Virus-derived variation in diverse human genomes

English version

Autoři: Shohei Kojima ^aff001; Anselmo Jiro Kamada ^aff001; Nicholas F. Parrish ^aff001
Působiště autorů: Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan ^aff001
Vyšlo v časopise: Virus-derived variation in diverse human genomes. PLoS Genet 17(4): e1009324. doi:10.1371/journal.pgen.1009324
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009324

Souhrn

Acquisition of genetic material from viruses by their hosts can generate inter-host structural genome variation. We developed computational tools enabling us to study virus-derived structural variants (SVs) in population-scale whole genome sequencing (WGS) datasets and applied them to 3,332 humans. Although SVs had already been cataloged in these subjects, we found previously-overlooked virus-derived SVs. We detected non-germline SVs derived from squirrel monkey retrovirus (SMRV), human immunodeficiency virus 1 (HIV-1), and human T lymphotropic virus (HTLV-1); these variants are attributable to infection of the sequenced lymphoblastoid cell lines (LCLs) or their progenitor cells and may impact gene expression results and the biosafety of experiments using these cells. In addition, we detected new heritable SVs derived from human herpesvirus 6 (HHV-6) and human endogenous retrovirus-K (HERV-K). We report the first solo-direct repeat (DR) HHV-6 likely to reflect DR rearrangement of a known full-length endogenous HHV-6. We used linkage disequilibrium between single nucleotide variants (SNVs) and variants in reads that align to HERV-K, which often cannot be mapped uniquely using conventional short-read sequencing analysis methods, to locate previously-unknown polymorphic HERV-K loci. Some of these loci are tightly linked to trait-associated SNVs, some are in complex genome regions inaccessible by prior methods, and some contain novel HERV-K haplotypes likely derived from gene conversion from an unknown source or introgression. These tools and results broaden our perspective on the coevolution between viruses and humans, including ongoing virus-to-human gene transfer contributing to genetic variation between humans.

Klíčová slova:

Genome-wide association studies – Genomics – HTLV-1 – Human genomics – Mammalian genomics – Phylogenetic analysis – Polymerase chain reaction – Viral genomics

Zdroje

1. Prüfer K, de Filippo C, Grote S, Mafessoni F, Korlević P, Hajdinjak M, et al. A high-coverage Neandertal genome from Vindija Cave in Croatia. Science. 2017;358 : 655–658. doi: 10.1126/science.aao1887 28982794

2. Wildschutte JH, Williams ZH, Montesion M, Subramanian RP, Kidd JM, Coffin JM. Discovery of unfixed endogenous retrovirus insertions in diverse human populations. Proc Natl Acad Sci. 2016;113: E2326 LP–E2334. doi: 10.1073/pnas.1602336113 27001843

3. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409 : 860–921. doi: 10.1038/35057062 11237011

4. Li W, Lin L, Malhotra R, Yang L, Acharya R, Poss M. A computational framework to assess genome-wide distribution of polymorphic human endogenous retrovirus-K In human populations. PLoS Comput Biol. 2019;15: e1006564. doi: 10.1371/journal.pcbi.1006564 30921327

5. Macfarlane CM, Badge RM. Genome-wide amplification of proviral sequences reveals new polymorphic HERV-K(HML-2) proviruses in humans and chimpanzees that are absent from genome assemblies. Retrovirology. 2015;12 : 35. doi: 10.1186/s12977-015-0162-8 25927962

6. Thomas J, Perron H, Feschotte C. Variation in proviral content among human genomes mediated by LTR recombination. Mob DNA. 2018;9 : 36. doi: 10.1186/s13100-018-0142-3 30568734

7. Belshaw R, Dawson ALA, Woolven-Allen J, Redding J, Burt A, Tristem M. Genomewide screening reveals high levels of insertional polymorphism in the human endogenous retrovirus family HERV-K(HML2): implications for present-day activity. J Virol. 2005;79 : 12507–12514. doi: 10.1128/JVI.79.19.12507-12514.2005 16160178

8. Subramanian RP, Wildschutte JH, Russo C, Coffin JM. Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses. Retrovirology. 2011;8 : 90. doi: 10.1186/1742-4690-8-90 22067224

9. Bhardwaj N, Montesion M, Roy F, Coffin JM. Differential expression of HERV-K (HML-2) proviruses in cells and virions of the teratocarcinoma cell line Tera-1. Viruses. 2015;7 : 939–968. doi: 10.3390/v7030939 25746218

10. Horie M, Honda T, Suzuki Y, Kobayashi Y, Daito T, Oshida T, et al. Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature. 2010;463 : 84–7. doi: 10.1038/nature08695 20054395

11. Zhang E, Bell AJ, Wilkie GS, Suárez NM, Batini C, Veal CD, et al. Inherited Chromosomally Integrated Human Herpesvirus 6 Genomes Are Ancient, Intact, and Potentially Able To Reactivate from Telomeres. Sandri-Goldin RM, editor. J Virol. 2017;91. doi: 10.1128/JVI.01137-17 28835501

12. Liu X, Kosugi S, Koide R, Kawamura Y, Ito J, Miura H, et al. Endogenization and excision of human herpesvirus 6 in human genomes. PLoS Genet. 2020;16: e1008915. doi: 10.1371/journal.pgen.1008915 32776928

13. Aswad A, Aimola G, Wight D, Roychoudhury P, Zimmermann C, Hill J, et al. Evolutionary history of endogenous Human Herpesvirus 6 reflects human migration out of Africa. Mol Biol Evol. 2020. doi: 10.1093/molbev/msaa190 32722766

14. Weismann A. The germ-plasm: a theory of heredity. Scribner’s; 1893.

15. Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, et al. An integrated map of structural variation in 2,504 human genomes. Nature. 2015;526 : 75–81. doi: 10.1038/nature15394 26432246

16. Collins RL, Brand H, Karczewski KJ, Zhao X, Alföldi J, Francioli LC, et al. A structural variation reference for medical and population genetics. Nature. 2020;581 : 444–451. doi: 10.1038/s41586-020-2287-8 32461652

17. Almarri MA, Bergström A, Prado-Martinez J, Yang F, Fu B, Dunham AS, et al. Population Structure, Stratification, and Introgression of Human Structural Variation. Cell. 2020;182 : 189–199.e15. doi: 10.1016/j.cell.2020.05.024 32531199

18. Moustafa A, Xie C, Kirkness E, Biggs W, Wong E, Turpaz Y, et al. The blood DNA virome in 8,000 humans. PLoS Pathog. 2017;13: e1006292. doi: 10.1371/journal.ppat.1006292 28328962

19. Liu S, Huang S, Chen F, Zhao L, Yuan Y, Francis SS, et al. Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History. Cell. 2018;175 : 347–359.e14. doi: 10.1016/j.cell.2018.08.016 30290141

20. Bergström A, McCarthy SA, Hui R, Almarri MA, Ayub Q, Danecek P, et al. Insights into human genetic variation and population history from 929 diverse genomes. Science. 2020;367. doi: 10.1126/science.aay5012 32193295

21. Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526 : 68–74. doi: 10.1038/nature15393 26432245

22. Sun R, Grogan E, Shedd D, Bykovsky AF, Kushnaryov VM, Grossberg SE, et al. Transmissible retrovirus in Epstein-Barr virus-producer B95-8 cells. Virology. 1995;209 : 374–383. doi: 10.1006/viro.1995.1269 7778272

23. Cheval J, Muth E, Gonzalez G, Coulpier M, Beurdeley P, Cruveiller S, et al. Adventitious Virus Detection in Cells by High-Throughput Sequencing of Newly Synthesized RNAs: Unambiguous Differentiation of Cell Infection from Carryover of Viral Nucleic Acids. mSphere. 2019;4. doi: 10.1128/mSphere.00298-19 31167947

24. Rhim JS, Schell K, Creasy B, Case W. Biological characteristics and viral susceptibility of an African green monkey kidney cell line (Vero). Proc Soc Exp Biol Med Soc Exp Biol Med (New York, NY). 1969;132 : 670–678. doi: 10.3181/00379727-132-34285 4982209

25. Feusier J, Watkins WS, Thomas J, Farrell A, Witherspoon DJ, Baird L, et al. Pedigree-based estimation of human mobile element retrotransposition rates. Genome Res. 2019;29 : 1567–1577. doi: 10.1101/gr.247965.118 31575651

26. Sasani TA, Pedersen BS, Gao Z, Baird L, Przeworski M, Jorde LB, et al. Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation. Elife. 2019;8. doi: 10.7554/eLife.46922 31549960

27. Oda T, Ikeda S, Watanabe S, Hatsushika M, Akiyama K, Mitsunobu F. Molecular cloning, complete nucleotide sequence, and gene structure of the provirus genome of a retrovirus produced in a human lymphoblastoid cell line. Virology. 1988;167 : 468–476. 3201749

28. Lappalainen T, Sammeth M, Friedländer MR, ‘ t Hoen PAC, Monlong J, Rivas MA, et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature. 2013;501 : 506–511. doi: 10.1038/nature12531 24037378

29. Tan K-T, Ding L-W, Sun Q-Y, Lao Z-T, Chien W, Ren X, et al. Profiling the B/T cell receptor repertoire of lymphocyte derived cell lines. BMC Cancer. 2018;18 : 940. doi: 10.1186/s12885-018-4840-5 30285677

30. Sebastian NT, Zaikos TD, Terry V, Taschuk F, McNamara LA, Onafuwa-Nuga A, et al. CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo. PLoS Pathog. 2017;13: e1006509. doi: 10.1371/journal.ppat.1006509 28732051

31. McHugh D, Myburgh R, Caduff N, Spohn M, Kok YL, Keller CW, et al. EBV renders B cells susceptible to HIV-1 in humanized mice. Life Sci alliance. 2020;3. doi: 10.26508/lsa.202000640 32576602

32. Telford M, Navarro A, Santpere G. Whole genome diversity of inherited chromosomally integrated HHV-6 derived from healthy individuals of diverse geographic origin. Sci Rep. 2018;8 : 3472. doi: 10.1038/s41598-018-21645-x 29472617

33. Martens UM, Zijlmans JM, Poon SS, Dragowska W, Yui J, Chavez EA, et al. Short telomeres on human chromosome 17p. Nat Genet. 1998;18 : 76–80. doi: 10.1038/ng0198-018 9425906

34. Payer LM, Steranka JP, Yang WR, Kryatova M, Medabalimi S, Ardeljan D, et al. Structural variants caused by Alu insertions are associated with risks for many human diseases. Proc Natl Acad Sci U S A. 2017;114: E3984–E3992. doi: 10.1073/pnas.1704117114 28465436

35. Wallace AD, Wendt GA, Barcellos LF, de Smith AJ, Walsh KM, Metayer C, et al. To ERV Is Human: A Phenotype-Wide Scan Linking Polymorphic Human Endogenous Retrovirus-K Insertions to Complex Phenotypes. Front Genet. 2018;9 : 298. doi: 10.3389/fgene.2018.00298 30154825

36. Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 2019;47: D1005–D1012. doi: 10.1093/nar/gky1120 30445434

37. Audano PA, Sulovari A, Graves-Lindsay TA, Cantsilieris S, Sorensen M, Welch AE, et al. Characterizing the Major Structural Variant Alleles of the Human Genome. Cell. 2019;176 : 663–675.e19. doi: 10.1016/j.cell.2018.12.019 30661756

38. De Coster W, Van Broeckhoven C. Newest Methods for Detecting Structural Variations. Trends Biotechnol. 2019;37 : 973–982. doi: 10.1016/j.tibtech.2019.02.003 30902345

39. Linardopoulou E V, Williams EM, Fan Y, Friedman C, Young JM, Trask BJ. Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication. Nature. 2005;437 : 94–100. doi: 10.1038/nature04029 16136133

40. Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, et al. Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nat Commun. 2019;10 : 1784. doi: 10.1038/s41467-018-08148-z 30992455

41. Scally A, Durbin R. Revising the human mutation rate: implications for understanding human evolution. Nature reviews. Genetics. England; 2012. pp. 745–753. doi: 10.1038/nrg3295 22965354

42. Hughes JF, Coffin JM. Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome. Genetics. 2005;171 : 1183–1194. doi: 10.1534/genetics.105.043976 16157677

43. Volleth M, Zenker M, Joksic I, Liehr T. Long-term Culture of EBV-induced Human Lymphoblastoid Cell Lines Reveals Chromosomal Instability. J Histochem Cytochem Off J Histochem Soc. 2020;68 : 239–251. doi: 10.1369/0022155420910113 32108534

44. Nanbo A, Inoue K, Adachi-Takasawa K, Takada K. Epstein-Barr virus RNA confers resistance to interferon-alpha-induced apoptosis in Burkitt’s lymphoma. EMBO J. 2002;21 : 954–965. doi: 10.1093/emboj/21.5.954 11867523

45. Furuta R, Yasunaga J-I, Miura M, Sugata K, Saito A, Akari H, et al. Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo. PLoS Pathog. 2017;13: e1006722. doi: 10.1371/journal.ppat.1006722 29186194

46. Mahé D, Matusali G, Deleage C, Alvarenga RLLS, Satie A-P, Pagliuzza A, et al. Potential for virus endogenization in humans through testicular germ cell infection: the case of HIV. bioRxiv. 2020; 2020.06.04.135657. doi: 10.1101/2020.06.04.135657

47. Stoye JP. Koala retrovirus: a genome invasion in real time. Genome Biol. 2006;7 : 241. doi: 10.1186/gb-2006-7-11-241 17118218

48. Gaccioli F, Lager S, de Goffau MC, Sovio U, Dopierala J, Gong S, et al. Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia. Nat Microbiol. 2020. doi: 10.1038/s41564-020-0711-3 32367053

49. Gravel A, Dubuc I, Morissette G, Sedlak RH, Jerome KR, Flamand L. Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris. Proc Natl Acad Sci. 2015;112 : 8058 LP –⁠ 8063. doi: 10.1073/pnas.1502741112 26080419

50. Ewing AD, Smits N, Sanchez-Luque FJ, Faivre J, Brennan PM, Richardson SR, et al. Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling. Mol Cell. 2020. doi: 10.1016/j.molcel.2020.10.024 33186547

51. Zhou W, Emery SB, Flasch DA, Wang Y, Kwan KY, Kidd JM, et al. Identification and characterization of occult human-specific LINE-1 insertions using long-read sequencing technology. Nucleic Acids Res. 2020;48 : 1146–1163. doi: 10.1093/nar/gkz1173 31853540

52. Zhou W, Nielsen JB, Fritsche LG, Dey R, Gabrielsen ME, Wolford BN, et al. Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. Nat Genet. 2018;50 : 1335–1341. doi: 10.1038/s41588-018-0184-y 30104761

53. Jha AR, Pillai SK, York VA, Sharp ER, Storm EC, Wachter DJ, et al. Cross-sectional dating of novel haplotypes of HERV-K 113 and HERV-K 115 indicate these proviruses originated in Africa before Homo sapiens. Mol Biol Evol. 2009;26 : 2617–2626. doi: 10.1093/molbev/msp180 19666991

54. Turner G, Barbulescu M, Su M, Jensen-Seaman MI, Kidd KK, Lenz J. Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr Biol. 2001;11 : 1531–1535. doi: 10.1016/s0960-9822(01)00455-9 11591322

55. Dewannieux M, Harper F, Richaud A, Letzelter C, Ribet D, Pierron G, et al. Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res. 2006;16 : 1548–1556. doi: 10.1101/gr.5565706 17077319

56. Green ED, Gunter C, Biesecker LG, Di Francesco V, Easter CL, Feingold EA, et al. Strategic vision for improving human health at The Forefront of Genomics. Nature. 2020;586 : 683–692. doi: 10.1038/s41586-020-2817-4 33116284

57. Kumata R, Ito J, Takahashi K, Suzuki T, Sato K. A tissue level atlas of the healthy human virome. BMC Biol. 2020;18 : 55. doi: 10.1186/s12915-020-00785-5 32493363

Článek Analysis of cell-type-specific chromatin modifications and gene expression in Drosophila neurons that direct reproductive behavior

Článek Aurora kinase A is essential for meiosis in mouse oocytes

Článek Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults

Článek An insulator blocks access to enhancers by an illegitimate promoter, preventing repression by transcriptional interference

Článek Coordinating the morphogenesis-differentiation balance by tweaking the cytokinin-gibberellin equilibrium

Článek Leveraging expression from multiple tissues using sparse canonical correlation analysis and aggregate tests improves the power of transcriptome-wide association studies

Článek Functional assessment of the “two-hit” model for neurodevelopmental defects in Drosophila and X. laevis

Článek ARID1A regulates R-loop associated DNA replication stress

Článek Ubiquitin-protein ligase Ubr5 cooperates with hedgehog signalling to promote skeletal tissue homeostasis

Článek Pathways and signatures of mutagenesis at targeted DNA nicks

Článek LuxT controls specific quorum-sensing-regulated behaviors in Vibrionaceae spp. via repression of qrr1, encoding a small regulatory RNA

Článek A complex genetic architecture in zebrafish relatives Danio quagga and D. kyathit underlies development of stripes and spots