Expansion of a novel endogenous retrovirus throughout the pericentromeres of modern humans

Joseph Zahn, Mark H. Kaplan, Sabrina Fischer, Manhong Dai, Fan Meng, Anjan Kumar Saha, Patrick Cervantes, Susana M. Chan, Derek Dube, Gilbert S. Omenn, David M. Markovitz, Rafael Contreras-Galindo

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: Approximately 8% of the human genome consists of sequences of retroviral origin, a result of ancestral infections of the germ line over millions of years of evolution. The most recent of these infections is attributed to members of the human endogenous retrovirus type-K (HERV-K) (HML-2) family. We recently reported that a previously undetected, large group of HERV-K (HML-2) proviruses, which are descendants of the ancestral K111 infection, are spread throughout human centromeres. Results: Studying the genomes of certain cell lines and the DNA of healthy individuals that seemingly lack K111, we discover new HERV-K (HML-2) members hidden in pericentromeres of several human chromosomes. All are related through a common ancestor, termed K222, which is a virus that infected the germ line approximately 25 million years ago. K222 exists as a single copy in the genomes of baboons and high order primates, but not New World monkeys, suggesting that progenitor K222 infected the primate germ line after the split between New and Old World monkeys. K222 exists in modern humans at multiple loci spread across the pericentromeres of nine chromosomes, indicating it was amplified during the evolution of modern humans. Conclusions: Copying of K222 may have occurred through recombination of the pericentromeres of different chromosomes during human evolution. Evidence of recombination between K111 and K222 suggests that these retroviral sequences have been templates for frequent cross-over events during the process of centromere recombination in humans.

Original languageEnglish (US)
Article number74
JournalGenome biology
Volume16
Issue number1
DOIs
StatePublished - Apr 12 2015

Bibliographical note

Funding Information:
This work was supported by grant K22 CA177824 from the National Cancer Institute and a Research Supplement to Promote Diversity in Health-Related Research 3R01CA144043-03S1 from the National Institutes of Health (NIH) to R.C-G.; grant 05–5089 from the Concerned Parents for AIDS Research (CPFA) to M.H.K.; and by grant RO1 CA144043 from the National Institutes of Health to D.M.M. S. F. was supported by the fellowship MOV_CA_2013_1_10789 from the Programa de Desarrollo de Ciencias Básicas (PEDECIBA), Agencia Nacional de Investigación e Innovación (ANII) from the Uruguayan government. S.C. was supported by NIH Cellular and Molecular Biology Training Grant T32-GM007315. P.C. was supported by NIH Postbaccalaureate Research Education Program (PREP) grant R25GM086262-07. D.D. was supported by the Molecular Mechanisms of Microbial Pathogenesis Training Grant from the University of Michigan (5T32AI007528-13) and by NIH National Research Service Award (NRSA) grant 1F32AI106189-01. G.S.O. acknowledges support from NIH grants RM-08-029, P30U54ES017885, and UL1RR24986.

Publisher Copyright:
© 2015 Zahn et al.

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