soft sweep - senecio7の日記

Sellis D, Callahan BJ, Petrov DA & Messer PW 2011 Heterozygote advantage as a natural consequence of adaptation in diploids. PNAS 108:20666-20671.

molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations
a substantial proportion of adaptive mutations should display heterozygote advantage
in diploids, adaptation should often proceed through a succession of short-lived balanced states that maintain substantially higher levels of phenotypic and fitness variation in the population compared with classic adaptive walks
in fast-changing environments, this variation produces a diversity advantage that allows diploids to remain better adapted compared with haploids despite the disadvantage associated with the presence of unfit homozygotes
the short-lived balanced states arising during adaptive walks should be mostly invisible to current scans for long-term balancing selection
they should leave signatures of incomplete selective sweeps, which do appear to be common in many species
balancing selection, as a natural consequence of frequent adaptation, might play a more prominent role among the forces maintaining genetic variation

adaptation might often involve mutations that have complex pleiotropic effects in an effectively multidimensional phenotypic space
the classic model that incorporates this key feature of adaptation is Fisher's geometric model

the larger range of adaptive mutations available to diploids comes with a catch
many of these adaptive mutations display heterozygote advantage, and thus will not simply go to fixation

adaptive walks in diploids typically involve the succession of many intermediate balanced polymorphisms that tend to be ephemeral
they are quickly displaced by new adaptive alleles, themselves often displaying heterozygote advantage
these dynamics contrast sharply to those in haploid populations, where adaptive walks proceed by successive sweeps of adaptive mutations and populations are generally monomorphic between sweeps

environmental changes that displace the phenotypic optimum can convert dominance variance of fitness into additive variance, which would then fuel adaptation

our finding that heterozygote advantage emerges naturally in Fisher's geometric model if mutations are sufficiently large is very robust to the details of the model
the number of dimensions
the choice of phenotypic dominance rules, including under-, over-, and incomplete dominance
mutation rate and size distribution
population size
flatness of the fitness function
the features that underlie pervasive heterozygote advantage in Fisher's model are also likely to apply very generally in nature

the classic model of adaptation holds that adaption is driven by adaptive mutations that sweep quickly to fixation
our model also predicts such fast fixation events
it additionally predicts that many adaptive mutations will initially only sweep to intermediate frequencies
they are then maintained for a period of time by balancing selection, before continuing on to either fixation or loss
we also expect the presence of many incomplete selective sweeps

the abundance of incomplete sweeps in natural and experimental populations is consistent with but, unfortunately, not uniquely predictive of adaptation-driven balancing selection
other scenarios, such as frequency-dependent selection, adaptation to specific subhabitats, and polygenic adaptation, also predict incomplete sweeps

we thus advocate that the balance theory of genetic variation should be given new life and reassessed using all the modern genomic tools at our disposal