Local and sex-specific biases in crossover vs. noncrossover outcomes at meiotic recombination hotspots in mouse

Abstract

Meiotic recombination initiated by programmed double-strand breaks (DSBs) yields two types of interhomolog recombination products, crossovers and noncrossovers, but what determines whether a DSB will yield a crossover or noncrossover is not understood. In this study we analyze the influence of sex and chromosomal location on mammalian recombination outcomes by constructing fine-scale recombination maps in both males and females at two mouse hotspots located in different regions of the same chromosome. These include the most comprehensive maps of recombination hotspots in oocytes to date. One hotspot, located centrally on chromosome 1, behaved similarly in male and female meiosis: crossovers and noncrossovers formed at comparable levels and ratios in both sexes. In contrast, at a distal hotspot crossovers were recovered only in males even though noncrossovers were obtained at similar frequencies in both sexes. These findings reveal an example of extreme sex-specific bias in recombination outcome. We further find that estimates of relative DSB levels are surprisingly poor predictors of relative crossover frequencies between hotspots in males. Our results demonstrate that the outcome of mammalian meiotic recombination can be biased, that this bias can vary depending on location and cellular context, and that DSB frequency is not the only determinant of crossover frequency.