Evolutionary theorist Stephen Jay Gould is famous for describing the evolution of humans and other conscious beings as a chance accident of history. If we could go back millions of years and "run the tape of life again," he mused, evolution would follow a different path.
A study by University of Pennsylvania biologists now provides evidence Gould was correct, at the molecular level: Evolution is both unpredictable and irreversible. Using simulations of an evolving protein, they show that the genetic mutations that are accepted by evolution are typically dependent on mutations that came before, and the mutations that are accepted become increasingly difficult to reverse as time goes on.
The study focuses exclusively on the type of evolution known as purifying selection, which favors mutations that have no or only a small effect in a fixed environment. This is in contrast to adaptation, in which mutations are selected if they increase an organism’s fitness in a new environment. Purifying selection is by far the more common type of selection.
"It’s the simplest, most boring type of evolution you can imagine," Plotkin said. "Purifying selection is just asking an organism to do what it’s doing and keep doing it well."
As an evolutionary model, the Penn team used the bacterial protein argT, for which the three-dimensional structure is known. Its small size means that the researchers could reliably predict how a given genetic mutation would affect the protein’s stability.
Using a computational model, they simulated the protein evolving during the equivalent of roughly 10 million years by randomly introducing mutations, accepting them if they did not significantly affect the protein’s stability and rejecting them if they did. They then examined pairs of mutations, asking whether the later mutation would have been accepted had the earlier mutation not have been made.
"The very same mutations that were accepted by evolution when they were proposed, had they been proposed at a much earlier in time, they would have been deleterious and would have been rejected," Plotkin said. This result, that later mutations were dependent on the earlier ones, demonstrates a feature known as contingency. In other words, mutations that are accepted by evolution are contingent upon previous mutations to ameliorate their effects.