# Evolution of Homologous Recombination Mechanisms

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2024 · $65,582

## Abstract

ABSTRACT
Homologous recombination reshuffles genetic information between parental chromosomes generating genetic
diversity and driving evolution. Recombination predominantly occurs at a set of genomic locations called
recombination hotspots. In most mammals, including humans, hotspot locations are defined by the sequence-
specific binding of the PRDM9 protein, which trimethylates lysine 4 of the histone H3 at the sites where
recombination is later initiated. In Prdm9 knockout mice DSBs are targeted to gene promoters and enhancers,
which also carry the H3K4 trimethylation mark. Therefore, PRDM9 directs recombination away from functional
genomic elements. This role is important as data indicate mutagenic effects of recombination both on the local
nucleotide level and in gross chromosomal rearrangements. Nevertheless, some species do not have the
Prdm9 gene or have lost canonical Prdm9 through evolution. In most of such species, recombination hotspots
still exist, but they form at the H3K4me3-marked gene promoters and other genomic regions with accessible
DNA. In contrast, nematodes and dipterans do not have recombination hotspots. Why promoters are not
targeted by the DSB machinery in such species is not understood. Surprisingly, in this study we found that in
marsupial Monodelphis Domestica, hotspots actually avoid promoters, even though they tend to cluster rather
uniformly withing gene bodies. Finding the mechanism driving such an unusual distribution of recombination
events is the current goal of this study. In addition to the prominent role of homologous recombination in
evolution, recombination per se is essential for proper segregation of homologous chromosomes during
gametogenesis. Recombination defects are invariably associated with infertility, miscarriage and aneuploidy-
related birth defects. Defining the mechanisms that control genetic recombination will eventually aid in
detection, prevention and/or treatment of aneuploidy-related infertility and birth defects.

## Key facts

- **NIH application ID:** 11021354
- **Project number:** 3R01GM114173-08S1
- **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:** $65,582
- **Award type:** 3
- **Project period:** 2015-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11021354

## Citation

> US National Institutes of Health, RePORTER application 11021354, Evolution of Homologous Recombination Mechanisms (3R01GM114173-08S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11021354. Licensed CC0.

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