Effects of a male meiotic driver on male and female transcriptomes in the house mouse. Effects of a male meiotic driver on male and female transcriptomes in the house mouse

We investigated effects of the t haplotype in house mice, an autosomal male meiotic driver, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult sibling pairs differing in genotype, allowing us to identify t-associated differences in gene regulation. In testis, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising the t haplotype. Thus much of the activity of the t haplotype occurs in trans, and as up-regulation. Sperm maturation functions were enriched among both cis and trans acting t haplotype genes. Within the t haplotype, more down-regulation and differential exon usage was observed. In ovaries, liver, and brain, the majority of expression differences mapped to the t haplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome. Overall design: We compared the transcriptomes of gonads, liver and brain of male and female siblings pairs (one of the genotype +/t, the other +/+) of house mice reared in the lab until sexual maturity, using RNA-seq. These are wild house mice (Mus musculus domesticus) descended from animals wild-caught from an intensively studied free-living population in Illnau, Switzerland [PMID: 23762510]

本研究以家鼠的t单倍型（t haplotype）——一种常染色体雄性减数分裂驱动因子——为研究对象，探究其对雌雄个体全基因组基因表达模式的影响。我们对基因型存在差异的成年同窝个体的性腺、肝脏与脑组织进行了转录组分析，以此鉴定与t单倍型相关的基因调控差异。在睾丸组织中，仅有40%的差异表达基因（differentially expressed genes）比对至构成t单倍型的约708个注释基因。由此可见，t单倍型的大部分调控活性以反式（trans）方式发挥作用，且表现为基因上调。精子成熟功能在顺式（cis）与反式（trans）作用的t单倍型相关基因中均显著富集。在t单倍型内部，观察到更多的基因下调与外显子差异使用现象。在卵巢、肝脏与脑组织中，大部分表达差异均比对至t单倍型，且与睾丸中观察到的表达差异基本相互独立。总体而言，本研究发现该雄性减数分裂驱动因子在家鼠基因组中存在广泛的转录调控效应。

实验整体设计：本研究采用RNA测序（RNA-seq）技术，对实验室饲养至性成熟的家鼠同窝雌雄个体的性腺、肝脏与脑组织转录组进行比较分析——这些个体的基因型分别为+/t与+/+。实验所用野生家鼠（Mus musculus domesticus）源自瑞士伊尔瑙（Illnau）一处被深入研究的自由生活野生种群的捕获个体[PMID: 23762510]