Review

Endogenous viruses: insights into viral evolution and impact on host biology

  • Nature Reviews Genetics volume 13, pages 283296 (2012)
  • doi:10.1038/nrg3199
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Abstract

Recent studies have uncovered myriad viral sequences that are integrated or 'endogenized' in the genomes of various eukaryotes. Surprisingly, it appears that not just retroviruses but almost all types of viruses can become endogenous. We review how these genomic 'fossils' offer fresh insights into the origin, evolutionary dynamics and structural evolution of viruses, which are giving rise to the burgeoning field of palaeovirology. We also examine the multitude of ways through which endogenous viruses have influenced, for better or worse, the biology of their hosts. We argue that the conflict between hosts and viruses has led to the invention and diversification of molecular arsenals, which, in turn, promote the cellular co-option of endogenous viruses.

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References

  1. 1.

    & Here a virus, there a virus, everywhere the same virus? Trends Microbiol. 13, 278–284 (2005).

  2. 2.

    , & The ancient Virus World and evolution of cells. Biol. Direct 1, 29 (2006).

  3. 3.

    & The origin of viruses. Res. Microbiol. 160, 466–472 (2009).

  4. 4.

    & Endogenous viral elements in animal genomes. PLoS Genet. 6, e1001191 (2010). This paper presents a systematic in silico mining of EVEs in animal genomes (that were available at the time), revealing that all major types of eukaryotic viruses can be endogenized.

  5. 5.

    , & Paleovirology — ghosts and gifts of viruses past. Curr. Opin. Virol. 1, 304–309 (2011).

  6. 6.

    & Perspective: transposable elements, parasitic DNA, and genome evolution. Evolution 55, 1–24 (2001).

  7. 7.

    & Dynamic interactions between transposable elements and their hosts. Nature Rev. Genet. 12, 615–627 (2011).

  8. 8.

    , , & A four-partner plant–virus interaction: enemies can also come from within. Mol. Plant Microbe Interact. 23, 1394–1402 (2010).

  9. 9.

    , , & Diverse groups of plant RNA and DNA viruses share related movement proteins that may possess chaperone-like activity. J. Gen. Virol. 72, 2895–2903 (1991).

  10. 10.

    , & Poised for contagion: evolutionary origins of the infectious abilities of invertebrate retroviruses. Genome Res. 10, 1307–1318 (2000). Along with reference 45, this study blurs the boundary between retrotransposons and retroviruses and suggests an evolutionary continuum between the two.

  11. 11.

    & Endogenous pararetroviruses: two-faced travelers in the plant genome. Trends Plant Sci. 11, 485–491 (2006).

  12. 12.

    , , & Characterization and genomic analysis of tobacco vein clearing virus, a plant pararetrovirus that is transmitted vertically and related to sequences integrated in the host genome. J. Gen. Virol. 81, 1579–1585 (2000).

  13. 13.

    et al. A single Banana streak virus integration event in the banana genome as the origin of infectious endogenous pararetrovirus. J. Virol. 82, 6697–6710 (2008).

  14. 14.

    The evolution of endogenous viral elements. Cell Host Microbe 10, 368–377 (2011).

  15. 15.

    et al. Recombination of retrotransposon and exogenous RNA virus results in nonretroviral cDNA integration. Science 323, 393–396 (2009).

  16. 16.

    & The evolution of novel fungal genes from non-retroviral RNA viruses. BMC Biol. 7, 88 (2009).

  17. 17.

    et al. Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature 463, 84–87 (2010). This was one of the first reports of non-retroviral EVEs in mammalian genomes and an experimental demonstration that Borna disease virus DNA can spontaneously integrate in the genome of human infected cells.

  18. 18.

    & Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration. Proc. Natl Acad. Sci. USA 101, 11135–11140 (2004).

  19. 19.

    & Genomic fossils calibrate the long-term evolution of hepadnaviruses. PLoS Biol. 8, e1000495 (2010). This paper provides a clear illustration of the discrepancy between short-term and long-term evolutionary rates of a virus family.

  20. 20.

    , & Sequences from ancestral single-stranded DNA viruses in vertebrate genomes: the parvoviridae and circoviridae are more than 40 to 50 million years old. J. Virol. 84, 12458–12462 (2010).

  21. 21.

    , & Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes. PLoS Pathog. 6, e1001030 (2010).

  22. 22.

    & Virus evolution: how far does the double β-barrel viral lineage extend? Nature Rev. Microbiol. 6, 941–948 (2008).

  23. 23.

    & Evolutionary analysis of the dynamics of viral infectious disease. Nature Rev. Genet. 10, 540–550 (2009).

  24. 24.

    Evolutionary history and phylogeography of human viruses. Annu. Rev. Microbiol. 62, 307–328 (2008). The above two references provide an excellent review of the concepts and methods used to delineate the epidemiological dynamics of clinically relevant viruses.

  25. 25.

    , , , & Insights into the evolutionary history of an emerging livestock pathogen: porcine circovirus 2. J. Virol. 83, 12813–12821 (2009).

  26. 26.

    et al. Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proc. Natl Acad. Sci. USA. 86, 7059–7062 (1989).

  27. 27.

    , , , & Macroevolution of complex retroviruses. Science 325, 1512 (2009).

  28. 28.

    , , , & Identification of a RELIK orthologue in the European hare (Lepus europaeus) reveals a minimum age of 12 million years for the lagomorph lentiviruses. Virology 384, 7–11 (2009).

  29. 29.

    & Endogenous lentiviruses in the ferret genome. J. Virol. 86, 3383–3385 (2012).

  30. 30.

    , & Rates of evolutionary change in viruses: patterns and determinants. Nature Rev. Genet. 9, 267–276 (2008).

  31. 31.

    et al. Evolutionary time-scale of the begomoviruses: evidence from integrated sequences in the Nicotiana genome. PLoS ONE 6, e19193 (2011).

  32. 32.

    et al. Time-dependent rates of molecular evolution. Mol. Ecol. 20, 3087–3101 (2011).

  33. 33.

    , , & Time—the emerging dimension of plant virus studies. J. Gen. Virol. 91, 13–22 (2010).

  34. 34.

    & Purifying selection can obscure the ancient age of viral lineages. Mol. Biol. Evol. 28, 3355–3365 (2011).

  35. 35.

    , , & Rates of spontaneous mutation. Genetics 148, 1667–1686 (1998).

  36. 36.

    & The evolution, distribution and diversity of endogenous retroviruses. Virus Genes. 26, 291–315 (2003).

  37. 37.

    & Effects of retroviruses on host genome function. Annu. Rev. Genet. 42, 709–732 (2008).

  38. 38.

    & Coevolution of retroelements and tandem zinc finger genes. Genome Res. 21, 1800–1812 (2011). This paper reports a striking correlation in the number and evolutionary emergence of KRAB-ZNF genes and ERVs within a wide range of vertebrate genomes.

  39. 39.

    & Dynamic control of endogenous retroviruses during development. Virology 411, 273–287 (2011).

  40. 40.

    et al. Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr. Biol. 11, 1531–1535 (2001).

  41. 41.

    et al. A human genome structural variation sequencing resource reveals insights into mutational mechanisms. Cell 143, 837–847 (2010).

  42. 42.

    et al. Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans. PLoS ONE 6, e20234 (2011).

  43. 43.

    , , & LINE-1 elements in structural variation and disease. Annu. Rev. Genomics Hum. Genet. 12, 187–215 (2011).

  44. 44.

    et al. Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line. PLoS Genet. 2, e2 (2006).

  45. 45.

    et al. An infectious progenitor for the murine IAP retrotransposon: emergence of an intracellular genetic parasite from an ancient retrovirus. Genome Res. 18, 597–609 (2008). See summary for reference 10.

  46. 46.

    , , , & Genome-wide assessments reveal extremely high levels of polymorphism of two active families of mouse endogenous retroviral elements. PLoS Genet. 4, e1000007 (2008).

  47. 47.

    et al. Sequence-based characterization of structural variation in the mouse genome. Nature. 477, 326–329 (2011).

  48. 48.

    et al. A novel active endogenous retrovirus family contributes to genome variability in rat inbred strains. Genome Res. 20, 19–27 (2010).

  49. 49.

    & Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nature Genet. 29, 487–489 (2001).

  50. 50.

    et al. Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses. Hum. Mol. Genet. 9, 2291–2296 (2000).

  51. 51.

    et al. HERV-mediated genomic rearrangement of EYA1 in an individual with branchio-oto-renal syndrome. Am. J. Med. Genet. 152A, 2854–2860 (2010).

  52. 52.

    et al. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 448, 595–599 (2007).

  53. 53.

    , & Endogenous retroviral LTRs as promoters for human genes: a critical assessment. Gene 448, 105–114 (2009).

  54. 54.

    , & Keeping active endogenous retroviral-like elements in check: the epigenetic perspective. Cell. Mol. Life Sci. 65, 3329–3347 (2008).

  55. 55.

    , & Distributions of transposable elements reveal hazardous zones in mammalian introns. PLoS Comput. Biol. 7, e1002046 (2011).

  56. 56.

    et al. Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A. Genes Dev. 25, 594–607 (2011). This provides an explicit demonstration of how the epigenetic machinery repressing ERV expression may be co-opted for the coordinated control of neighbouring host gene expression in early mammalian development.

  57. 57.

    et al. Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nature Med. 16, 571–579 (2010).

  58. 58.

    et al. Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray. J. Virol. 79, 341–352 (2005).

  59. 59.

    The regulated retrotransposon transcriptome of mammalian cells. Nature Genet. 41, 563–571 (2009).

  60. 60.

    , , & Endogenous retrovirus drives hitherto unknown proapoptotic p63 isoforms in the male germ line of humans and great apes. Proc. Natl Acad. Sci. USA 108, 3624–3629 (2011).

  61. 61.

    , , & Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet. 19, 530–536 (2003).

  62. 62.

    , & Retroviral promoters in the human genome. Bioinformatics 24, 1563–1567 (2008). References 59, 61 and 62 provide compelling evidence for an extensive, tightly regulated and lineage-specific ERV-derived transcriptome in mammals.

  63. 63.

    et al. Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev. Cell 7, 597–606 (2004).

  64. 64.

    , & Human cis natural antisense transcripts initiated by transposable elements. Trends Genet. 24, 53–56 (2008).

  65. 65.

    & RNA as a flexible scaffold for proteins: yeast telomerase and beyond. Cold Spring Harb. Symp. Quant. Biol. 71, 217–224 (2006).

  66. 66.

    , & A global view of genomic information—moving beyond the gene and the master regulator. Trends Genet. 26, 21–28 (2010).

  67. 67.

    & Modular regulatory principles of large noncoding RNAs. Nature 482, 339–346 (2012).

  68. 68.

    & Gene regulation for higher cells: a theory. Science 165, 349–357 (1969).

  69. 69.

    Transposable elements and the evolution of regulatory networks. Nature Rev. Genet. 9, 397–405 (2008).

  70. 70.

    , , & Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals. Nature Genet. 43, 1154–1159 (2011).

  71. 71.

    et al. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc. Natl Acad. Sci. USA 104, 18613–18618 (2007).

  72. 72.

    et al. The origins and evolution of the p53 family of genes. Cold Spring Harb. Perspect. Biol. 2, a001198 (2010).

  73. 73.

    et al. Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nature Genet. 42, 631–634 (2010).

  74. 74.

    et al. Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species. Genome Res. 20, 804–815 (2010). References 71, 73 and 74 show how transcription factor binding sites dispersed by ERV wire extensive gene regulatory networks in a lineage-specific fashion.

  75. 75.

    & Retroelements and the human genome: new perspectives on an old relation. Proc. Natl Acad. Sci. USA 101, 14572–14579 (2004).

  76. 76.

    & The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases. Clin. Rev. Allergy Immunol. 39, 51–61 (2010).

  77. 77.

    & Beneficial and detrimental effects of human endogenous retroviruses. Int. J. Cancer 126, 306–314 (2010).

  78. 78.

    & Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23, 5293–5300 (2003).

  79. 79.

    et al. Characterization of human endogenous retroviral elements in the blood of HIV-1-infected individuals. J. Virol. 86, 262–276 (2012).

  80. 80.

    et al. Interferon-α-induced endogenous superantigen. A model linking environment and autoimmunity. Immunity 15, 591–601 (2001).

  81. 81.

    , , & Coevolution of endogenous betaretroviruses of sheep and their host. Cell. Mol. Life Sci. 65, 3422–3432 (2008).

  82. 82.

    , , , & Receptor usage and fetal expression of ovine endogenous betaretroviruses: implications for coevolution of endogenous and exogenous retroviruses. J. Virol. 77, 749–753 (2003).

  83. 83.

    et al. Late viral interference induced by transdominant Gag of an endogenous retrovirus. Proc. Natl Acad. Sci. USA 101, 11117–11122 (2004).

  84. 84.

    , , & Origin, antiviral function and evidence for positive selection of the gammaretrovirus restriction gene Fv1 in the genus Mus. Proc. Natl Acad. Sci. USA 106, 3259–3263 (2009).

  85. 85.

    et al. Ordered assembly of murine leukemia virus capsid protein on lipid nanotubes directs specific binding by the restriction factor, Fv1. Proc. Natl Acad. Sci. USA 108, 5771–5776 (2011).

  86. 86.

    et al. A paradigm for virus-host coevolution: sequential counter-adaptations between endogenous and exogenous retroviruses. PLoS Pathog. 3, e170 (2007). This paper provides a comprehensive characterization of the various events that took place during the molecular arms race between domesticated endogenous betaretroviruses and their exogenous counterparts in sheep.

  87. 87.

    & Positive selection of Iris, a retroviral envelope-derived host gene in Drosophila melanogaster. PLoS Genet. 1, e44 (2005).

  88. 88.

    , , & Evolutionary maintenance of filovirus-like genes in bat genomes. BMC Evol. Biol. 11, 336 (2011).

  89. 89.

    et al. Widespread endogenization of densoviruses and parvoviruses in animal and human genomes. J. Virol. 85, 9863–9876 (2011).

  90. 90.

    , , & No evidence for natural selection on endogenous borna-like nucleoprotein elements after the divergence of Old World and New World monkeys. PLoS ONE 6, e24403 (2011).

  91. 91.

    et al. Fossil rhabdoviral sequences integrated into arthropod genomes: ontogeny, evolution, and potential functionality. Mol. Biol. Evol. 29, 381–390 (2012).

  92. 92.

    & The evolution, regulation, and function of placenta-specific genes. Annu. Rev. Cell Dev. Biol. 24, 159–181 (2008).

  93. 93.

    , , & Evolution of human endogenous retroviral sequences: a conceptual account. Cell. Mol. Life Sci. 65, 3348–3365 (2008).

  94. 94.

    et al. Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene. Proc. Natl Acad. Sci. USA 106, 12127–12132 (2009).

  95. 95.

    et al. A pair of co-opted retroviral envelope syncytin genes is required for formation of the two-layered murine placental syncytiotrophoblast. Proc. Natl Acad. Sci. USA 108, e1164–e1173 (2011). The above two references provide genetic evidence for an essential role of two env-derived murine syncytins in placenta formation.

  96. 96.

    et al. Endogenous retroviruses regulate periimplantation placental growth and differentiation. Proc. Natl Acad. Sci. USA 103, 14390–14395 (2006).

  97. 97.

    Hypothesis for heritable, anti-viral immunity in crustaceans and insects. Biol. Direct 4, 32 (2009).

  98. 98.

    & Analyzing protein structure and function using ancestral gene reconstruction. Curr. Opin. Struct. Biol. 20, 360–366 (2010).

  99. 99.

    , , & Discovery and analysis of the first endogenous lentivirus. Proc. Natl Acad. Sci. USA 104, 6261–6265 (2007).

  100. 100.

    et al. A transitional endogenous lentivirus from the genome of a basal primate and implications for lentivirus evolution. Proc. Natl Acad. Sci. USA 105, 20362–20367 (2008).

  101. 101.

    , , , & Gene acquisition in HIV and SIV. Nature 383, 586–587 (1996).

  102. 102.

    et al. Characterization and comparison of recombinant simian immunodeficiency virus from drill (Mandrillus leucophaeus) and mandrill (Mandrillus sphinx) isolates. J. Virol. 77, 4867–4880 (2003).

  103. 103.

    , & Complex evolutionary history of primate lentiviral vpr genes. Virology 240, 232–237 (1998).

  104. 104.

    , , & Parallel germline infiltration of a lentivirus in two Malagasy lemurs. PLoS Genet. 5, e1000425 (2009).

  105. 105.

    , , & Complement component C4 gene intron 9 as a phylogenetic marker for primates: long terminal repeats of the endogenous retrovirus ERV-K(C4) are a molecular clock of evolution. Immunogenetics 42, 41–52 (1995).

  106. 106.

    & On the estimation of the insertion time of LTR retrotransposable elements. Mol. Biol. Evol. 27, 896–904 (2010).

  107. 107.

    & Improved integration time estimation of endogenous retroviruses with phylogenetic data. PLoS ONE 6, e14745 (2011).

  108. 108.

    & Embryonic stem cells use ZFP809 to silence retroviral DNAs. Nature 458, 1201–1204 (2009).

  109. 109.

    & Silencing of endogenous retroviruses: when and why do histone marks predominate? Trends Biochem. Sci. 16 Dec 2011 (doi: 10.1016/j.tibs.2011.11.006).

  110. 110.

    et al. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463, 237–240 (2010).

  111. 111.

    et al. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature 464, 927–931 (2010). References 108–111 unveil fundamental components and principles of a recently discovered system of proviral silencing in mammal ESCs.

  112. 112.

    , , & Rapid sequence and expression divergence suggest selection for novel function in primate-specific KRAB-ZNF genes. Mol. Biol. Evol. 27, 2606–2617 (2010).

  113. 113.

    et al. Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res. 16, 1548–1556 (2006).

  114. 114.

    & Reconstitution of an infectious human endogenous retrovirus. PLoS Pathog. 3, e10 (2007). The above two references reconstitute an infectious progenitor for a human endogenous retrovirus.

  115. 115.

    , & Evidence for restriction of ancient primate gammaretroviruses by APOBEC3 but not TRIM5α proteins. PLoS Pathog. 4, e1000181 (2008).

  116. 116.

    , & Restriction of an extinct retrovirus by the human TRIM5α antiviral protein. Science. 316, 1756–1758 (2007).

  117. 117.

    , & Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLoS Biol. 2, e275 (2004).

  118. 118.

    et al. Unique spectrum of activity of prosimian TRIM5α against exogenous and endogenous retroviruses. J. Virol. 85, 4173–4183 (2011).

  119. 119.

    , & Identification of a receptor for an extinct virus. Proc. Natl Acad. Sci. USA 107, 19496–19501 (2010).

  120. 120.

    et al. Structural and functional analysis of prehistoric lentiviruses uncovers an ancient molecular interface. Cell Host Microbe 8, 248–259 (2010).

  121. 121.

    & Host restriction factors blocking retroviral replication. Annu. Rev. Genet. 42, 143–163 (2008).

  122. 122.

    , , & Positive selection of primate TRIM5α identifies a critical species-specific retroviral restriction domain. Proc. Natl Acad. Sci. USA 102, 2832–2837 (2005). This study provides a vivid demonstration of the power of evolutionary sequence analysis to shed crucial insight into the interaction of host restriction factors with their viral targets.

  123. 123.

    , & Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein. PLoS Genet. 4, e21 (2008).

  124. 124.

    et al. Persistent Hz-1 virus infection in insect cells: evidence for insertion of viral DNA into host chromosomes and viral infection in a latent status. J. Virol. 73, 128–139 (1999).

  125. 125.

    et al. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc. Natl Acad. Sci. USA 107, 5563–5568 (2010).

  126. 126.

    & Herpesviruses and chromosomal integration. J. Virol. 84, 12100–12109 (2010).

  127. 127.

    , , & Polydnavirus hidden face: the genes producing virus particles of parasitic wasps. J. Invertebr. Pathol. 101, 194–203 (2009).

  128. 128.

    , , & Persistent virus integration into the genome of its algal host, Ectocarpus siliculosus (Phaeophyceae). J. Gen. Virol. 80, 1367–1370 (1999).

  129. 129.

    et al. The Ectocarpus genome and the independent evolution of multicellularity in brown algae. Nature 465, 617–621 (2010).

  130. 130.

    et al. Widespread horizontal gene transfer from circular single-stranded DNA viruses to eukaryotic genomes. BMC Evol. Biol. 11, 276 (2011).

  131. 131.

    , , & Integration of multiple repeats of geminiviral DNA into the nuclear genome of tobacco during evolution. Proc. Natl Acad. Sci. USA 93, 759–764 (1996).

  132. 132.

    et al. Analysis of multiple copies of geminiviral DNA in the genome of four closely related Nicotiana species suggest a unique integration event. Plant. Mol. Biol. 35, 313–321 (1997).

  133. 133.

    , & Discovery and characterization of mammalian endogenous parvoviruses. J. Virol. 84, 12628–12635 (2010).

  134. 134.

    & Infectious hypodermal and hematopoietic necrosis virus (IHHNV)-related sequences in the genome of the black tiger prawn Penaeus monodon from Africa and Australia. Virus Res. 118, 185–191 (2006).

  135. 135.

    et al. Widespread horizontal gene transfer from double-stranded RNA viruses to eukaryotic nuclear genomes. J. Virol. 84, 11876–11887 (2010).

  136. 136.

    & Evolutionary capture of viral and plasmid DNA by yeast nuclear chromosomes. Eukaryot. Cell 8, 1521–1531 (2009).

  137. 137.

    , & Reciprocal sequence exchange between non-retro viruses and hosts leading to the appearance of new host phenotypes. Virology 362, 342–349 (2007).

  138. 138.

    et al. Sequences of flavivirus-related RNA viruses persist in DNA form integrated in the genome of Aedes spp. mosquitoes. J. Gen. Virol. 85, 1971–1980 (2004).

  139. 139.

    , , , & Detection of novel insect flavivirus sequences integrated in Aedes albopictus (Diptera: Culicidae) in Northern Italy. Virol. J. 6, 93 (2009).

  140. 140.

    & Occurrence of a DNA sequence of a non-retro RNA virus in a host plant genome and its expression: evidence for recombination between viral and host RNAs. Virology 332, 614–622 (2005).

  141. 141.

    , & Filoviruses are ancient and integrated into mammalian genomes. BMC Evol. Biol. 10, 193 (2010).

  142. 142.

    et al. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J. Virol. 74, 3321–3329 (2000).

  143. 143.

    et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403, 785–789 (2000).

  144. 144.

    , , & Genome wide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc. Natl Acad. Sci. USA 100, 13013–13018 (2003).

  145. 145.

    , , & Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: a new “syncytin” in a third order of mammals. Retrovirology 6, 107 (2009).

  146. 146.

    et al. Ancestral capture of syncytin-Car1, a fusogenic endogenous retroviral envelope gene ivolved in placentation and conserved in Carnivora. Proc. Natl Acad. Sci. USA 109, e432–e441 (2012).

  147. 147.

    , & Functional characterization of two newly identified human endogenous retrovirus coding envelope genes. Retrovirology 2, 19 (2005).

  148. 148.

    , , & Positional cloning of the mouse retrovirus restriction gene Fv1. Nature 382, 826–829 (1996).

  149. 149.

    & CGIN1: a retroviral contribution to mammalian genomes. Mol. Biol. Evol. 26, 2167–2170 (2009).

  150. 150.

    & A cellular Drosophila melanogaster protein with similarity to baculovirus F envelope fusion proteins. J. Virol. 79, 7979–7989 (2005).

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Acknowledgements

We apologize to many colleagues who have produced primary research on the topic that could not be cited or discussed owing to space limitations. We thank the three anonymous reviewers for their constructive comments and useful suggestions. This work was supported by grant GM77582 from the US National Institutes of Health to C.F.

Author information

Affiliations

  1. Department of Biology, University of Texas, Arlington, Texas 76016, USA.

    • Cédric Feschotte
  2. Université de Poitiers, UMR CNRS 7267, Ecologie et Biologie des Interactions, Equipe Ecologie Evolution Symbiose, France.

    • Clément Gilbert

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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Cédric Feschotte or Clément Gilbert.

Glossary

Horizontally

In the context of genetic information, horizontal transmission is the transfer of genetic material by means other than sex.

Vertical transmission

Sexual transmission of genetic material from parent to offspring.

Fixation

A mutation reaches fixation when it is present in all individuals of a given species.

Transposable elements

Pieces of DNA (typically genomic elements) that are able to move from one locus to another, often duplicating themselves in the process.

Reverse transcription

Synthesis of DNA from an RNA template.

Retrotransposon

Mobile intracellular genetic elements that replicate via reverse transcription of an RNA intermediate.

Envelope

(Env). A glycoprotein encoded by many viruses that binds to host receptors located on the cell surface in order to promote viral entry.

Non-homologous end joining

A DNA double-strand break repair pathway that does not make use of a template and is therefore intrinsically error-prone.

Zoonotic

Describes a virus that can be transmitted between animals and humans or vice versa.

Mutational saturation

A given site in a DNA sequence is saturated when the number of observed or inferred mutations is lower than the number of mutations that truly occurred at this site.

Latency

A period during which a virus replicates at a low rate without causing any symptoms to the host.

Saltational

A saltational change is a profound and rapid change in the evolutionary dynamics of a viral lineage.

Phylodynamic

The joint study of the epidemiological and evolutionary dynamics of a virus.

Provirus

The integrated form of a retrovirus.

Reinfection

Repeated infection of the germ cells of the individual carrying a provirus, with possible horizontal transmission to other individuals.

Dimorphic

Full-length insertion present in some individuals but absent in others.

Superantigen

A class of antigens that cause nonspecific activation and uncontrolled proliferation of T cells, often resulting in a chronic inflammatory response.

Gag

A retroviral protein that is one of the structural proteins of the viral capsid.