Аннотация
Purifying selection reduces genetic diversity, both at sites under direct selection and at
linked neutral sites. This process, known as background selection, is thought to play
an important role in shaping genomic diversity in natural populations. Yet despite
its importance, the effects of background selection are not fully understood. Previous
theoretical analyses of this process have taken a backwards-time approach based on
the structured coalescent. While they provide some insight, these methods are either
limited to very small samples or are computationally prohibitive. Here, we present a new
forward-time analysis of the trajectories of both neutral and deleterious mutations at a
nonrecombining locus. We find that strong purifying selection leads to remarkably rich
dynamics: neutral mutations can exhibit sweep-like behavior, and deleterious mutations
can reach substantial frequencies even when they are guaranteed to eventually go extinct.
Our analysis of these dynamics allows us to calculate analytical expressions for the full
site frequency spectrum. We find that whenever background selection is strong enough
to lead to a reduction in genetic diversity, it also results in substantial distortions to the
site frequency spectrum, which can mimic the effects of population expansions or positive
selection. Because these distortions are most pronounced in the low and high frequency
ends of the spectrum, they become particularly important in larger samples, but may
have small effects in smaller samples. We also apply our forward-time framework to
calculate other quantities, such as the ultimate fates of polymorphisms or the fitnesses
of their ancestral backgrounds
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