# Evolution of Homologous Recombination Mechanisms

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2024 · $310,215

## 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:** 10808950
- **Project number:** 5R01GM114173-08
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Galina Petukhova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $310,215
- **Award type:** 5
- **Project period:** 2015-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808950

## Citation

> US National Institutes of Health, RePORTER application 10808950, Evolution of Homologous Recombination Mechanisms (5R01GM114173-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10808950. Licensed CC0.

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