Abstract
To escape from local fitness peaks, a population must navigate across valleys of low fitness. How these transitions occur, and what role they play in adaptation, have been subjects of active interest in evolutionary genetics for almost a century. However, to our knowledge, this problem has never been addressed directly by considering the evolution of a gene, or group of genes, as a whole, including the complex effects of fitness interactions among multiple loci. Here, we use a precise model of protein fitness to compute the probability that an allele, randomly sampled from a population at time t, has crossed a fitness valley of depth s during an interval in the immediate past. We study populations of model genes evolving under equilibrium conditions consistent with those in mammalian mitochondria. From this data, we estimate that genes encoding small protein motifs navigate fitness valleys of depth with probability on a time scale of human evolution, where N is the (mitochondrial) effective population size. The results are consistent with recent findings for Watson–Crick switching in mammalian mitochondrial tRNA molecules.
Highlights
The effect of a mutation on the fitness of an organism usually depends on the genetic background, or context in which it occurs, a phenomenon known as epistasis [1,2]
If we assume that the fitness landscapes of proteins with 16 amino acids can be used to represent the landscapes of larger chains, e.g., doubling the mutation rate per gene will have the same effect as doubling the chain length to obtain a protein encoded by the same amount of genetic material as a tRNA molecule or small protein motif [42]
Does the model provide an accurate picture of fitness valley crossing for small protein motifs?
Summary
The effect of a mutation on the fitness of an organism usually depends on the genetic background, or context in which it occurs, a phenomenon known as epistasis [1,2]. We find that, even on the time scale of human evolution, genes encoding small protein motifs evolving under conditions consistent with mammalian mitochondria already navigate fitness valleys of depth 2Ns & 30 with probability P & 0.1, in rough agreement with the estimate for Watson–Crick switching in mt tRNAs provided by Meer et al.
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