COLUMBUS, Ohio – Within every muscle of every living species with a backbone, a protein called myosin tugs on a partner protein to generate a muscle contraction. This function, discovered in mammals a century ago, has been presumed by scientists to be operating in the same way among birds, reptiles, amphibians and fish.
A new study tells a different story. These two proteins, myosin and actin, always work together to activate a muscle, but tiny variations in how they interact change the speed, frequency and energy consumption associated with myosin’s movement – and, as a result, define the nature of a given animal’s related muscle function. An analysis of historic genomic data across species revealed about 50 previously unidentified gene subfamilies that drive those subtle but meaningful differences.
The findings suggest that the evolution of animals as disparate as salmon, snakes, eagles and elephants isn’t explained only by their external appearance. Instead, diversity and adaptation may be prompted at least in part by factors nestled deep under the surface as a response to species-specific muscular needs.
“A lot of the story of vertebrate evolution has to do with these incredibly different body forms and different physiologies, while the core machinery has been treated as a constant,” said James Pease , senior author of the study and associate professor of evolution, ecology and organismal biology at The Ohio State University .
“What we found is that the core machinery is actually quite variable. Musculoskeletal innovations may be a rather large and underappreciated component of the story of vertebrate evolution.”
The work was led by first author Christina Harvey , a 2026 biology PhD graduate of Wake Forest University, where Pease was a faculty member until 2024. Harvey is now an assistant professor at High Point University.
The research was published recently in Proceedings of the Royal Society B .
Pease and colleagues pursued the myosin mystery after studying a different musculoskeletal protein in birds that perform dramatic overhead wing snaps. First comparing the mammalian myosin gene profile to the chicken genome, they saw a huge difference in the number of genes in the respective region of each genome relevant to muscle movement. Further investigation showed this was not an isolated phenomenon.
“Everything we’ve assumed for how a mammal’s muscles work, we’ve applied outside of mammals to these other groups. But when we pulled in more and more genes over time, we found that the story was more complex than that,” Harvey said.
Accessing hundreds of samples from publicly available genomic data, the team modeled 500 million years of evolutionary history of the genes for 1,201 myosins, showing that each vertebrate group is equipped with its own set of core skeletal muscle myosin proteins.
“With the advent of molecular biology and being able to explore things at the protein and gene level, we’ve untangled that while the traits that we see on the surface seem very similar, the routes that they’ve taken to get there through molecular processes have been very distinct and very different,” Harvey said. “Every major group of vertebrates exhibits its own distinct gene turnover.”
Even within a species, these proteins can be highly specialized: In the rattlesnake, different myosin molecules govern muscle activity in the head and middle segments, and muscles surrounding the rattle on the tail have a high concentration of one type of myosin that had never been documented before, Pease said.
Overall, the researchers proposed new names for at least 50 previously unknown subfamilies of myosin genes, adding to the 15 existing sub-types.
“There are many, many more genes that have yet to be identified individually. I like to think that these 50 new subfamilies represent diversity across vertebrates that was previously unrecognized,” Harvey said.
Myosin expression patterns have traditionally been studied in mammals in the context of whether muscles belong in the slow-twitch or fast-twitch category, with slow-twitch enabling, for example, humans to hold up their necks all day.
“The new subtypes are a window into a new paradigm: The molecular basis of what makes a fast-twitch or slow-twitch muscle in mammals doesn’t translate to birds or to lizards or to fish. It’s a different molecular basis,” Pease said.
The findings can’t explain what drove these molecular changes, and diversification is usually explained by an organism’s need to respond to changes in the external environment – like an emerging pathogen. The bar for proving adaptation has occurred is high, so the team can only make inferences based on the evidence at hand.
“What we would say in a conservative way is that if this diversity of all of these molecular subtypes weren’t important, there would probably be only one type of myosin,” Pease said. “These different molecules that are new had specific roles, and this process is overturning and changing, but these molecules are not identical copies. They’re diversifying. And that’s really unlikely to happen over and over and over again if these aren’t being driven by some kind of selective or adaptive process.”
This work was supported by the U.S. National Science Foundation and the Howard Hughes Medical Institute.
Additional co-authors were Eric Schuppe and Michael Brainard of the University of California, San Francisco, and Matthew Fuxjager of Brown University.
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Contacts:
James Pease, Pease.25@osu.edu
Christina Harvey, charvey3@highpoint.edu
Written by Emily Caldwell, Caldwell.151@osu.edu ; 614-292-8152
Repeated evolutionary turnover of vertebrate skeletal muscle myosins