Molecular mechanisms ofEda‐mediated adaptation to freshwater in threespine stickleback

Abstract

A main goal of evolutionary biology is to understand the genetic basis of adaptive evolution. Although the genes that underlie some adaptive phenotypes are now known, the molecular pathways and regulatory mechanisms mediating the phenotypic effects of those genes often remain a black box. Unveiling this black box is necessary to fully understand the genetic basis of adaptive phenotypes, and to understand why particular genes might be used during phenotypic evolution. Here, we investigated which genes and regulatory mechanisms are mediating the phenotypic effects of the Eda haplotype, a locus responsible for the loss of lateral plates and changes in the sensory lateral line of freshwater threespine stickleback (Gasterosteus aculeatus) populations. Using a combination of RNAseq and a cross design that isolated the Eda haplotype on a fixed genomic background, we found that the Eda haplotype affects both gene expression and alternative splicing of genes related to bone development, neuronal development and immunity. These include genes in conserved pathways, like the BMP, netrin and bradykinin signalling pathways, known to play a role in these biological processes. Furthermore, we found that differentially expressed and differentially spliced genes had different levels of connectivity and expression, suggesting that these factors might influence which regulatory mechanisms are used during phenotypic evolution. Taken together, these results provide a better understanding of the mechanisms mediating the effects of an important adaptive locus in stickleback and suggest that alternative splicing could be an important regulatory mechanism mediating adaptive phenotypes.

The role of alternative splicing in marine-freshwater divergence in threespine stickleback

“…We found 1852 DEGs, 109 DSGs and 30 DESGs (Figure 2a). This disparity in abundance of DEGs and DSGs is a pattern commonly found in other studies (Grantham and Brisson 2018;Jacobs and Elmer 2021;Steward et al 2022;Rodríguez-Ramírez et al 2023), though not always (Singh et al 2017).…”

“…Methods based on differential exon usage have been used in other studies (e.g. Singh et al, 2017; Jacobs & Elmer 2021; Rodríguez-Ramírez et al, 2023) and can use most of the same reads as DE analyses but cannot detect certain types of splicing (i.e. A3SS and A5SS).…”

Heterogeneous genomic architecture of skeletal armour traits in sticklebacks

“…Furthermore, we identified Bmp2k on LG13 as a candidate gene that impacts plate number variation in the nine-spined stickleback, and Bmp7 on LG17 as a gene that potentially influences both plate number and plate width (although not plate area or height). Similarly, a recent study in the three-spined stickleback also found that the BMP pathway is a strong candidate mediating the effect of Eda on the development of lateral plates (Rodríguez-Ramírez et al 2023). However, as all of the QTL regions in our study included tens to hundreds of genes, little confidence can be assigned to the identified candidate genes.…”

Developmental tinkering of gene regulation facilitated super rapid adaptive radiation

“…In the butterfly Bicyclus anynana more than half of the genes that were differentially expressed were also differentially spliced but none of the genes associated with seasonal plasticity were differentially expressed and alternatively spliced ( Steward et al 2022 ). Similarly a recent study on the Eda haplotype in sticklebacks found only a small overlap (six genes) of gene expression and alternative splicing, but a lot of differentially spliced genes (no significant enrichment) were involved in the same biological processes as the differentially expressed ones ( Rodríguez-Ramírez et al 2023 ).…”