Rapid and repeated evolution of myosin copy number in threespine stickleback
Copy number variants at genomic loci evolve at a high rate, are linked to many different diseases, and play a role in adaptive evolution in humans and other organisms. Here we show that stickleback fish from freshwater environments have rapidly and repeatedly evolved an expanded number of copies of a gene family involved in muscle development, Myosin Heavy Chain 3 Cluster C (MYH3C), compared to marine populations. Differences in copy number between marine and freshwater fish are maintained even in the presence of gene flow, suggesting that MYH3C changes represent adaptive divergence between ecotypes. Copy number expansion occurs by tandem duplication of MYH3C coding and regulatory regions on the stickleback sex chromosome. We identify a muscle regulatory enhancer within the expanded MYH3C region and show that elevated copy number is associated with developmental and tissue-specific increases in corresponding mRNA expression levels in skeletal muscle. Common MYH3C clusters include 3-, 4-, 5-, and 6-copy variants that likely evolved through a combination of microhomology-mediated break repair and non-allelic homologous recombination. Our results provide a new example of copy number changes in a wild species and identify CNVs as potential "hotspots" of repeated adaptive evolution.