Raw qPCR data plotted in Fig 4B.

Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms that can suppress their activity. Here, we present data from the fruitfly Drosophila simulans that address these questions. We show that a family of de novo, protamine-derived X-linked selfish genes (the Dox gene family) is silenced by a pair of newly emerged hairpin RNA (hpRNA) small interfering RNA (siRNA)-class loci, Nmy and Tmy. In the w[XD1] genetic background, knockout of nmy derepresses Dox and MDox in testes and depletes male progeny, whereas knockout of tmy causes misexpression of PDox genes and renders males sterile. Importantly, genetic interactions between nmy and tmy mutant alleles reveal that Tmy also specifically maintains male progeny for normal sex ratio. We show the Dox loci are functionally polymorphic within D. simulans, such that both nmy-associated sex ratio bias and tmy-associated sterility can be rescued by wild-type X chromosomes bearing natural deletions in different Dox family genes. Finally, using tagged transgenes of Dox and PDox2, we provide the first experimental evidence Dox family genes encode proteins that are strongly derepressed in cognate hpRNA mutants. Altogether, these studies support a model in which protamine-derived drivers and hpRNA suppressors drive repeated cycles of sex chromosome conflict and resolution that shape genome evolution and the genetic control of male gametogenesis.减数分裂驱动位点（meiotic drive loci）会扭曲等位基因（alleles）原本均等的分离比例，即便会对宿主生物体造成严重的适合度代价（fitness costs），仍能提升自身的传递效率。然而，目前学界对减数分裂驱动因子的分子本质、作用策略以及抑制其活性的机制仍知之甚少。本研究基于拟果蝇（Drosophila simulans）的相关数据解答了上述问题。我们发现，一类从头起源、源自鱼精蛋白（protamine）的X连锁（X-linked）自私基因（selfish genes）家族（即Dox基因家族），可被一对新演化出的发夹RNA（hairpin RNA, hpRNA）小干扰RNA（small interfering RNA, siRNA）类位点Nmy与Tmy所沉默。在w[XD1]遗传背景下，基因敲除（knockout）nmy会使睾丸（testes）中的Dox与MDox基因去抑制，并导致雄性后代（male progeny）数量锐减；而敲除tmy则会引发PDox基因的异常表达，并导致雄性不育。值得注意的是，nmy与tmy突变等位基因（mutant alleles）间的遗传互作（genetic interactions）分析显示，Tmy还可特异性地维持雄性后代数量以保障正常的性比（sex ratio）。我们还发现，Dox位点在拟果蝇（Drosophila simulans）中存在功能多态性：携带不同Dox家族基因自然缺失的野生型（wild-type）X染色体（chromosomes），可分别挽救nmy突变引发的性比偏离与tmy突变导致的不育表型。最后，通过Dox与PDox2的标签转基因（tagged transgenes）实验，我们首次提供实验证据表明：Dox家族基因编码的蛋白质（proteins）在同源（cognate）hpRNA突变体中会被显著去抑制。综上，本研究支持如下模型：源自鱼精蛋白的驱动因子与hpRNA抑制因子，通过反复引发性染色体冲突（sex chromosome conflict）与修复循环，塑造了基因组演化（genome evolution）与雄性配子发生（male gametogenesis）的遗传调控机制。