Different recombination hotspots in humans and chimpanzees

Winckler et al. (2005) (Science online) surveyed sequence data from humans and chimpanzees to examine whether recombination was happening at similar rates in both species. They found that even though the human and chimpanzee sequences were 99 percent identical, recombination hotspots were highly different, and rarely occurred in the same places.

At present it is not known what molecular factors result in recombination at particular genomic locations, so it is unclear what accounts for the difference between humans and chimpanzees in hotspot locations. For this reason, the authors interpret their findings in terms of several possible hypotheses:

The lack of correlation in recombination patterns between humans and chimpanzees demonstrates that fine-scale recombination rates evolve rapidly, to an extent disproportionate to the change in nucleotide sequence. Rapid evolution of hotspots has previously been hypothesized on the basis of examples of meiotic drive at hotspots and the mechanism of DSB repair (9, 12). Our observations argue against models in which hotspots are directed solely by short, neutrally evolving DNA motifs, which would almost always be identical between the two species. Epigenetic factors, which are known to play a role in recombination hotspots (7), may vary more substantially across closely related species than does DNA sequence. Alternatively, if the trans-acting molecular machinery that initiates crossover events has nucleotide site preferences, then it is possible that substitutions in these components could dramatically alter site preference across the genome. Although DNA sequence is typically shared across human and chimpanzee, the polymorphisms in each species are not (26). It is intriguing to speculate that polymorphisms could themselves play a role in shaping fine-scale recombination; this could also explain why different alleles of a given locus can have substantially different recombination rates (9). Finally, we note that if recombination rates evolve rapidly, then in some cases, rates from "historical" polymorphism data might truly differ from contemporaneous rates in sperm (Winckler et al. 2005:110).

To me, the research raises an interesting question: if humans and chimpanzees are so divergent in recombination parameters, shouldn't we expect humans to be fairly different from each other also? On average, human alleles are about a tenth as different from each other in sequence as human alleles are from chimpanzee alleles. If the rate of change between humans and chimpanzees has been high, then human polymorphism should include a substantial recombinational component -- perhaps more significant in magnitude than conventional sequence polymorphism. As the study puts it:

By applying these analytical methods to genome-wide polymorphism surveys, an extensive collection of recombination hotspots will soon be available across the human genome. Studying these hotspots should ultimately illuminate the as yet mysterious factors that direct the location and frequency of recombination in our species (Winckler et al. 2005:110).

I wonder whether these results will ultimately affect our interpretation of diversity within and outside of Africa -- especially in light of the suggestion that human populations within Africa have undergone adaptation to several fairly distinct local environments. If there are recombinational differences that may act as either impediments or facilitators to selection on particular genomic regions, that might influence the dispersal of adaptive genes (or genetic elements). Likewise, although microsatellites are not directly related to mutational hotspots, there are substantial differences between humans and chimpanzees in terms of variable microsatellite loci. In both cases, human variability may ultimately be the result not only of the factors affecting human populations globally, but also the evolution of the systems themselves in terms of some loci becoming more mutationally active or less active in some populations over time. It is an interesting genomic world out there, that we are just beginning to understand.

References:

Winckler W, Myers SR, Richter DJ, Onofrio RC, McDonald GJ, Bontrop DE, McVean GAT, Gabriel SB, Reich D, Donnelly P, Altshuler D. 2005. Comparison of Fine-Scale Recombination Rates in Humans and Chimpanzees. Science 308:107-111.