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Pervasive natural selection can strongly influence observed patterns ofgenetic variation, but these effects remain poorly understood when multipleselected variants segregate in nearby regions of the genome. Classicalpopulation genetics fails to account for interference between linked mutations,which grows increasingly severe as the density of selected polymorphismsincreases. Here, we describe a simple limit that emerges when interference iscommon, in which the fitness effects of individual mutations play a relativelyminor role. Instead, molecular evolution is determined by the variance infitness within the population, defined over an effectively asexual segment ofthe genome (a ``linkage block''). We exploit this insensitivity in a new``coarse-grained'' coalescent framework, which approximates the effects of manyweakly selected mutations with a smaller number of strongly selected mutationswith the same variance in fitness. This approximation generates accurate andefficient predictions for the genetic diversity that cannot be summarized by asimple reduction in effective population size. However, these results suggest afundamental limit on our ability to resolve individual selection pressures fromcontemporary sequence data alone, since a wide range of parameters yield nearlyidentical patterns of sequence variability.

Interference limits resolution of selection pressures from linked neutral diversity