Heterozygous inversion breakpoints suppress meiotic crossovers by altering recombination repair outcomes

Abstract

Heterozygous chromosome inversions suppress meiotic crossover (CO) formation within an inversion, potentially because they lead to gross chromosome rearrangements that produce inviable gametes. Interestingly, COs are also severely reduced in regions nearby but outside of inversion breakpoints even though COs in these regions do not result in rearrangements. Our mechanistic understanding of why COs are suppressed outside of inversion breakpoints is limited by a lack of data on the frequency of noncrossover gene conversions (NCOGCs) in these regions. To address this critical gap, we mapped the location and frequency of rare CO and NCOGC events that occurred outside of the dl-49 chrX inversion in D. melanogaster. We created full-sibling wildtype and inversion stocks and recovered COs and NCOGCs in the syntenic regions of both stocks, allowing us to directly compare rates and distributions of recombination events. We show that COs outside of the proximal inversion breakpoint are distributed in a distance-dependent manner, with strongest suppression near the inversion breakpoint. We find that NCOGCs occur evenly throughout the chromosome and, importantly, are not suppressed near inversion breakpoints. We propose a model in which COs are suppressed by inversion breakpoints in a distance-dependent manner through mechanisms that influence DNA double-strand break repair outcome but not double-strand break formation. We suggest that subtle changes in the synaptonemal complex and chromosome pairing might lead to unstable interhomolog interactions during recombination that permits NCOGC formation but not CO formation.

Complex genomic landscape of inversion polymorphism in Europe’s most destructive forest pest

“…In addition, genomics scans for selection in inversion-rich genomes may be biased due to reduced recombination within inversion regions. Importantly, the effect of reduced recombination may extend outside inversions (Adrion et al 2020; Koury 2023; Li et al 2023). The influence of inversions and inversion-rich genomes on various evolutionary inference methods may become a standard scenario to test their robustness (Novo et al 2023).…”

The effects of inversion polymorphisms on patterns of neutral genetic diversity

“…This raises the question of whether recombinational exchange in heterokaryotypes occurs at a sufficient rate that the condition T Sw = 1 is likely to hold. At least for simple inversions (with only a single pair of breakpoints), there is ample experimental evidence for recombination between In and St at sites within and adjacent to the inversion in species of Drosophila , much of which appears to be caused by gene conversion rather than double crossovers ( Chovnick 1973 ; Korunes and Noor 2019 ; Koury 2023 ; Li et al . 2023 ), with r = 10 –5 per base pair per generation in female meiosis being a commonly accepted typical rate for central regions of inversions ( Chovnick 1973 ; Korunes and Noor 2019 ); for autosomal loci, the lack of recombination in males means that the effective r is half of this value.…”

“… Rozas et al . (1999) obtained population genetic evidence for gene conversion events near the breakpoints of arrangements in the O chromosome system of inversions in D. subobscura , and Li et al . (2023) found no evidence for an effect of proximity to breakpoints for the dl-49 inversion of D. melanogaster on the rate of gene conversion.…”

“…It is likely that the value of r will depend on the location of the site within the inversion, with the largest values for sites within the inversion that are remote from the breakpoints, due to the effects of the breakpoints in disturbing synapsis ( Navarro et al . 1997 ), although the extent to which gene conversion events are influenced by proximity to the breakpoints is uncertain ( Li et al . 2023 ).…”

“…Recent studies of heterozygous Drosophila inversions suggest a near-total suppression of crossing over within the regions covered by a heterozygous inversion and for a substantial distance outside it ( Koury 2023 ; Li et al . 2023 ).…”