# Meiotic double-strand DNA breaks and spontaneous mutation in Drosophila melanogaster

## TL;DR

This study in fruit flies shows that meiotic DNA breaks don't significantly affect point mutations but influence transposable element activity and mutation distribution.

## Contribution

The study experimentally links meiotic recombination to transposable element suppression and mutation distribution in a controlled genetic system.

## Key findings

- Meiotic DSBs had little effect on point mutation rates or spectra.
- Mutations occurred more in regions with higher crossover recombination.
- TE insertions increased in the absence of meiotic DSBs.

## Abstract

The exchange of genetic material during meiosis requires the formation and repair of DNA double-strand breaks (DSBs), which may not be repaired with perfect fidelity. If meiotic exchange is mutagenic, this would add to the costs of sexual reproduction and affect patterns of genome evolution, but much of the evidence for this is indirect. In the fruit fly Drosophila melanogaster, it is possible to completely suppress endogenous DSBs while retaining normal fertility. We took advantage of this system to generate fly strains with and without a mutant allele of mei-P22, a gene that is essential for meiotic DSB formation, on a common genetic background. This allowed us to investigate the relationship between DSBs and genome-wide mutation patterns, using a mutation accumulation design to allow unselected spontaneous mutations to be observed. Following 30 generations of mutation accumulation, we identified over 1,800 mutations by whole-genome sequencing. The presence of meiotic DSBs had little effect on the rate and spectrum of point mutations. We found that mutations were more likely to occur in areas of the genome with higher rates of crossover recombination, regardless of whether meiotic DSBs were occurring. We also found that the rate of transposable element insertions across multiple TE families was substantially elevated in the group lacking meiotic DSBs, suggesting that host suppression of mobile genetic elements is closely associated with meiotic recombination mechanisms.