Mitotic exchange in female germline stem cells is the major source of Sex Ratio chromosome recombination in Drosophila pseudoobscura.

Mitotic exchange in female germline stem cells is the major source of Sex Ratio chromosome recombination in Drosophila pseudoobscura.
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DOI:
10.1093/g3journal/jkac264
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发表时间:
2022-12-01
期刊:
G3 (Bethesda, Md.)
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--
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其他
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伪果蝇的性比染色体是自私的X染色体变异,与3个不重叠的倒位有关。在男性生殖系中,性别比染色体扭曲了X和Y染色体的分离(99:1),从而扭曲了后代的性别比。在雌性生殖系中,性比染色体的分离是孟德尔式的(50:50),但非重叠倒置强烈抑制了重组,建立了26 mb的单倍型(占单倍体基因组的20%)。位于非重叠反转之间的罕见交叉事件可以破坏这种单倍型,并且有时在自然种群中发现重组。我们最近报道了第一个实验室生成的性别比例重组,每个女性减数分裂发生0.0012次交叉。本文提出的改进实验设计表明,这些重组事件的频率至少是先前估计的4倍。此外,重组事件强烈聚集,表明大多数来自雌性种系干细胞的有丝分裂交换,而不是来自原代卵母细胞的减数分裂交叉。最后,互补重组的不对称恢复与不平等交换导致重组诱导的活力缺陷是一致的。将这些实验结果结合到性别比染色体进化的种群模型中,可以更好地适应自然种群频率,并允许维持高度分化的26-Mb性别比单倍型,而无需进行强上位选择。本研究首次估计了果蝇雌性生殖系干细胞中自然发生的染色体自发有丝分裂交换,揭示了更高的性比染色体重组率,并建立了一个准确预测自然群体中重组性比染色体罕见度的数学模型。
Sex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with 3 nonoverlapping inversions. In the male germline, Sex Ratio chromosomes distort the segregation of X and Y chromosomes (99:1), thereby skewing progeny sex ratio. In the female germline, segregation of Sex Ratio chromosomes is mendelian (50:50), but nonoverlapping inversions strongly suppress recombination establishing a 26-Mb haplotype (constituting ∼20% of the haploid genome). Rare crossover events located between nonoverlapping inversions can disrupt this haplotype, and recombinants have sometimes been found in natural populations. We recently reported on the first lab-generated Sex Ratio recombinants occurring at a rate of 0.0012 crossovers per female meiosis. An improved experimental design presented here reveals that these recombination events were at least 4 times more frequent than previously estimated. Furthermore, recombination events were strongly clustered, indicating that the majority arose from mitotic exchange in female germline stem cells and not from meiotic crossing-over in primary oocytes. Finally, asymmetric recovery of complementary recombinants was consistent with unequal exchange causing the recombination-induced viability defects. Incorporating these experimental results into population models for Sex Ratio chromosome evolution provided a substantially better fit to natural population frequencies and allowed maintenance of the highly differentiated 26-Mb Sex Ratio haplotype without invoking strong epistatic selection. This study provides the first estimate of spontaneous mitotic exchange for naturally occurring chromosomes in Drosophila female germline stem cells, reveals a much higher Sex Ratio chromosome recombination rate, and develops a mathematical model that accurately predicts the rarity of recombinant Sex Ratio chromosomes in natural populations.
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