title: The decline of human endogenous retroviruses: extinction and survival.
abstract: BACKGROUND
  Endogenous Retroviruses (ERVs) are retroviruses that over the course of evolution have integrated into germline cells and eventually become part of the host genome. They proliferate within the germline of their host, making up ~5% of the human and mouse genome sequences. Several lines of evidence have suggested a decline in the rate of ERV integration into the human genome in recent evolutionary history but this has not been investigated quantitatively or possible causes explored.
  
  
  RESULTS
  By dating the integration of ERV loci in 40 mammal species, we show that the human genome and that of other hominoids (great apes and gibbons) have experienced an approximately four-fold decline in the ERV integration rate over the last 10 million years. A major cause is the recent extinction of one very large ERV lineage (HERV-H), which is responsible for most of the integrations over the last 30 million years. The decline however affects most other ERV lineages. Only about 10% of the decline might be attributed to an accompanying increase in body mass (a trait we have shown recently to be negatively correlated with ERV integration rate). Humans are unusual compared to related species - Old World monkeys, great apes and gibbons - in (a) having not acquired any new ERV lineages during the last 30 million years and (b) the possession of an old ERV lineage that has continued to replicate up until at least the last few hundred thousand years - the potentially medically significant HERVK(HML2).
  
  
  CONCLUSIONS
  The human genome shares with the genome of other great apes and gibbons a recent decline in ERV integration that is not typical of other primates and mammals. The human genome differs from that of related species both in maintaining up until at least recently a replicating old ERV lineage and in not having acquired any new lineages. We speculate that the decline in ERV integration in the human genome has been exacerbated by a relatively low burden of horizontally-transmitted retroviruses and subsequent reduced risk of endogenization.
authors: Gkikas
authors: G
authors: Magiorkinis
authors: Daniel
authors: D
authors: Blanco-Melo
authors: Robert
authors: R
authors: Belshaw
mesh_terms: D000818:Animals; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000502:physiology*; D019143:Evolution, Molecular; D006801:Humans; D011323:Primates; D016662:Virus Integration; D014779:Virus Replication
references: Proc Natl Acad Sci U S A. 2012 May 8;109(19):7385-90
references: 22529376
references: J Virol. 2014 Sep 1;88(17):9529-37
references: 24920817
references: J Virol. 1991 Jun;65(6):2816-28
references: 2033656
references: Emerg Microbes Infect. 2014 Jan;3(1):e7
references: 26038495
references: AIDS. 2012 Mar 27;26(6):659-73
references: 22441170
references: J Virol. 2000 Apr;74(8):3715-30
references: 10729147
references: J Virol. 2010 Feb;84(3):1464-76
references: 19906908
references: Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4894-9
references: 15044706
references: Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):803-8
references: 11792858
references: Annu Rev Genet. 2008;42:709-32
references: 18694346
references: J Virol. 2008 Sep;82(17):8762-70
references: 18562521
references: PLoS One. 2014;9(3):e92012
references: 24651676
references: J Virol. 2005 Oct;79(19):12507-14
references: 16160178
references: PLoS One. 2012;7(6):e40158
references: 22768246
references: Genome Res. 1999 Jun;9(6):525-40
references: 10400920
references: J Virol. 2012 Oct;86(19):10776-91
references: 22837215
references: PLoS One. 2013;8(8):e72756
references: 24023643
references: Curr Opin Virol. 2013 Dec;3(6):646-56
references: 24004725
references: J Clin Invest. 2007 Nov;117(11):3148-54
references: 17975656
references: Retrovirology. 2011;8:90
references: 22067224
references: PLoS Pathog. 2014 Jul;10(7):e1004214
references: 25033295
references: J Gen Virol. 2004 Nov;85(Pt 11):3305-12
references: 15483244
references: Bioessays. 2013 Sep;35(9):794-803
references: 23864388
references: J Virol. 2007 Sep;81(17):9437-42
references: 17581995
references: J Hum Evol. 2004 Jan;46(1):69-103
references: 14698685
references: J Virol. 2012 Oct;86(20):11194-208
references: 22855497
references: PLoS Biol. 2006 May;4(5):e88
references: 16683862
references: J Virol. 1997 May;71(5):3666-76
references: 9094640
references: Nat Immunol. 2014 May;15(5):415-22
references: 24747712
references: Mol Biol Evol. 2012 Aug;29(8):1969-73
references: 22367748
references: Nat Rev Microbiol. 2012 Jun;10(6):395-406
references: 22565131
references: Science. 2007 Jun 22;316(5832):1756-8
references: 17588933
references: J Anat. 2008 Apr;212(4):394-425
references: 18380863
references: Trends Genet. 2000 Jun;16(6):276-7
references: 10827456
references: J Immunol. 2012 Aug 1;189(3):1467-79
references: 22745376
references: Trends Microbiol. 1999 Nov;7(11):430; author reply 431-2
references: 10542419
references: J Gen Virol. 2004 Nov;85(Pt 11):3313-7
references: 15483245
references: Philos Trans R Soc Lond B Biol Sci. 2013 Sep 19;368(1626):20120504
references: 23938753
references: PLoS Pathog. 2008 Oct;4(10):e1000181
references: 18927623
references: Primates. 2009 Oct;50(4):311-9
references: 19506992
references: J Gen Virol. 2003 Dec;84(Pt 12):3233-8
references: 14645905
references: Nature. 2002 Dec 5;420(6915):520-62
references: 12466850
references: J Virol. 2008 Sep;82(17):8743-61
references: 18562517
references: Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10254-60
references: 10468595
references: Genome Biol. 2012;13(6):R45
references: 22703977
references: Gene. 2000 Apr 18;247(1-2):265-77
references: 10773466
references: Hum Genet. 1995 Aug;96(2):188-92
references: 7635468
references: Hum Nat. 2012 Mar;23(1):45-67
references: 22388772
references: Retrovirology. 2012;9(1):28
references: 22462797
references: Am Nat. 2010 Jun;175(6):727-38
references: 20394498
references: Virology. 2003 May 10;309(2):248-57
references: 12758172
references: Nature. 2005 Mar 17;434(7031):376-80
references: 15772660
references: PLoS Genet. 2011 Mar;7(3):e1001342
references: 21436896
references: Lancet. 2001 Dec 8;358(9297):1989-92
references: 11747942
references: J Infect Dis. 2011 May 1;203(9):1316-23
references: 21459818
references: Mob DNA. 2011 May 04;2(1):7
references: 21542922
references: J Virol. 1995 Sep;69(9):5917-24
references: 7543595
references: Mol Biol Evol. 2010 Apr;27(4):896-904
references: 19955475
references: Genome Res. 2003 May;13(5):838-44
references: 12727904
references: PLoS Pathog. 2007 Nov;3(11):e170
references: 17997604
references: PLoS Biol. 2005 Apr;3(4):e110
references: 15737067
references: Front Oncol. 2013 Sep 17;3:243
references: 24062992
references: Nature. 2009 Jul 23;460(7254):515-9
references: 19626114
references: J Mol Evol. 1994 Sep;39(3):306-14
references: 7932792
references: PLoS Pathog. 2008 Jul;4(7):e1000097
references: 18604273
references: J Virol. 2014 Oct;88(19):11108-20
references: 25056891
references: PLoS One. 2007;2(10):e1026
references: 17925874
references: BMC Evol Biol. 2007;7:214
references: 17996036
references: Nature. 2001 Feb 15;409(6822):860-921
references: 11237011