Crossover interference in D. santomea.

Crossing over is a fundamental process in sexually reproducing species, ensuring proper chromosome segregation during gamete formation and generating new allelic combinations that enhance adaptation. Despite its essential role, genes involved in crossing over evolve rapidly and there is extensive variation in the rate and genomic distribution of crossovers across species. Considering this rapid evolution, identifying differences between very closely related species is crucial for understanding the molecular basis of natural variation in crossing over control. Here, we present a genome-wide, high-resolution crossover map for Drosophila santomea and compare it with those of its sister species D. yakuba and the more distantly related D. melanogaster. Upon examining 784 individual meiotic products based on an experimental design that captures intraspecific variation in crossing over control, we identified 2,288 crossovers genome-wide. Our analyses reveal striking differences in crossover patterns between D. santomea and D. yakuba despite their recent split only 400,000 years ago and sharing a significant amount of ancestral polymorphism. The D. santomea X chromosome shows a major reduction in genetic length compared to D. yakuba (62.7 cM vs. 93.8 cM), while autosomes show a slight increase (262.6 vs. 245.6 cM), resulting in overall genetic maps of 324.2 cM for D. santomea and 339.3 cM for D. yakuba. All D. santomea autosomal arms show a significant reduction of the centromere effect relative to D. yakuba, more closely resembling D. melanogaster autosomes. At the same time, estimates of crossover interference indicate weaker intensity across all autosomal arms in D. santomea compared to D. yakuba, while the X chromosome exhibits considerably stronger interference. These findings suggest a link between the intensity of crossover interference and the centromere effect. We propose that stronger crossover interference is associated with a smaller crossover-competent region—determined by the combined centromere and telomere effects—to prevent the deleterious consequences of multiple crossovers occurring too close together. Finally, we examined whether the D. santomea X chromosome exhibits the crossover-associated meiotic drive mechanism (MDCO) reported in D. yakuba, in which chromatids with crossovers are preferentially included in oocytes. Tetrad analysis of the D. santomea X chromosome revealed no evidence of an active MDCO, potentially explaining the reduced crossover rates observed on this chromosome relative to D. yakuba even though the numbers of meiosis I crossovers may be similar in both species.交叉互换（crossing over）是有性生殖物种的核心生物学过程，既能保障配子形成阶段染色体的精准分离，又能通过产生全新的等位基因组合提升物种的环境适应性。尽管该过程功能不可或缺，但参与交叉互换的基因演化速率极快，且不同物种间的交叉互换（crossover）速率与基因组分布存在广泛差异。鉴于其快速演化的特性，鉴定亲缘关系极近的物种间的差异，对解析交叉互换调控自然变异的分子基础具有关键意义。 本研究构建了圣多美果蝇（Drosophila santomea）的全基因组高分辨率交叉互换图谱（crossover map），并将其与近缘物种雅库巴果蝇（D. yakuba）以及亲缘关系更远的黑腹果蝇（D. melanogaster）的交叉互换图谱进行了比对分析。本研究基于可捕捉交叉互换调控种内变异的实验设计，对784个单个减数分裂产物进行了检测，最终在全基因组范围内鉴定出2288个交叉互换事件。 分析结果显示，尽管圣多美果蝇与雅库巴果蝇仅在40万年前发生分化，且共享大量祖先多态性，但二者的交叉互换模式存在显著差异。与雅库巴果蝇相比，圣多美果蝇的X染色体遗传长度大幅缩短（62.7 cM 对比 93.8 cM），而常染色体则略有增加（262.6 cM 对比 245.6 cM），最终圣多美果蝇的全基因组遗传图谱总长为324.2 cM，雅库巴果蝇则为339.3 cM。相较于雅库巴果蝇，圣多美果蝇的所有常染色体臂均表现出着丝粒效应（centromere effect）的显著减弱，其特征更接近黑腹果蝇的常染色体。与此同时，交叉互换干涉（crossover interference）的评估结果显示，圣多美果蝇所有常染色体臂的干涉强度均弱于雅库巴果蝇，但X染色体的干涉强度则显著更强。上述发现提示交叉互换干涉强度与着丝粒效应之间存在关联。 我们提出，更强的交叉互换干涉与更小的交叉互换易感区域相关——该区域由着丝粒与端粒效应共同决定——以此避免多个交叉互换事件过于邻近而产生有害后果。此外，本研究还验证了圣多美果蝇X染色体是否存在雅库巴果蝇中报道的、与交叉互换相关的减数分裂驱动机制（crossover-associated meiotic drive mechanism, MDCO）：该机制指带有交叉互换的染色单体会优先进入卵母细胞。对圣多美果蝇X染色体的四分体分析（tetrad analysis）未发现活跃MDCO的证据，这或许可以解释：尽管二者的I期减数分裂交叉互换数量可能相近，但圣多美果蝇X染色体的交叉互换速率仍低于雅库巴果蝇。