We built on our earlier work with @jackkamm and @chanjeffreyd to develop a method that could account for demographic history while inferring fine-scale recombination rates.
Method:https://github.com/popgenmethods/pyrho …
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Earlier work showed that failing to account for demographic history can bias recombination rate inference, which is problematic when trying to compare recombination landscapes across populations or species with different historieshttp://dx.doi.org/10.1534/genetics.115.184820 …
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We applied our method to each of the 26 populations in phase 3 of the 1000 Genomes project (to both h19/GRCh37 and hg38/GRCh38). The population-specific recombination maps are available here: https://drive.google.com/open?id=1Tgt_7GsDO0-o02vcYSfwqHFd3JNF6R06 …
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Looking at the recombination maps we found some interesting bits -- the correlations between the maps are generally reflective of what we know about population history, and also reflect the global distribution of different PRDM9 alleles.
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PRDM9 is a protein that positions recombination hotspots, and the C allele of PRDM9 is present at appreciable frequencies only in African populations. Correspondingly we find increased recombination rates at PRDM9-C binding sites only in those populations.
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There's also an interesting story that the double strand breaks involved in recombination events are repaired via homology directed repair, which should cause mutations that disrupt a PRDM9 binding site to increase in frequency.
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We found some evidence of this, but the effect was much weaker than we had originally expected. Some of this might be because we used binding motifs instead of known PRDM9 binding sites, but there are also a lot of hotspots and not very many recombinations per generation.
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The last thing we looked at was whether there are other determinants of recombination rate beyond PRDM9, and we found that chromatin structure appears to modulate recombination rates by about an order of magnitude, but the effect doesn't line up with "open" vs. "closed" chromatin
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In particular, chromatin states characterized by H3K27me3 have particularly elevated recombination rates, and the mechanism for that is not clear. In any case, it's clear there is much more to the story than just PRDM9 binding.
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Fine-scale recombination rates are complex traits, likely influenced by many cis and trans factors.
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