HERV-K Polymorphisms in Human Populations.
Jennifer F. Hughes and John M. Coffin Department of Molecular Biology and
Microbiology, Tufts University, Boston MA
Human endogenous
retroviruses (HERVs) are a potential source for the generation of genetic
diversity in the human genome. While the vast majority of these elements are
fixed in the genome and have been inactivated over time by the accumulation of
deleterious mutations or solo LTR formation, several members of the HERV-K
family have been identified that remain nearly intact and probably represent
recent integration events. To determine if HERV-K elements have caused recent
changes in the human genome, we have undertaken a study of the level of HERV-K
polymorphism that exists in the human population using a high-resolution in gel
hybridization (unblotting) technique. Out of 13 human-specific HERV-K elements
analyzed in 18 individuals, we found that four exhibit insertional polymorphism
in that the unoccupied integration site is found in some individuals, and that
solo LTRs have formed at five of these loci. These results imply that there has
been some recent insertion of HERV-K proviruses, but the distribution among
widely separated populations implies that all insertions must have taken place
over 100,000 years ago. They also enable the first estimation of HERV solo LTR
formation in the human genome and may indicate that these events occur much more
frequently than previously described in inbred mice. Detailed sequence analysis
of one provirus shows that solo LTR formation occurred at least three separate
times in recent history. An unoccupied preintegration site was also present at
this locus in two individuals, indicating that even though the age of this
provirus is estimated to be about 1.2 million years, it has not yet become fixed
in the human population.