title: Haplotype analysis of the human endogenous retrovirus locus HERV-K(HML-2.HOM) and its evolutionary implications.
abstract: We and others recently identified an almost-intact human endogenous retrovirus (HERV), termed HERV-K(HML-2.HOM), that is usually organized as a tandem provirus. Studies on HERV proviral loci commonly rely on the analysis of single alleles being taken as representative for a locus. We investigated the frequency of HERV-K(HML-2.HOM) single and tandem alleles in various human populations. Our analysis revealed that another HERV-K(HML-2) locus, the so-called HERV-K(II) provirus, is also present as a tandem provirus allele in the human population. Proviral tandem formations were identified in various nonhuman primate species. We furthermore examined single nucleotide polymorphisms (SNPs) within the HERV-K(HML-2.HOM) proviral gag, prt, and pol genes, which all result in nonsense mutations. We identified four proviral haplotypes displaying different combinations of gag, prt, and pol SNPs. Haplotypes harboring completely intact proviral genes were not found. For the left provirus of the tandem arrangement a haplotype displaying intact gag and prt genes and a mutated pol was found in about two-thirds of individuals from different ethnogeographic origins. The same haplotype was always found in the right provirus. The various haplotypes point toward multiple recombination events between HERV-K(HML-2.HOM) proviruses. Based on these findings we derive a model for the evolution of the proviral locus since germ line integration.
authors.affiliation: Department of Human Genetics, Bulding 60, Medical Faculty, University of Saarland, 66421 Homburg, Germany. jens.mayer@uniklinik-saarland.de
authors.forename: Jens
authors.initials: J
authors.lastname: Mayer
authors.forename: Thomas
authors.initials: T
authors.lastname: Stuhr
authors.forename: Katrin
authors.initials: K
authors.lastname: Reus
authors.forename: Esther
authors.initials: E
authors.lastname: Maldener
authors.forename: Milena
authors.initials: M
authors.lastname: Kitova
authors.forename: Friedrich
authors.initials: F
authors.lastname: Asmus
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D000483:Alleles; D001483:Base Sequence; D020077:Endogenous Retroviruses / Q000235:genetics*; D019143:Evolution, Molecular; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011533:Proviruses / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid