For many years, scientists studying evolution have believed that most genetic changes influencing how genes and proteins evolve are essentially neutral. These mutations were thought to be neither harmful nor helpful, allowing them to pass through natural selection without much notice.

A new study from the University of Michigan challenges this long-held view.

As species evolve, mutations arise and sometimes become fixed, meaning every member of a population eventually carries the same change. The Neutral Theory of Molecular Evolution argues that most fixed mutations fall into this neutral category. Harmful mutations are expected to be removed by natural selection, and beneficial ones are considered so uncommon that neutral changes should dominate, explains evolutionary biologist Jianzhi Zhang.

Zhang and his team set out to test this assumption. Their analysis revealed that beneficial mutations appear far more often than the Neutral Theory allows. At the same time, the actual rate at which mutations become fixed is much too low to match the high number of advantageous changes the researchers documented.

Environmental Shifts and the Fate of Mutations
To explain the mismatch in their results, the researchers propose that a mutation that helps an organism in one setting can become harmful when conditions shift. Because environments often change, these useful mutations may disappear before they have time to become fixed in a population. The work, funded by the U.S. National Institutes of Health, appears in the journal Nature Ecology and Evolution.

“We’re saying that the outcome was neutral, but the process was not neutral,” said Zhang, U-M professor of ecology and evolutionary biology. “Our model suggests that natural populations are not truly adapted to their environments because environments change very quickly, and populations are always chasing the environment.”

Zhang says their new theory, called Adaptive Tracking with Antagonistic Pleiotropy, tells us something about how well all living things are adapted to their environments.

“I think this has broad implications. For example, humans. Our environment has changed so much, and our genes may not be the best for today’s environment because we went through a lot of other different environments. Some mutations may be beneficial in our old environments, but are mismatched to today,” Zhang said. 

“At any time when you observe a natural population, depending on when the last time the environment had a big change, the population may be very poorly adapted or it may be relatively well adapted. But we’re probably never going to see any population that is fully adapted to its environment, because a full adaptation would take longer than almost any natural environment can remain constant.”