Absence of the TAP2 Human Recombination Hotspot in Chimpanzees

Abstract

Recent experiments using sperm typing have demonstrated that, in several regions of the human genome, recombination does not occur uniformly but instead is concentrated in “hotspots” of 1–2 kb. Moreover, the crossover asymmetry observed in a subset of these has led to the suggestion that hotspots may be short-lived on an evolutionary time scale. To test this possibility, we focused on a region known to contain a recombination hotspot in humans, TAP2, and asked whether chimpanzees, the closest living evolutionary relatives of humans, harbor a hotspot in a similar location. Specifically, we used a new statistical approach to estimate recombination rate variation from patterns of linkage disequilibrium in a sample of 24 western chimpanzees (Pan troglodytes verus). This method has been shown to produce reliable results on simulated data and on human data from the TAP2 region. Strikingly, however, it finds very little support for recombination rate variation at TAP2 in the western chimpanzee data. Moreover, simulations suggest that there should be stronger support if there were a hotspot similar to the one characterized in humans. Thus, it appears that the human TAP2 recombination hotspot is not shared by western chimpanzees. These findings demonstrate that fine-scale recombination rates can change between very closely related species and raise the possibility that rates differ among human populations, with important implications for linkage-disequilibrium based association studies.

No effect of recombination on the efficacy of natural selection in primates

“…But the assumption may not be as applicable to the fine scale. Indeed, analyses of LD data in humans and chimpanzees indicate that although rates >50 kb are weakly correlated , hotspot locations differ markedly between the two species (Wall et al 2003;Ptak et al 2004Ptak et al , 2005Winckler et al 2005). If HRI exerts its effects over very short distances, and fine-scale rates have changed markedly between species, some of the signal could be masked as a result.…”

“…At a finer scale, recombination rates may have changed substantially: Although fine-scale rates may be partially conserved Ptak et al 2005), hotspot locations seem to differ markedly between human and chimpanzee (Wall et al 2003;Ptak et al 2004Ptak et al , 2005Winckler et al 2005). Rapid turnover of hotspots could lead human fine-scale rates to be poor proxies for the fine-scale recombination environment for much of the phylogeny.…”

Recombination rate variation in closely related species

“…Three methods are commonly used for estimating recombination rate: linkage disequilibrium (LD) mapping, sperm typing and direct mapping using polymorphic markers (see Table 2 for examples of recombination maps generated with these approaches, and Table 3 for potential strengths and weaknesses). The first two methods are used primarily with human data (but see Guillon and de Massy, 2002;Ptak et al, 2004;Kim et al, 2007;Arguello et al, 2010), with the labor-and resourceintensive direct mapping applied more in other model organisms. Fundamentally, the major differences between these measures are (1) whether the recombination rates measured are current versus historical, and (2) whether the recombination rates measured reflect a population average or focus on a particular individual or set of individuals.…”

Hotspots for copy number variation in chimpanzees and humans

“…Also of evolutionary interest are regions for which CNVs are common in one species but not observed in the other, despite the presence of ancestral segmental duplications. Such patterns may reflect lineagespecific changes in other genomic features (e.g., recent studies have shown that recombination hotspots are not always shared between humans and chimpanzees) (47)(48)(49) or recent selective pressure in one lineage.…”