REQUISITE MUTATIONAL LOAD, PATHWAY EPISTASIS, AND DETERMINISTIC MUTATION ACCUMULATION IN SEXUAL VERSUS ASEXUAL POPULATIONS

A measure of the equilibrium load of deleterious mutations is develope d that explicitly incorporates the level of genome-wide linkage disequ ilibrium. This measure, called the requisite mutational load, is based on the minimal net reproductive rate of the least mutated class neces sary to prevent deterministic mutation accumulation. If this minimal n et reproductive rate is larger than ecological or physiological constr aints allow, then: a) the population is driven to extinction via deter ministic mutation accumulation, or b) a mutational Red-Queen ensues wi th adaptation counterbalancing mutation accumulation. Two population p arameters determine the requisite mutational load: a) the equilibrium strength of selection, measured as a selection gradient, and b) the eq uilibrium opportunity for selection, measured as the variance in numbe r of mutations per genome. The opportunity for selection is decomposed into the accumulation of mutations (average number per genome) and th e level of genome-wide linkage disequilibrium. Recombination can subst antially reduce the requisite mutational load, compared to clonal repr oduction, when there is buffering and/or reinforcing epistasis and als o when there is positive assortative mating for fitness. Recombination is advantageous because it reduces the negative (variance reducing) l inkage disequilibrium induced by beneficial epistasis. The functional form of the expression for requisite mutational load illustrates why e pistasis within pathways, i.e., among closely interacting genes, is a powerful alternative to genome-wide truncation selection, as a means o f reducing mutational load.