Absence of the TAP2 human recombination hotspot in chimpanzees - PubMed (original) (raw)

Comparative Study

Absence of the TAP2 human recombination hotspot in chimpanzees

Susan E Ptak et al. PLoS Biol. 2004 Jun.

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.

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Conflict of interest statement

The authors have declared that no conflicts of interest exist.

Figures

Figure 1

Figure 1. Patterns of Pairwise LD in Humans and Chimpanzees

Only SNPs with minor allele frequencies above 0.1 are included. The rows correspond to the consecutive SNPs in the region, as do the columns. Each cell indicates the extent of LD between a pair of sites, as measured by |_D_′| (estimated using the Expectation Maximization algorithm, as implemented by Arlequin:

http://lgb.unige.ch/arlequin/

).

Figure 2

Figure 2. Estimates of the Recombination Hotspot Intensity, λ, Based on Genotype Data

We assumed that, if the hotspot is present, it is in the same location as estimated by sperm typing in humans (see Materials and Methods). A λ value of one corresponds to the absence of recombination rate variation, while values of λ greater than one indicate a hotspot. The estimates for humans from the UK are shown in blue and those for western chimpanzees in orange.

Figure 3

Figure 3. Estimates of Recombination Rate Variation in Humans and Western Chimpanzees

In this model, there is at most one hotspot in the region, the location and width of which are unknown and estimated along with λ and ρ. On the _y_-axis is an estimate of the posterior probability of elevated recombination, Pr(λ > 1), between each pair of consecutive SNPs (plotted at the midpoint position).

Figure 4

Figure 4. Distribution of Variable Sites in the Genomic Region

The positions of sites that differ between humans and chimpanzees are shown on the first line, while the positions of sites polymorphic in humans from the UK or in western chimpanzees are shown on the next two lines. The human hotspot region is underlined. The dashed lines indicate regions not surveyed for variation in western chimpanzees (see Materials and Methods).

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