Article,
Live Hot, Die Young: Transmission Distortion in Recombination Hotspots
PLoS Genet, 3 (3): e35 (March 2007)
DOI: 10.1371/journal.pgen.0030035
Abstract
Recombination is a fundamental component of mammalian meiosis, required to help ensure that daughter cells receive the correct complement of chromosomes. This is highly important, as incorrect segregation causes miscarriage and disorders such as Down syndrome. In addition to its mechanistic function, recombination is also crucial in generating the genetic diversity on which natural selection acts. In humans and many other species, recombination events cluster into narrow hotspots within the genome. Given the vital role recombination plays in meiosis, we might expect that the positions of these hotspots would be tightly conserved over evolutionary time. However, there is now considerable evidence to the contrary; hotspots are not frozen in place, but instead evolve rapidly. For example, humans and chimpanzees do not share hotspot locations, despite their genomic sequences being almost 99% identical. The explanation for this may be, remarkably, that hotspots are the architects of their own destruction. The biological mechanism of recombination dooms them to rapid extinction by favoring the spread of hotspot-disrupting mutations. By mathematically modeling human hotspot evolution, we find that this mechanism can account for fast hotspot turnover, and in fact makes it very difficult for active hotspots to arise at all. Given that active hotspots do exist in our genome, newly arising hotspots must somehow be able to bypass their self-destructive tendency. Despite their importance, it is difficult to identify mutations that disrupt hotspots, as they hide their tracks in genetic data.
