HERV-K(OLD): Ancestor sequences of the human endogenous retrovirus family HERV-K(HML-2)

Sequences homologous to the human endogenous retrovirus (HERV) family HERV- K(HML-2) are present in all Old World primate species. A previous study sho wed that a central region of the HERV-K(HML-2) gag genes in Hominoidea spec ies displays a 96-bp deletion compared to the gag genes in lower Old World primates. The more ancient HERV-K(HML-2) sequences present in lower Old Wor ld primates were apparently not conserved during hominoid evolution, as opp osed to the deletion variants. To further clarify the evolutionary origin o f the HERV-K(HML-2) family, we screened GenBank with the 96-bp gag-sequence characteristic of lower Old World primates and identified, to date, 10 hum an sequence entries harboring either full-length or partially deleted provi ral structures, probably representing remnants of a more ancient HERV-K(HML -2) variant. The high degree of mutations demonstrates the long-time presen ce of these HERV-K(OLD) proviruses in the genome. Nevertheless, they still belong to the HML-2 family as deduced from dot matrix and phylogenetic anal yses. We estimate, based on the family ages of integrated Alu elements and on long terminal repeat (LTR) divergence data, that the average age of HERV -K(OLD) proviruses is ca. 28 million years, supporting an integration time before the evolutionary split of Hominoidea from lower Old World primates. Analysis of HERV-K(OLD) LTR sequences led to the distinction of two subgrou ps, bout of which cluster with LTRs belonging to an evolutionarily older cl uster. Taken together, our data give further insight into the evolutionary history of the HERV-K(HML-2) family during primate evolution.