title: Discovery of unfixed endogenous retrovirus insertions in diverse human populations.
abstract: Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from <0.0005 to >0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109;
authors.forename: Julia Halo
authors.initials: JH
authors.lastname: Wildschutte
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;
authors.forename: Zachary H
authors.initials: ZH
authors.lastname: Williams
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;
authors.forename: Meagan
authors.initials: M
authors.lastname: Montesion
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111;
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Subramanian
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111; john.coffin@tufts.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Coffin
mesh_terms: D000483:Alleles; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D020079:Terminal Repeat Sequences
keywords: 1000 Genomes Project; HERV-K; HML-2; Human Genome Diversity Project; human endogenous retrovirus