Dorsal spine evolution in threespine sticklebacks via a splicing change in MSX2A

Area of Science:

• Evolutionary biology
• Genetics
• Developmental biology

Background:

• Dorsal spine reduction in threespine sticklebacks is a classic example of recurrent skeletal evolution.
• Marine sticklebacks have long spines, while freshwater populations often exhibit shorter spines.
• A quantitative trait locus (QTL) on chromosome 4 influences spine length, but the causative gene remains unknown.

Purpose of the Study:

• To identify the gene and mutations responsible for repeated dorsal spine reduction in freshwater sticklebacks.
• To elucidate the molecular mechanisms underlying evolutionary changes in stickleback spine length.

Main Methods:

• Fine-scale mapping of the spine length QTL to locate the candidate gene.
• Analysis of MSX2A gene expression and splicing in marine and freshwater sticklebacks.
• Generation of transgenic freshwater sticklebacks expressing marine MSX2A to assess its functional impact on spine length.

Main Results:

• The spine length QTL was refined to the vicinity of the MSX2A transcription factor gene, which is expressed in developing spines.
• Freshwater stickleback alleles of MSX2A exhibit altered splicing, leading to increased production of a truncated, non-functional transcript.
• Transgenic fish expressing marine MSX2A showed significantly longer spines, partially reversing the freshwater phenotype.

Conclusions:

• MSX2A is a major gene driving dorsal spine reduction in freshwater sticklebacks.
• Altered splicing of MSX2A, rather than changes in protein sequence or expression levels, underlies this evolutionary adaptation.
• This study provides a compelling example of morphological evolution driven by changes in alternative splicing.