Evolution of Homologous Recombination Mechanisms

NIH RePORTER · NIH · R01 · $310,215 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Homologous recombination reshuffles genetic information between parental chromosomes generating genetic diversity and driving evolution. Recombination predominantly occurs at recombination hotspots, the narrow genomic regions where recombination frequency exceeds the frequency in the adjacent areas by up to three orders of magnitude. In some species, hotspots localize opportunistically to the regions with open chromatin configuration, such as promoters, enhancers and CpG islands. In others, including humans and mice, hotspots are routed away from these functional elements by the PRDM9 protein, protecting them from mutagenic effects of recombination. Deletion of the Prdm9 gene results in relocation of hotspots from PRDM9 binding sites back to promoters, leading to sterility or subfertility in mice and rats, but seemingly not in humans. This means that recombination-induced mutations in functional genomic elements will be passed to progeny. Furthermore, since locations of recombination hotspots change dramatically in Prdm9 mutants, the established patterns of linkage disequilibrium will be broken, leading to novel allele combinations. Therefore, investigation of the consequences of the Prdm9 loss in species that naturally lost Prdm9 through evolution is of particular interest. In this study we will map recombination hotspots in three species that lost canonical Prdm9 and examine three specific mechanisms that may define recombination landscape in such species.

Key facts

NIH application ID
10370394
Project number
5R01GM114173-06
Recipient
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
Principal Investigator
Galina Petukhova
Activity code
R01
Funding institute
NIH
Fiscal year
2022
Award amount
$310,215
Award type
5
Project period
2015-04-01 → 2025-03-31