pig. Annals of Transplantation, 10(2): 46−51.
    Tönjes RR, Niebert M. 2003. Relative age of proviral porcine endogenous retrovirus sequences in Sus scrofa based on the molecular clock hypothesis. Journal of Virology, 77(22): 12363−12368. doi: 10.1128/JVI.77.22.12363-12368.2003
    Wang T, Zeng J, Lowe CB, Sellers RG, Salama SR, Yang M, et al. 2007. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proceedings of the National Academy of Sciences of the United States of America, 104(47): 18613−18618. doi: 10.1073/pnas.0703637104
    Warr A, Affara N, Aken B, Beiki H, Bickhart DM, Billis K, et al. 2020. An improved pig reference genome sequence to enable pig genetics and genomics research. Gigascience, 9(6): giaa051. doi: 10.1093/gigascience/giaa051
    Wilson CA, Wong S, VanBrocklin M, Federspiel MJ. 2000. Extended analysis of the in vitro tropism of porcine endogenous retrovirus. Journal of Virology, 74(1): 49−56. doi: 10.1128/JVI.74.1.49-56.2000
    Yan GR, Guo TF, Xiao SJ, Zhang F, Xin WS, Huang T, et al. 2018. Imputation-based whole-genome sequence association study reveals constant and novel loci for hematological traits in a large-scale swine F2 resource population. Frontiers in Genetics, 9: 401. doi: 10.3389/fgene.2018.00401
    Yang B, Cui LL, Perez-Enciso M, Traspov A, Crooijmans RPMA, Zinovieva N, Schook LB, et al. 2017. Genome-wide SNP data unveils the globalization of domesticated pigs. Genetics Selection Evolution, 49(1): 71. doi: 10.1186/s12711-017-0345-y
    Yang LH, Güell M, Niu D, George H, Lesha E, Grishin D, et al. 2015. Genome-wide inactivation of porcine endogenous retroviruses (PERVs). Science, 350(6264): 1101−1104. doi: 10.1126/science.aad1191
    Yang YG, Sykes M. 2007. Xenotransplantation: current status and a perspective on the future. Nature Reviews Immunology, 7(7): 519−531. doi: 10.1038/nri2099
    Yoon JK, Choi J, Lee HJ, Cho Y, Gwon YD, Jang Y, et al. 2015. Distribution of porcine endogenous retrovirus in different organs of the hybrid of a Landrace and a Jeju domestic pig in Korea. Transplantation Proceedings, 47(6): 2067−2071. doi: 10.1016/j.transproceed.2015.05.023
    Yue YN, Xu WD, Kan YN, Zhao HY, Zhou YX, Song XB, et al. 2021. Extensive germline genome engineering in pigs. Nature Biomedical Engineering, 5(2): 134−143. doi: 10.1038/s41551-020-00613-9
    Zhang L, Huang YM, Si JL, Wu YJ, Wang M, Jiang QY, et al. 2018. Comprehensive inbred variation discovery in Bama pigs using de novo assemblies. Gene, 679: 81−89. doi: 10.1016/j.gene.2018.08.051
    Zhang P, Yu P, Wang W, Zhang L, Li SF, Bu H. 2010. An effective method for the quantitative detection of porcine endogenous retrovirus in pig tissues. In Vitro Cellular & Developmental Biology - Animal volume, 46(5): 408−410.
  • ZR-2021-379 Supplementary Materials.zip
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(2)

    Article Metrics

    Article views (1547) PDF downloads(184) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint