Similarity in Recombination Rate Estimates Highly Correlates with Genetic Differentiation in Humans

Laayouni H, Montanucci L, Sikora M, Melé M, Dall'Olio GM, et al. (2011) Similarity in Recombination Rate Estimates Highly Correlates with Genetic Differentiation in Humans. PLoS ONE 6(3): e17913. doi:10.1371/journal.pone.0017913

Recombination varies greatly among species, as illustrated by the poor conservation of the recombination landscape between humans and chimpanzees. Thus, shorter evolutionary time frames are needed to understand the evolution of recombination. Here, we analyze its recent evolution in humans. We calculated the recombination rates between adjacent pairs of 636,933 common single-nucleotide polymorphism loci in 28 worldwide human populations and analyzed them in relation to genetic distances between populations. We found a strong and highly significant correlation between similarity in the recombination rates corrected for effective population size and genetic differentiation between populations. This correlation is observed at the genome-wide level, but also for each chromosome and when genetic distances and recombination similarities are calculated independently from different parts of the genome. Moreover, and more relevant, this relationship is robustly maintained when considering presence/absence of recombination hotspots. Simulations show that this correlation cannot be explained by biases in the inference of recombination rates caused by haplotype sharing among similar populations. This result indicates a rapid pace of evolution of recombination, within the time span of differentiation of modern humans. [. . .]

Taking into account only the common hotspots shared by all populations within a given continental region, the proportion of shared hotspots between continental regions is maximum between Europe and Middle East and North Africa (0.52), Europe and Central South Asia (0.44) and between Middle East and North Africa and Central South Asia (0.41). These values are, as expected, much lower when considering Sub-Saharan African or East Asian populations (Table 4). An interesting outcome from this analysis is the number of hotspots common to non African human populations compared to Sub-Saharan Africans. The proportion of hotspots shared between these two groups is only 17.4%, which is a small proportion given the recent out of Africa origin of non African population, and also show that the pace of evolution of hotspots is substantial. Figure S3 shows, as an example, patterns of recombination rates for SNPs where a hotspot event was detected in at least one population. Most variation is observed between continental groups while there is a substantial pattern sharing among populations belonging to the same continental group. [. . .]

Recombination rate appears to be a rapidly changing parameter, indicating that the underlying factors shaping the likelihood of a recombination event, such as DNA sequences controlling recombination rate variation, also change. The change is strongly detectable also in terms of presence or absence of recombination hotspots even if at the present stage it is not possible to measure the relative importance between changes in intermediate recombination rates and the appearing or disappearing of recombination hotspots. This is consistent with recent data showing that allelic variants of PRDM zinc fingers are significantly associated with variability in genome hotspots among humans [8]. The results obtained in this work contribute to the growing perception of recombination not as fixed feature of the genome of a species, but as a phenotype with ample genetic variation.