  Pervasive natural selection can strongly influence observed patterns of
genetic variation, but these effects remain poorly understood when multiple
selected variants segregate in nearby regions of the genome. Classical
population genetics fails to account for interference between linked mutations,
which grows increasingly severe as the density of selected polymorphisms
increases. Here, we describe a simple limit that emerges when interference is
common, in which the fitness effects of individual mutations play a relatively
minor role. Instead, molecular evolution is determined by the variance in
fitness within the population, defined over an effectively asexual segment of
the genome (a ``linkage block''). We exploit this insensitivity in a new
``coarse-grained'' coalescent framework, which approximates the effects of many
weakly selected mutations with a smaller number of strongly selected mutations
with the same variance in fitness. This approximation generates accurate and
efficient predictions for the genetic diversity that cannot be summarized by a
simple reduction in effective population size. However, these results suggest a
fundamental limit on our ability to resolve individual selection pressures from
contemporary sequence data alone, since a wide range of parameters yield nearly
identical patterns of sequence variability.
