Museum of Vertebrate Zoology and Department of Integrative Biology, University of California, Berkeley, Berkeley, California, United States of America.
PLoS Genet. 2024 Feb 2;20(2):e1010892. doi: 10.1371/journal.pgen.1010892. eCollection 2024 Feb.
Changes in gene regulation have long been appreciated as a driving force of adaptive evolution, however the relative contributions of cis- and trans-acting changes to gene regulation over short evolutionary timescales remain unclear. Instances of recent, parallel phenotypic evolution provide an opportunity to assess whether parallel patterns are seen at the level of gene expression, and to assess the relative contribution of cis- and trans- changes to gene regulation in the early stages of divergence. Here, we studied gene expression in liver and brown adipose tissue in two wild-derived strains of house mice that independently adapted to cold, northern environments, and we compared them to a strain of house mice from a warm, tropical environment. To investigate gene regulatory evolution, we studied expression in parents and allele-specific expression in F1 hybrids of crosses between warm-adapted and cold-adapted strains. First, we found that the different cold-adapted mice showed both unique and shared changes in expression, but that the proportion of shared changes (i.e. parallelism) was greater than expected by chance. Second, we discovered that expression evolution occurred largely at tissue-specific and cis-regulated genes, and that these genes were over-represented in parallel cases of evolution. Finally, we integrated the expression data with scans for selection in natural populations and found substantial parallelism in the two northern populations for genes under selection. Furthermore, selection outliers were associated with cis-regulated genes more than expected by chance; cis-regulated genes under selection influenced phenotypes such as body size, immune functioning, and activity level. These results demonstrate that parallel patterns of gene expression in mice that have independently adapted to cold environments are driven largely by tissue-specific and cis-regulatory changes, providing insight into the mechanisms of adaptive gene regulatory evolution at the earliest stages of divergence.
基因调控的变化长期以来一直被认为是适应性进化的驱动力，然而，在短时间尺度上，顺式和反式作用变化对基因调控的相对贡献仍不清楚。最近的平行表型进化实例为评估在基因表达水平上是否存在平行模式提供了机会，并评估在分化的早期阶段顺式和反式变化对基因调控的相对贡献。在这里，我们研究了两个独立适应寒冷北方环境的野生家鼠品系的肝脏和棕色脂肪组织中的基因表达，并将它们与来自温暖热带环境的家鼠品系进行了比较。为了研究基因调控进化，我们研究了杂交 F1 代中适应温暖和适应寒冷的亲本品系之间的基因表达和等位基因特异性表达。首先，我们发现不同的适应寒冷的小鼠表现出独特的和共同的表达变化，但共同变化的比例（即平行性）超出了随机预期。其次，我们发现表达进化主要发生在组织特异性和顺式调控基因中，并且这些基因在进化的平行案例中被过度代表。最后，我们将表达数据与自然种群中的选择扫描相结合，发现两个北方种群中受选择影响的基因存在大量平行性。此外，选择异常值与顺式调控基因的关联比预期的更频繁；受选择影响的顺式调控基因影响了体型、免疫功能和活动水平等表型。这些结果表明，独立适应寒冷环境的小鼠中基因表达的平行模式主要由组织特异性和顺式调控变化驱动，为分化早期适应性基因调控进化的机制提供了深入了解。
