DISTRIBUTION OF GENETIC POLYMORPHISMS IN HUMAN ENDOGENOUS RETRO VIRUSES AMONG VARIOUS ETHNIC POPULATIONS

Abstract

Human endogenous retroviruses (HERVs) are defective proviruses transmitted as stable Mendelian units vertically through the germline from one generation to the next. This project compared classes I (ERV3) and II (HERV-K) HERV env sequences among six divergent ethnic groups. Sequences related to human T-cell lymphotropic virus type-1 (HTLV-1) were used as out-group controls. Three novel single nucleotide polymorphisms (SNPs) were found in ERV3, and one in HERV-K. Both novel and published polymorphisms were screened on a panel of DNA representing six ethnic racial groups. SNPs tended to be population specific and, for the most part, in Hardy-Weinberg equilibrium. Primate DNA was sequenced at these polymorphic loci to determine sequence homology in the human-primate lineage. Divergent nucleotides were found in Class I (6.5%) and Class II (4.5%) HERVs. Phylogenetic analysis of ERV3 in the primate lineage showed humans of Asian and Amer-Indian descent to be more closely related than to other populations tested in this study. This study also re-evaluated copy number in ERV3, a reportedly single copy HERV. ERV3 was localized on chromosome 7 and Y by analysis of somatic cell hybrids. Southern blot analysis indicated two copies on each chromosome. Differences between copies on each hybrid were resolved by sequence analysis. No difference in sequence was detected in either the LTRs or env gene suggesting that the chromosome Y copy is a translocated copy from chromosome 7 which may have occurred during the generation of somatic cell hybrids.