Molecular mechanisms of Eda-mediated adaptation to freshwater in threespine stickleback

Carlos E. Rodríguez-Ramírez, Melanie Hiltbrunner, Verena Saladin, Stephanie Walker, Araxi Urrutia, Catherine L. Peichel

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalMolecular Ecology
Early online date16 May 2023
Publication statusE-pub ahead of print - 16 May 2023

Bibliographical note

Funding Information:
We are grateful to Pooja Singh and Magdalena Bohutínská for very helpful discussions and feedback on the manuscript, Sophie Archambeault for setting up the lineages used in this study, all Peichel Lab members for fruitful discussions throughout the study, and the University of Bern Next Generation Sequencing Center for library preparation and sequencing. This work was funded by the University of Bern. Open access funding provided by Universitat Bern. Eda

Benefits from this research accrue from the sharing of our data and results on public databases as described above.


  • alternative splicing
  • Eda
  • genetics of adaptation
  • lateral line
  • lateral plates
  • threespine stickleback

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics


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