Cell numbers.

Sex-linked meiotic drivers limit the inheritance of the alternate sex chromosome in the heterogametic sex, subsequently skewing the offspring sex ratio. They consequently have large impacts on genome evolution, adaptation, and the emergence and maintenance of sexually selected traits. Despite this, our understanding of their molecular basis and consequences for gametogenesis and sex chromosome regulation more broadly has focused on a handful of model organisms, primarily Drosophila and mouse, which are not representative of the broad diversity of reproductive modes and drive systems in nature. Here, we employ single-cell RNA sequencing (scRNA-seq) to investigate a sex-linked meiotic driver in the Malaysian stalk-eyed fly, Teleopsis dalmanni. First, we produce a comprehensive single-cell atlas of the male T. dalmanni gonad and identify major testis cell types. We then provide a comprehensive profile of the cellular and transcriptional landscape of the testis, providing evidence for a lack of complete meiotic sex chromosome inactivation and complex trajectory of dosage compensation. Second, by contrasting single-cell expression data between drive and standard testes, we provide insight into the consequences of a meiotic driver for the transcriptomic landscape of the testis and sex chromosome regulation. Importantly, we show that the presence of a meiotic driver does not perturb fundamental patterns of X-linked regulation. Our results provide insight into how the meiotic driver might bias its transmission to the next generation and highlight genes with perturbed expression as a potential consequence of the disruption of spermatogenesis.

性连锁减数分裂驱动因子（sex-linked meiotic driver）可限制异配性别（heterogametic sex）中异型性染色体（alternate sex chromosome）的传递，进而使后代性别比例发生偏倚。因此，这类驱动因子对基因组进化、适应性演化以及性选择性状的起源与维持均具有深远影响。尽管如此，目前学界对这类驱动因子的分子机制，以及其对配子发生乃至更广范畴内性染色体调控的影响的认知，仍仅局限于少数模式生物，主要为果蝇（Drosophila）与小鼠（mouse），但这些模式生物并不能代表自然界中生殖方式与驱动系统的广泛多样性。本研究借助单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，针对马来西亚柄眼蝇（Teleopsis dalmanni）体内的性连锁减数分裂驱动因子开展研究。首先，我们构建了雄性马来西亚柄眼蝇生殖腺的完整单细胞图谱，并鉴定出睾丸的主要细胞类群；随后，我们全面解析了睾丸的细胞与转录组全景，为该物种未发生完全的减数分裂性染色体失活（meiotic sex chromosome inactivation），且剂量补偿（dosage compensation）过程存在复杂动态轨迹提供了实验证据。其次，我们通过对比携带驱动因子与标准型睾丸的单细胞表达数据，解析了减数分裂驱动因子对睾丸转录组全景以及性染色体调控的影响。尤为关键的是，本研究证实减数分裂驱动因子的存在并不会扰乱X连锁调控的基本模式。本研究结果揭示了减数分裂驱动因子可能通过何种途径实现偏向性传递，并筛选出表达异常的基因，这些基因或为精子发生（spermatogenesis）受阻的潜在效应产物。