Abstract
BackgroundThe rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. However, in a number of recent studies, a prevalence of antagonistic epistasis (the tendency of multiple mutations to have a mitigating rather than reinforcing effect) has been observed.ResultsWe studied in silico the net amount and form of epistatic interactions in RNA secondary structure folding by measuring the fraction of neutral mutants as a function of mutational distance d. We found a clear prevalence of antagonistic epistasis in RNA secondary structure folding. By relating the fraction of neutral mutants at distance d to the average neutrality at distance d, we showed that this prevalence derives from the existence of many compensatory mutations at larger mutational distances.ConclusionsOur findings imply that the average direction of epistasis in simple fitness landscapes is directly related to the density with which fitness peaks are distributed in these landscapes.
Highlights
The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories
Synergistic epistasis means that the decline in average fitness accelerates as more random mutations are added
Lines represent best fits [function exp(- α dβ) for w(d), and function md + n for average neutrality]. (a): A case of strongly antagonistic epistasis (β = 0.688), which is associated with increasing neutrality with d. (b): A more synergistic case (β = 1.017), and a corresponding decline in neutrality with d
Summary
The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. It might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. If mutations are randomly added to an organism's genome (as opposed to incorporated by natural selection), fitness tends to decline with mutation number. Synergistic epistasis means that the decline in average fitness accelerates as more random mutations are added (such epistasis is termed negative by Phillips et al [1]). If deleterious mutations interact so that their combined effect is smaller than expected under the multiplicative model, epistasis is called antagonistic (or positive in the terminology of Phillips et al.). Antagonistic epistasis implies unexpected robustness to the effects of multiple deleterious mutations [2]
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