LINKAGE AND THE LIMITS TO NATURAL-SELECTION

The probability of fixation of a favorable mutation is reduced if sele ction at other loci causes inherited variation in fitness. A general m ethod for calculating the fixation probability of an allele that can f ind itself in a variety of genetic backgrounds is applied to find the effect of substitutions, fluctuating polymorphisms, and deleterious mu tations in a large population. With loose linkage, r, the effects depe nd on the additive genetic variance in relative fitness, var(W), and a ct by reducing effective population size by (N / N-e) = 1 + var(W) / 2 r(2). However, tightly linked loci can have a substantial effect not p redictable from N-e. Linked deleterious mutations reduce the fixation probability of weakly favored alleles by exp(-2U / R), where U is the total mutation rate and R is the map length in Morgans. Substitutions can cause a greater reduction: an allele with advantage s < s(crit) = (pi(2) / 6) log(e)(S / s) [var(W) / R] is very unlikely to be fixed. ( S is the advantage of the substitution impeding fixation.) Fluctuating polymorphisms at many (n) linked loci can also have a substantial eff ect, reducing fixation probability by exp[root 2Kn var (W) / R] [K = - 1 / E((u - (u) over bar)(2) / uv) depending (u,v) at the selected poly morphisms]. Hitchhiking due to all three kinds of selection may substa ntially impede adaptation that depends on weakly favored alleles.