Identifying the molecular mechanisms contributing to phenotypic variation in natural populations is a major goal of molecular ecology. However, the multiple regulatory steps between genotype and phenotype mean that many potential mechanisms can lead to trait divergence. To date, the role of transcriptional regulation in local adaptation has received much focus, as we can readily measure mRNA quantity and have a reasonable grasp of how variation in the expression of many protein-coding genes can influence phenotype. Thus, studying the evolution of protein-coding gene mRNA abundance in candidate tissues has led to successes in detecting the molecular mechanisms underlying local adaptation (reviewed by Hill et al., 2021). However, the contribution of differential splicing of precursor mRNA (pre-mRNA) to adaptive differentiation, as well as the loci controlling this variation, remains largely unexplored in wild populations. In their “From the Cover'” article in this issue of Molecular Ecology, Jacobs and Elmer (2021) reanalyse muscle RNA sequencing (RNA-seq) data to quantify the relative contributions of variation in mRNA quantity (differentially expressed “DE” genes) and splice variant identity (differentially spliced “DS” genes) to parallel divergence of wild “benthic” and “pelagic” ecotypes of a salmonid fish, the Arctic charr (Salvelinus alpinus). They found little overlap in the identity and biological functions of DE and DS genes, suggesting that these two regulatory mechanisms act on different cellular traits to complementarily alter organismal phenotype. Furthermore, many DE and DS genes could be mapped to cis-acting QTL, arguing that some of this regulatory divergence is genetically based. DE and DS genes were also more likely to be “hub genes” than their nondivergent counterparts, hinting that this regulatory variation may have a variety of phenotypic effects. The comparison of three independently evolved pairs of benthic and pelagic charr uncovered greater than expected parallelism in both expression and splicing between ecotypes across different lakes, supporting a role for these molecular phenotypes in adaptive divergence. Overall, the findings of Jacobs and Elmer (2021) highlight the importance of alternative splicing as a potential mechanism underlying local adaptation and provide a framework for others hoping to make the most of their RNA-seq data.

中文翻译：

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选择性剪接：一种被忽视的促进局部适应的机制？

确定导致自然种群表型变异的分子机制是分子生态学的主要目标。然而，基因型和表型之间的多重调控步骤意味着许多潜在的机制会导致性状差异。迄今为止，转录调控在局部适应中的作用受到了很多关注，因为我们可以很容易地测量 mRNA 的数量，并合理掌握许多蛋白质编码基因表达的变化如何影响表型。因此，研究候选组织中蛋白质编码基因 mRNA 丰度的演变已导致成功检测局部适应的分子机制（Hill 等人，2021 年综述）。然而，前体mRNA（pre-mRNA）的差异剪接对适应性分化的贡献，以及控制这种变异的基因座，在野生种群中很大程度上仍未被探索。在本期《分子生态学》的“来自封面”文章中，Jacobs 和 Elmer (2021) 重新分析了肌肉 RNA 测序 (RNA-seq) 数据，以量化 mRNA 数量（差异表达的“DE”基因）变化的相对贡献和剪接变体身份（差异剪接的“DS”基因）与鲑鱼北极鲑鱼的野生“底栖”和“远洋”生态型的平行分歧（高山鼠尾草）。他们发现 DE 和 DS 基因的身份和生物学功能几乎没有重叠，这表明这两种调节机制作用于不同的细胞特征以互补地改变生物体表型。此外，许多 DE 和 DS 基因可以定位到顺式-acting QTL，认为这种调节差异中的一些是基于遗传的。DE 和 DS 基因也更可能是“枢纽基因”而不是它们的非发散对应物，暗示这种调节变异可能具有多种表型效应。对三对独立进化的底栖和中上层charr 的比较发现，不同湖泊生态型之间的表达和剪接方面的平行性比预期的要大，支持这些分子表型在适应性分化中的作用。总体而言，Jacobs 和 Elmer (2021) 的发现强调了选择性剪接作为局部适应潜在机制的重要性，并为希望充分利用其 RNA-seq 数据的其他人提供了一个框架。