directional epistasis
Chou H-H, Chiu H-C, Delaney NF, Segré D & Marx CJ 2011 Diminishing returns epistasis among beneficial mutations decelerates adaptation. Science 332:1190-1192.
- epistasis has substantial impacts on evolution, in particular, the rate of adaptation
- the proportional selective benefit for three of the four loci consistently decreased when they were introduced onto more fit backgrounds
- patterns of epistasis may differ for within- and between-gene interactions during adaptation
- diminishing returns epistasis contributes to the consistent observation of decelerating fitness gains during adaptation
- epistasis describes genetic interactions in terms of how phenotypic effects of a mutation depend on other mutations in the genome
- the detrimental effect of a lesion in a pathway (or module) (4) is greater alone than when there is already another deleterious mutation in that process (i.e., antagonistic epistasis)
- lesions in parallel pathways producing the same product tend to cause stronger phenotypes (synergistic epistasis) than expected
- epistasis between beneficial mutations remains largely unexplored
- few studies have addressed interactions between beneficial mutations in different genes
- the most consistent finding across studies of laboratory-evolved populations has been a rapid deceleration of the rate of fitness increase
- theoretical analysis suggests that the observed dynamics of fitness increase and accumulation of substitutions (11) are best described by a class of fitness landscapes with antagonistic interactions between beneficial mutations
- the nonlinearity of fitness increase in these models arises because it is assumed that a given trait is under stabilizing selection for an intermediate optimum, which explicitly considers fitness as being displaced from a fixed adaptive peak
- we considered a higher-level phenotype (growth rate) as the sum of two constituent phenotypes (metabolic rate and protein expression burden), which allowed us to generate a precise expectation for the fitness of multiallele strains without explicitly assuming stabilizing selection
- across these two distinct model systems 7 of 10 alleles consistently showed antagonism
- only 2 exhibited synergy
- this tendency toward diminishing returns between beneficial mutations was predicted from trajectories of fitness increase and substitution rate (12) but had never been tested directly
- these results are in stark contrast to the epistatic effects seen among mutations within single proteins, which are varying and unpredictable in their effect with regard to background activity
- this distinction between results from within- and between-gene epistasis suggests that the underlying causes of epistasis at different physiological scales (i.e., within-gene protein biophysics versus between-gene physiological networks) lead to categorically distinct, but reproducible, trends in genetic interactions that affect both the speed of adaptation and the degree to which possible trajectories are limited
