Alternative splicing: An overlooked mechanism contributing to local adaptation?

Abstract

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.

Acute thermal stress elicits interactions between gene expression and alternative splicing in a fish of conservation concern

“…Given the broad importance of intron splicing in fishes and other organisms (Chaudhary et al, 2019; De Nadal et al, 2011; Healy and Schulte, 2019; Kornblihtt et al, 2013; Laloum et al, 2018; Li et al, 2020; Salisbury et al, 2021; Tan et al, 2019; Thorstensen et al, 2021; Xia et al, 2018; Zhang et al, 2019), we hypothesised that alternative splicing is an important component of the transcriptome response to thermal stress in redside dace. Therefore, we analyzed alternative splicing (measured by differential exon usage) for its possible roles in the acute stress response and interactions with gene expression.…”

“…While mRNA abundance most accurately reflects gene transcription (Buccitelli and Selbach, 2020; Jeffries et al, 2021), tests of differential abundance of mRNA transcripts are commonly referred to as tests of differential gene expression in transcriptomics studies (e.g., Conesa et al, 2016). In addition to tests of mRNA abundance, RNA-sequencing also enables tests of alternative splicing (Salisbury et al, 2021). Instead of mRNA abundance changing in response to a stressor as in transcriptomics, exons within genes are differentially assembled in post-transcriptional modifications of RNA.…”

“…While mRNA abundance is better understood than alternative splicing in the eukaryotic stress response (Salisbury et al, 2021), splicing also contributes to controlling stress responses in plants, yeast, fruit flies, shrimp, and humans (Chaudhary et al, 2019; De Nadal et al, 2011; Kornblihtt et al, 2013; Laloum et al, 2018; Zhang et al, 2019). Furthermore, recent studies indicate that alternative splicing is a key element of the response to environmental change in fishes, such as salinity changes (Thorstensen et al, 2021), acute hypoxia (Xia et al, 2018), cold acclimation (Healy and Schulte, 2019), cold stress (Li et al, 2020), and heat stress (Tan et al, 2019).…”

“…Furthermore, recent studies indicate that alternative splicing is a key element of the response to environmental change in fishes, such as salinity changes (Thorstensen et al, 2021), acute hypoxia (Xia et al, 2018), cold acclimation (Healy and Schulte, 2019), cold stress (Li et al, 2020), and heat stress (Tan et al, 2019). Differential splicing also contributes to evolutionary change including local adaptation of ecotypes (Jacobs and Elmer, 2021; Salisbury et al, 2021) and speciation (Singh et al, 2017; Terai et al, 2003). However, relatively little is known about changes in splicing following an acute thermal stress event (Tan et al, 2019).…”

Multidimensional plasticity jointly contributes to rapid acclimation to environmental challenges during biological invasions

“…Gene expression change, however, is not the only intermediate regulatory process linking genotypes and phenotypic traits. Alternative splicing (AS), as an important co- or post-transcriptional mechanism of generating multiple mRNA isoforms from a single gene, has received relatively less attention despite its importance in adaptation (Salisbury et al 2021; Verta and Jacobs 2022). Several recent studies have demonstrated the contribution of AS to phenotypic novelty such as the caste differentiation of bumble bee (Price et al 2018) and parallel ecological adaptation of ecotype-specific feeding morphology in a salmonid fish (Jacobs and Elmer 2021).…”