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, <i>Myosin Heavy Chain 3 Cluster C</i> (<i>MYH3C</i>), compared to marine populations. Differences in copy number between marine and freshwater fish are maintained even in the presence of gene flow, suggesting that <i>MYH3C</i> changes represent adaptive divergence between ecotypes. Copy number expansion occurs by tandem duplication of <i>MYH3C</i> coding and regulatory regions on the stickleback sex chromosome. We identify a muscle regulatory enhancer within the expanded <i>MYH3C</i> region and show that elevated copy number is associated with developmental and tissue-specific increases in corresponding mRNA expression levels in skeletal muscle. Common <i>MYH3C</i> 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.
Authors
- John A. Baker (ORCID: https://orcid.org/0000-0002-3713-8068)
- Yingguang Frank Chan (ORCID: https://orcid.org/0000-0001-6292-9681)
- Felicity C. Jones (ORCID: https://orcid.org/0000-0002-5027-1031)
- Kathleen T. Xie (ORCID: https://orcid.org/0000-0002-3178-8959)
- Shannon D. Brady (ORCID: https://orcid.org/0000-0002-5714-6129)
- Emily E. Hare
- Jane Grimwood (ORCID: https://orcid.org/0000-0002-8356-8325)
- Jeremy Schmutz (ORCID: https://orcid.org/0000-0001-8062-9172)
- Alex A. Pollen (ORCID: https://orcid.org/0000-0003-3263-8634)
- T. E. Reimchen (ORCID: https://orcid.org/0000-0002-5578-8531)
- Garrett A. Roberts Kingman (ORCID: https://orcid.org/0000-0002-1910-3005)
- Emma Offenberg
- Bjarni Jónsson
- Heidi I. Chen (ORCID: https://orcid.org/0000-0003-1744-8461)
- Eric H. Au (ORCID: https://orcid.org/0000-0001-5889-296X)
- Miguel L. Reyes (ORCID: https://orcid.org/0000-0002-1311-6868)
- David C. Heins (ORCID: https://orcid.org/0000-0002-6175-8777)
- Craig B. Lowe (ORCID: https://orcid.org/0000-0002-6838-1976)
- Rhea R. Daugherty
- Dolph Schluter
- Alyssa M Yoxsimer
- Haili Zhang
- Michael A Bell
- Timothy R Howes
- David M Kingsley
- Richard M Myers
Institutions
- Tulane University (US)
- Clark University (US)
- Museum of Vertebrate Zoology (US)
- Howard Hughes Medical Institute (US)
- University of British Columbia (CA)
- Emory University (US)
- University of Groningen (NL)
- Duke University (US)
- University of California, San Francisco (US)
- Pfizer (United States) (US)
- Hólar University College (IS)
- University of Victoria (CA)
- Duke Medical Center (US)
- HudsonAlpha Institute for Biotechnology (US)
- Broad Center (US)
- Duke University Hospital (US)
- Reykjavík Energy (Iceland) (IS)
- Stanford University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2025-12-25
- DOI
- https://doi.org/10.64898/2025.12.22.696110
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- University of Washington
- Tulane University
- National Institutes of Health
- Center for Computational, Evolutionary and Human Genomics, Stanford University