Fig. 5

Evolution starting from the ‘centre’ of the landscape (double mutants) cannot cross the single mutant valley en route to the wild type ancestor (0000). These are illustrative examples of individual simulations of evolution without drug when the starting population is composed equally of the double mutants: 1100, 1010, 1001, 0011, 0101, and 0110. Broadly speaking, one can observe three different outcomes after 1000 generations: a fixation of the third-site (**1*) in the double mutant (0110), b a third-site-carrying triple mutant (1110) or c a “polymorphic” population with 0110, 1101 and 1110 all present in frequency space after 1000 generations (but headed towards an eventual fixation of 1110). No simulations starting from the centre moved in the reverse direction toward the ancestral allele (0000)