Effects of recombination rate on human endogenous retrovirus fixation and persistence

Abstract

Endogenous retroviruses (ERVs) result from germ line infections by exogenous retroviruses. They can proliferate within the genome of their host species until they are either inactivated by mutation or removed by recombinational deletion. ERVs belong to a diverse group of mobile genetic elements collectively termed transposable elements (TEs). Numerous studies have attempted to elucidate the factors determining the genomic distribution and persistence of TEs. Here we show that, within humans, gene density and not recombination rate correlates with fixation of endogenous retroviruses, whereas the local recombination rate determines their persistence in a full-length state. Recombination does not appear to influence fixation either via the ectopic exchange model or by indirect models based on the efficacy of selection. We propose a model linking rates of meiotic recombination to the probability of recombinational deletion to explain the effect of recombination rate on persistence. Chromosomes 19 and Y are exceptions, possessing more elements than other regions, and we suggest this is due to low gene density and elevated rates of human ERV integration in males for chromosome Y and segmental duplication for chromosome 19.

FIG. 1.

(A) Scatterplot showing the density of the total number of HERV integrations (solo-LTRs plus paired LTRs) against gene density. Filled diamonds represent human chromosomes, whereas the open diamond represents the 5-Mb region at 19p12 (note that the chromosome 19 diamond does not include 19p12). The trendline and R² do not include data from chromosomes Y, 19, and 19p12. (B) Scatterplot showing the total fixation density for different host recombination rates. The recombination rate was divided into equally sized bins of 0.1 cM/Mb for values between 0 and 3 cM/Mb, with a single recombination rate bin for values of >3 cM/Mb. The fixation density was calculated by dividing the total number of fixations corresponding to each recombination bin, divided by the total amount of sequenced DNA in that bin. (C) Scatterplot showing the ratio of paired to solo-LTRs against recombination rate. The recombination rate was calculated as in panel B.