Repeated evolutionary turnover of vertebrate skeletal muscle myosins

Christina M. Harvey, Eric R. Schuppe, Michael S. Brainard, Matthew J. Fuxjager, James B. Pease. Proc. R. Soc. B (2026) 293 (2070): 20260254. DOI: 10.1098/rspb.2026.0254

Abstract

Myosin heavy chain proteins are essential for muscle contraction and nearly every physiological function in animals, but their diversity and evolution outside mammals are largely unknown. We comprehensively model the evolutionary history of 1201 heavy-chain myosins from across Chordata. We find that skeletal muscle myosins are located in a conserved tandem gene array in all vertebrate species, but repeated gene duplication-loss turnover has surprisingly led to an independently evolved set of core skeletal muscle myosins in each major vertebrate group. Despite these separate derivations of these myosin subfamilies, each major vertebrate group exhibits tissue-specific patterns of subfamily expression and specialized myosin subfamily expression in extreme muscles. Our results show that muscle evolution across vertebrates is not based on conserved one-to-one orthologous motor myosins, as might be expected for such a core structural protein family. Instead, we find that skeletal muscle myosins have evolved as a shifting cluster of genes that is constantly changing and diversifying to balance maintenance of core physiological processes and innovation of new physiological possibilities.