Human Endogenous Retroviral Elements as Indicators of Ectopic Recombination Events in the Primate Genome

Abstract

HERV elements make up a significant fraction of the human genome and, as interspersed repetitive elements, have the capacity to provide substrates for ectopic recombination and gene conversion events. To understand the extent to which these events occur and gain further insight into the complex evolutionary history of these elements in our genome, we undertook a phylogenetic study of the long terminal repeat sequences of 15 HERV-K(HML-2) elements in various primate species. This family of human endogenous retroviruses first entered the primate genome between 35 and 45 million years ago. Throughout primate evolution, these elements have undergone bursts of amplification. From this analysis, which is the largestscale study of HERV sequence dynamics during primate evolution to date, we were able to detect intraelement gene conversion and recombination at five HERV-K loci. We also found evidence for replacement of an ancient element by another HERV-K provirus, apparently reflecting an occurrence of retroviral integration by homologous recombination. The high frequency of these events casts doubt on the accuracy of integration time estimates based only on divergence between retroelement LTRs.

A transitional endogenous lentivirus from the genome of a basal primate and implications for lentivirus evolution

“…By applying the estimated rates of mouse and human neutral evolution (2.2 ϫ 10 Ϫ9 and 4.5 ϫ 10 Ϫ9 substitutions per site per year, respectively) as conservative lower and upper bounds, we obtained an estimated age of 1.9-3.8 million years. It should be noted that this estimate refers only to the divergence of two pSIVgml insertions (i.e., it does not necessarily reflect the age of the pSIVgml germ line invasion, or the extent of the lemurlentivirus association) and is sensitive to the effects of gene conversion and recombination (19,20), which could confound the calculation.…”

Reconstitution of the Ancestral Glycoprotein of Human Endogenous Retrovirus K and Modulation of Its Functional Activity by Truncation of the Cytoplasmic Domain

“…The young age of the 11 proviruses used for alignment makes it very unlikely that the shared polymorphisms are the result of matching postinsertional mutations in more than two individual proviruses or of ectopic recombination events (30) between the env genes of HERV-K113 and two or more of the other aligned elements, although these cannot be completely ruled out.…”

The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

“…Also, as discussed below, HIV-1 integration provides a means of persistence and access to host genetic material that can influence recombination outcomes. Although very infrequent, host-mediated recombination among integrated retroviruses and related elements can also occur and can contribute to host evolution (18,122,140).…”