Why Do Recombination Hotspots Exist

Our lack of understanding of recombination rate heterogeneity in the human genome is emphasised by our ignorance as to why recombination hotspots exist in the first place. Recombination rate heterogeneity seems to be a general feature of sexually reproducing eukaryotic

Fig. 3. The effect of concerted evolution on phylogeny. Independent gene conversion events between paralogous sequences in two sequences lead to the sequences being homogenized within a species. As a consequence, phylogenies constructed from these sequences exhibit a different topology from that expected given the sequence of duplication and speciation events. This phylogenetic pattern can be used to detect regions of the genome undergoing "concerted evolution." The "true phylogeny" shows the actual evolutionary relationships among the four sequence as a result of duplication preceding specia-tion. The "apparent phylogeny" is the phylogeny that would be reconstructed from an alignment of the four sequences after undergoing concerted evolution.

Fig. 3. The effect of concerted evolution on phylogeny. Independent gene conversion events between paralogous sequences in two sequences lead to the sequences being homogenized within a species. As a consequence, phylogenies constructed from these sequences exhibit a different topology from that expected given the sequence of duplication and speciation events. This phylogenetic pattern can be used to detect regions of the genome undergoing "concerted evolution." The "true phylogeny" shows the actual evolutionary relationships among the four sequence as a result of duplication preceding specia-tion. The "apparent phylogeny" is the phylogeny that would be reconstructed from an alignment of the four sequences after undergoing concerted evolution.

species. Are AHR hotspots themselves of benefit to such organisms or are they a by-product of the need to regulate recombination events to ensure correct segregation of chromosomes? There are a number of plausible evolutionary scenarios that explain why hotspots themselves might be beneficial. For example: AHR hotspots might ensure that advantageous linkage groups are maintained together, or they might facilitate the operation of selection by ensuring that selective pressures operate independently at two loci under selection on either side of a hotspot (42). It is less easy to find reasons to explain why NAHR hotspots might exist, other than the fact that they are related mechanistically to AHR hotspots.

One intriguing prospect is that if NAHR and AHR hotspots are linked by a common mechanism, then the two processes are likely to co-evolve. Given the often pathogenic nature of NAHR, it could be that the machinery of AHR evolved to minimize NAHR. This certainly seems possible. Although individual pathogenic NAHR-promoted rearrangements are so rare that locus-specific selective pressures are likely to be too weak to affect evolutionary change, cumulatively these rearrangements may well assert an appreciable selective pressure. Is there any evidence that AHR has evolved to minimize NAHR? In a hypothetical 3-Gb genome comprised of only single copy sequences, the minimal length of sequence identity between recombining partners required to ensure that HR occurs between allelic sequences needs only be approx 20-bp long (frequency of random reoccurrence of a 20mer is 420, which is much more than 3 Gb). This length is at least an order of magnitude shorter than the apparent minimal length in mammals, which seems likely to be more than 200 bp (43). This could well reflect the presence of so many dispersed repeats (and, hence, potential for NAHR) in the human genome. It is also possible that the lower rate of AHR in males reflects enhancement of NAHR on the sex chromosomes in the heterogametic germline, where a lack of meiotic pairing partner outside of the pseudo-autosomal regions may facilitate pathogenic intrachromosomal rearrangements (44). An additional possibility to take into account when extrapolating from studies dissecting HR processes in model organisms is that the apparently recent proliferation of segmental duplications in primate genomes (45) may have imposed further modification on AHR processes, such that significant differences exist between AHR in primates and in other, less-duplicated, mammalian genomes.

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