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New Research on Epistatic Interactions Shows "Overwhelmingly Negative" Fitness Costs and Limits to Evolution

Two new papers published in the journal Science are reporting the results of studies on genetic interactions of mutations--a phenomenon called epistasis. While epistasis is sometimes cited as a potential mechanism for improving evolutionary fitness or overcoming fitness costs, these studies found the opposite. According to the research, as mutations--even beneficial mutations--accumulated, negative interactions among the mutations caused fitness increase at a much slower rate, resulting in "diminishing returns". A ScienceDaily news release discussed the papers, stating:

"The motivation for this experiment comes from wanting to understand the factors involved in the evolution of organisms to better 'fit' their environment," Cooper said. "The lack of information on how mutations interact with one another has been a major gap in predicting how populations evolve. Our work shows how we can perform experiments to fill this gap, giving us a better understanding."

Cooper and his team focused on a bacterial population that had been evolved for thousands of generations such that its fitness had increased by approximately 35 percent over its ancestor. In identifying the beneficial mutations that arose in the population and adding all possible combinations of these mutations to the ancestor strain, however, they found that combinations of mutations acted in a surprising, yet simple, way. The more mutations the researchers added, the more they interfered with each other. It was as if the mutations got in each other's way as they all tried to accomplish the same thing.

It was found that the beneficial mutations allowing the bacteria to increase in fitness didn't have a constant effect. The effect of their interactions depended on the presence of other mutations, which turned out to be overwhelmingly negative.

"These results point us toward expecting to see the rate of a population's fitness declining over time even with the continual addition of new beneficial mutations," he said. "As we sometimes see in sports, a group of individual stars doesn't necessarily make a great team."


A similar study from the lab of Chris Marx at Harvard University is being published in Science simultaneously with Cooper's paper. Marx studied interactions between beneficial mutations arising in a different bacterium evolving in a different medium, yet also found a general trend toward diminishing returns. (emphasis added)

The research paper published out of the Cooper lab (with Richard Lenski as a co-author), by Khan et al., is titled "Negative Epistasis Between Beneficial Mutations in an Evolving Bacterial Population." It found that "Epistasis depended on the effects of the combined mutations--the larger the expected benefit, the more negative the epistatic effect. Epistasis thus tended to produce diminishing returns with genotype fitness, although interactions involving one particular mutation had the opposite effect. These data support models in which negative epistasis contributes to declining rates of adaptation over time."

The other paper from the Marx lab, by Chou et al., is titled "Diminishing Returns Epistasis Among Beneficial Mutations Decelerates Adaptation." The article's abstract likewise explains that: "patterns of epistasis may differ for within- and between-gene interactions during adaptation and that diminishing returns epistasis contributes to the consistent observation of decelerating fitness gains during adaptation."

The title of a summary piece in Science tells the whole story: "In Evolution, the Sum Is Less than Its Parts." It notes that these studies encountered "antagonistic epistasis," where negative effects arise from epistatic interactions:

Both studies found a predominance of antagonistic epistasis, which impeded the rate of ongoing adaptation relative to a null model of independent mutational effects.
In essence, these studies found that there is a fitness cost to becoming more fit. As mutations increase, bacteria faced barriers to the amount they could continue to evolve. If this kind of evidence doesn't run counter to claims that neo-Darwinian evolution can evolve fundamentally new types of organisms and produce the astonishing diversity we observe in life, what does?