Evolutionary History of the Proviruses HERV‐K 113 and HERV‐K 115


Human endogenous retroviruses are found throughout the genome, and most insertions predate human divergence from other primates. A small number are unique to humans and unfixed in the human genome. Much scientific interest has centered on the human endogenous retroviruses (HERV)‐K113 and HERV‐K115 insertions. The evolutionary history of these two endogenous proviruses is complex, and the estimates of both of their insertion times have recently been revised. HERV‐K113 inserted into the genome sometime between 0.8 and 1.3 million years ago (Ma), while HERV‐K115 was inserted into the genome sometime between 1.1 and 1.9 Ma. Both insertions occurred during a time when Homo erectus is believed to have been the dominant hominin species.

Key Concepts:

  • HERV‐K113 and HERV‐K115 are members of the HML‐2 group of endogenous retroviruses and neither insertion is fixed in the modern human genome.

  • Despite their unfixed state, HERV‐K113 and HERV‐K115 are not recent insertions into the human genome.

  • HERV‐K113 inserted into the genome sometime between 0.8 and 1.3 Ma.

  • HERV‐K115 inserted into the genome sometime between 1.1 and 1.9 Ma.

  • Despite a possibly wide separation in their insertion times, HERV‐K113 and HERV‐K115 are highly similar in sequence.

  • Both insertions occurred during a time when Homo erectus is believed to have been the dominant hominin species.

Keywords: endogenous retrovirus; HERV‐K113; HERV‐K115; hominin

Figure 1.

Timeline of hominin evolution and HERV‐K113/K115 insertions. Dates are shown in millions of years ago (Ma). Insertion times for K113 and K115 were estimated in Jha et al. (). Dates for the emergence of modern Homo sapiens were described in McDougall et al. (); White et al. (). Dates for the emergence of Homo erectus were described in Clark et al. ().



Agoni L, Golden A, Guha C and Lenz J (2012) Neandertal and denisovan retroviruses. Current Biology: CB 22(11): R437–R438. doi:10.1016/j.cub.2012.04.049.

Barbulescu M, Turner G, Seaman MI et al. (1999) Many human endogenous retrovirus K (HERV‐K) proviruses are unique to humans. Current Biology: CB 9(16): 861–868.

Barbulescu M, Turner G, Su M et al. (2001) A HERV‐K provirus in chimpanzees, bonobos and gorillas, but not humans. Current Biology: CB 11(10): 779–783.

Clark JD, de Heinzelin J, Schick KD et al. (1994) African homo erectus: old radiometric ages and young oldowan assemblages in the middle awash valley, Ethiopia. Science 264(5167): 1907–1910.

Dangel AW, Baker BJ, Mendoza AR and Yu CY (1995) 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(1): 41–52.

Dewannieux M, Harper F, Richaud A et al. (2006) Identification of an infectious progenitor for the multiple‐copy HERV‐K human endogenous retroelements. Genome Research 16(12): 1548–1556. doi:10.1101/gr.5565706.

Gilboa E, Mitra SW, Goff S and Baltimore D (1979) A detailed model of reverse transcription and tests of crucial aspects. Cell 18(1): 93–100.

Jha AR, Nixon DF, Rosenberg MG et al. (2011) Human endogenous retrovirus K106 (HERV‐K106) was infectious after the emergence of anatomically modern humans. PLoS One 6(5): e20234. doi:10.1371/journal.pone.0020234.

Jha AR, Pillai SK, York VA et al. (2009) Cross‐sectional dating of novel haplotypes of HERV‐K 113 and HERV‐K 115 indicate these proviruses originated in Africa before homo sapiens. Molecular Biology and Evolution 26(11): 2617–2626. doi:10.1093/molbev/msp180.

Lander ES, Linton LM, Birren B et al. (2001) Initial sequencing and analysis of the human genome. Nature 409(6822): 860–921. doi:10.1038/35057062.

Lee YN and Bieniasz PD (2007) Reconstitution of an infectious human endogenous retrovirus. PLoS Pathogens 3(1): e10. doi:10.1371/journal.ppat.0030010.

Lewinski MK and Bushman FD (2005) Retroviral DNA integration – mechanism and consequences. Advances in Genetics 55, 147–181. doi:10.1016/S0065‐2660(05)55005‐3.

Macfarlane C and Simmonds P (2004) Allelic variation of HERV‐K(HML‐2) endogenous retroviral elements in human populations. Journal of Molecular Evolution 59(5): 642–656. doi:10.1007/s00239‐004‐2656‐1.

Marchi E, Kanapin A, Byott M, Magiorkinis G and Belshaw R (2013) Neanderthal and denisovan retroviruses in modern humans. Current Biology: CB 23(22): R994–R995. doi:10.1016/j.cub.2013.10.028.

McDougall I, Brown FH and Fleagle JG (2005) Stratigraphic placement and age of modern humans from Kibish, Ethiopia. Nature 433(7027): 733–736. doi:10.1038/nature03258.

Meyer M, Kircher M, Gansauge MT et al. (2012) A high‐coverage genome sequence from an archaic denisovan individual. Science (New York, NY) 338(6104): 222–226. doi:10.1126/science.1224344.

Moyes DL, Goris A, Ban M et al. (2008) HERV‐K113 is not associated with multiple sclerosis in a large family‐based study. AIDS Research and Human Retroviruses 24(3): 363–365. doi:10.1089/aid.2007.0196.

Moyes DL, Martin A, Sawcer S et al. (2005) The distribution of the endogenous retroviruses HERV‐K113 and HERV‐K115 in health and disease. Genomics 86(3): 337–341. doi:10.1016/j.ygeno.2005.06.004.

Ono M, Yasunaga T, Miyata T and Ushikubo H (1986) Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome. Journal of Virology 60(2): 589–598.

Ribet D, Harper F, Dupressoir A et al. (2008) An infectious progenitor for the murine IAP retrotransposon: Emergence of an intracellular genetic parasite from an ancient retrovirus. Genome Research 18(4): 597–609. doi:10.1101/gr.073486.107.

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

Telesnitsky A and Goff SP (1997) Reverse transcriptase and the generation of retroviral DNA. Overview of reverse transcription. In: Coffin JM, Hughes SH and Varmus HE (eds) Retroviruses. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. Available at: http://www.ncbi.nlm.nih.gov/books/NBK19424/

Turner G, Barbulescu M, Su M et al. (2001) Insertional polymorphisms of full‐length endogenous retroviruses in humans. Current Biology: CB 11 (19): 1531–1535.

White TD, Asfaw B, DeGusta D et al. (2003) Pleistocene homo sapiens from middle Awash, Ethiopia. Nature 423(6941): 742–747. doi:10.1038/nature01669.

Worobey M, Gemmel M, Teuwen DE et al. (2008) Direct evidence of extensive diversity of HIV‐1 in Kinshasa by 1960. Nature 455(7213): 661–664. doi:10.1038/nature07390.

Further Reading

Bannert N and Kurth R (2004) Retroelements and the human genome: new perspectives on an old relation. Proceedings of the National Academy of Sciences of the USA 101(Suppl. 2): 14572–14579. doi:10.1073/pnas.0404838101. PMCID: PMC521986.

Hohn O, Hanke K and Bannert N (2013) HERV‐K(HML‐2), the best preserved family of HERVs: endogenization, expression, and implications in health and disease. Frontiers in Oncology 3: 246. doi:10.3389/fonc.2013.00246. PMCID: PMC3778440.

van der Kuyl AC (2012) HIV infection and HERV expression: a review. Retrovirology 9: 6. doi:10.1186/1742-4690-9-6. PMCID: PMC3311604.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Garrison, Keith E, Nixon, Douglas F, Pillai, Satish K, and Jha, Aashish R(Sep 2014) Evolutionary History of the Proviruses HERV‐K 113 and HERV‐K 115. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022876]