Speculatively, first-order rate kinetics could provide the primary force for retention (and commensurate repositioning) of DNA sequence-regulated hotspots over evolutionary timescales.
As DNA sequence-regulated hotspots arise de novo in the genome via mutation (a stochastic process), differential selective pressures would subsequently drive their localization away from coding regions and hence toward IGRs and introns.
There is also some evidence that microsatellites could have a role in regulating hotspot recombination [ 11- 14], increasing the relevance of studying their association with hotspots, since the basis in sequence of the control of hotspot locations is not yet well understood [ 42- 44, 46- 48].
There are now at least 10 different DNA sequence motifs demonstrated by base-pair mutagenesis (5 in fission yeast), implicated by deletion studies (3 in budding yeast), or inferred from association studies (1 class each in humans and mice) to regulate hotspot activity (Schuchert et al. 1991; White et al. 1993; Myers et al. 2008; Steiner et al. 2009; Baudat et al. 2010).
Thus finding other trans- and cis- regulators that can also regulate recombination hotspots is highly desired.
Furthermore, the function of PRDM9 for regulating recombination hotspots is well conserved among human, chimpanzee and mouse [ 3],[ 4].
Recently, a zinc finger protein PRDM9 was reported to regulate recombination hotspots in human and mouse genomes.
It would be an interesting question in comparative genomics whether there are any other genes or complexes whose functional roles in regulating recombination hotspots are conserved among species.
On the other hand, some "epigenetic" factors may regulate recombination hotspots (Paigen and Petkov 2010; Barthès et al. 2011; Smagulova et al. 2011).
While compelling, it remains to be experimentally determined if such polymorphic antigen genes are indeed regulated by eQTL hotspots we identified in the same region.
Large-scale experimental studies in yeast could be used to quantify the level of influence hotspots have on microsatellite evolution, and to explore the possible functional role of microsatellites in regulating recombination.
