A major goal of evolutionary genetics is to understand the genetic and molecular mechanisms underlying adaptation. Previous work has established that changes in gene regulation may contribute to adaptive evolution, but most studies have focused on mRNA abundance and only a few studies have investigated the role of post-transcriptional processing. Here, we use a combination of exome sequences and short-read RNA-Seq data from wild house mice (Mus musculus domesticus) collected along a latitudinal transect in eastern North America to identify candidate genes for local adaptation through alternative splicing. First, we identified alternatively spliced transcripts that differ in frequency between mice from the northern-most and southern-most populations in this transect. We then identified the subset of these transcripts that exhibit clinal patterns of variation among all populations in the transect. Finally, we conducted association studies to identify cis-acting splicing quantitative trait loci (cis-sQTL), and we identified cis-sQTL that overlapped with previously ascertained targets of selection from genome scans. Together, these analyses identified a small set of alternatively spliced transcripts that may underlie environmental adaptation in house mice. Many of these genes have known phenotypes associated with body size, a trait that varies clinally in these populations. We observed no overlap between these genes and genes previously identified by changes in mRNA abundance, indicating that alternative splicing and changes in mRNA abundance may provide separate molecular mechanisms of adaptation.

进化遗传学的一个主要目标是了解适应背后的遗传和分子机制。先前的工作已经证实基因调控的变化可能有助于适应性进化，但大多数研究都集中在 mRNA 丰度上，只有少数研究调查了转录后加工的作用。在这里，我们结合外显子组序列和来自北美东部纬度横断面收集的野生家鼠（Mus musculus Domesticus ）的短读长RNA-Seq数据，来识别通过选择性剪接进行局部适应的候选基因。首先，我们鉴定了来自该横断面最北端和最南端群体的小鼠之间频率不同的选择性剪接转录本。然后，我们鉴定了这些转录物的子集，这些转录物在样带中的所有种群中表现出临床变异模式。最后，我们进行了关联研究来鉴定顺式作用剪接数量性状位点（cis -sQTL），并且我们鉴定了与之前从基因组扫描中确定的选择目标重叠的顺式 -sQTL 。总之，这些分析确定了一小部分选择性剪接的转录本，它们可能是家鼠环境适应的基础。其中许多基因具有与体型相关的已知表型，这种特征在这些人群中存在临床差异。我们观察到这些基因和之前通过 mRNA 丰度变化识别的基因之间没有重叠，这表明选择性剪接和 mRNA 丰度的变化可能提供单独的适应分子机制。