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

Abstract

BackgroundDorsal spine reduction in threespine sticklebacks (Gasterosteus aculeatus) is a classic example of recurrent skeletal evolution in nature. Sticklebacks in marine environments typically have long spines that form part of their skeletal armor. Many derived freshwater populations have evolved shorter spines. Changes in spine length are controlled in part by a quantitative trait locus (QTL) previously mapped to chromosome 4, but the causative gene and mutations underlying the repeated evolution of this interesting skeletal trait have not been identified.ResultsRefined mapping of the spine length QTL shows that it lies near the MSX2A transcription factor gene. MSX2A is expressed in developing spines. In F1 marine × freshwater fish, the marine allele is preferentially expressed.Differences in expression can be attributed to splicing regulation. Due to the use of an alternative 5 ′ splice site within the first exon, the freshwater allele produces greater amounts of a shortened, non-functional transcript and makes less of the full-length transcript. Sequence changes in the MSX2A region are shared by many freshwater fish, suggesting that repeated evolution occurs by reuse of a spine-reduction variant.To demonstrate the effect of full-length MSX2A on spine length, we produced transgenic freshwater fish expressing a copy of marine MSX2A. The spines of the transgenic fish were significantly longer on average than those of their non-transgenic siblings, partially reversing the reduced spine lengths that have evolved in freshwater populations.Conclusions MSX2A is a major gene underlying dorsal spine reduction in freshwater sticklebacks. The gene is linked to a separate gene controlling bony plate loss, helping explain the concerted effects of chromosome 4 on multiple armor-reduction traits. The nature of the molecular changes provides an interesting example of morphological evolution occurring not through a simple amino acid change, nor through a change only in gene expression levels, but through a change in the ratio of splice products encoding both normal and truncated proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-017-0456-5) contains supplementary material, which is available to authorized users.

Genetics of adaptation: Experimental test of a biotic mechanism driving divergence in traits and genes

“…indicated that length of the first dorsal spine maps to the region containing Msx2a on chromosome IV, and length of the pelvic spine and pelvic girdle map to the Pitx1 region on chromosome VII, consistent with previous work (Chan et al. ; Howes et al ). In the QTL maps within each F 1 family peaks on chromosome IV near Msx2a explained an average of 9% of the variance (PVE) in first dorsal spine length and the peaks on chromosome VII near Pitx1 explained on average 57% of the variance in pelvic spine length, depending on family (see Table for individual F 1 family values).…”

“…; Howes et al. ). Future experiments are needed to disentangle individual genetic contributions to divergent evolution.…”

“…; Howes et al. ), which identified genes contributing to variation in bony armor. Using artificial ponds, we manipulated a potential agent of selection on traits and key genes at a realistic biological scale.…”

“…This is because Msx2a is located in a region of low recombination (Howes et al. ) also known to contain other genes affecting armor, body shape, and trophic traits (Albert et al. ; Howes et al.…”

“…), and reduced dorsal spine length results from a splicing variant of the Msx2a gene (Howes et al. ). We test the hypothesis that interactions between the two coevolving stickleback species and a vertebrate predator have led to divergence in these armor traits and genes.…”