Pervasive Cryptic Epistasis in Molecular Evolution
Figure 2
The evolution of cryptic epistasis.
(A) Two lineages diverge from the most recent common ancestor (MRCA), genotype ab. Each fixes a mutation to produce genotypes Ab and aB. The presence of either mutation prevents the second becoming fixed because the double mutant, genotype AB, is deleterious. Cryptic epistasis is revealed upon moving mutation A from species 1 into species 2 or moving mutation B from species 2 into species 1 (gray arrows). Moving mutations a or b to form genotype ab restores the ancestral functional state. (B) Cryptic epistasis can also occur when both mutations arise in the same lineage leading to species 1. In this case cryptic epistasis is revealed upon moving mutation a into species 1 or mutation B into species 2 (gray arrows). Moving mutations A or b to form genotype Ab regenerates a functional evolutionary intermediate.