Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

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During formation of sperm and eggs chromosomes exchange DNA in a process known as recombination, creating new combinations responsible for much of the enormous diversity in populations. In some mammals, including humans, the locations of recombination are chosen by a DNA-binding protein named PRDM9. Importantly, there are tens to hundreds of different variations of the Prdm9 gene (termed alleles), many of which are predicted to bind a unique DNA sequence. This high frequency of variation results in many individuals having two different copies of Prdm9, and several lines of evidence indicate that alleles compete to initiate recombination. In seeking to understand the mechanism of this competition we found that Prdm9 activity is sensitive to the number of gene copies present, suggesting that availability of this protein is a limiting factor during recombination. Moreover, we found that variant forms of PRDM9 protein can physically interact suggesting that when this happens one variant can influence which hotspots will become activated. Genetic crosses in mice support these observations; the presence of a dominant Prdm9 allele can completely suppress recombination at some locations. We conclude that allele-dominance of PRDM9 is a consequence of protein-protein interaction and competition for DNA binding in a limited pool of molecules, thus shaping the recombination landscape in natural populations.

Vyšlo v časopise: Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005512
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005512

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