INTERACTION OF SELECTION AND RECOMBINATION IN THE FIXATION OF NEGATIVE-EPISTATIC GENES

We investigated the interaction of recombination and selection on the process of fixation of two linked loci with epistatic interactions in fitness. We consider both the probability of fixation of newly arising mutants (the static model) and the time to fixation under continued m utation (the dynamic model). Our results show that the fixation of a n ew advantageous combination is facilitated by higher fitness of the ad vantageous genotype and by weaker selection against the intermediate d eleterious genotypes. Fixation occurs more rapidly when the recombinat ion rates are small, except when selection against intermediate genoty pes is weak and selection in favour of the double mutant is very stron g. In these cases fixation is more rapid when the recombinant rate is large. Mutations of strong effects, deleterious when alone but benefic ial when coupled, are fixed more easily than mutations of intermediate effects, at least for large recombination rates. Among the possible p athways the process of fixation might follow, independent substitution s lead to the fixation of the double mutant only when selection is wea k. The relative importance of the other pathways depends on the intera ction between recombination and selection. The coupled-gamete pathway (i.e. when the population waits until the double mutant appears and th en drives it to fixation) is more important as selection intensity inc reases and the recombination rate is reduced. For all recombination ra tes, asymmetries in fitness of the intermediate genotypes increase the rate at which fixations occur. Finally, throughout the fixation proce ss, the population will be monomorphic at least at one of the two loci for most of the time, which implies that there would be little opport unity to detect the presence of negative epistasis even if it were imp ortant for occasional evolutionary transitions.