polygenic adaptation - senecio7の日記

Pavlidis P, Metzler D & Stephan W 2012 Selective sweeps in multilocus models of quantitative traits. Genetics, in press.
doi:10.1534/genetics.112.142547

we study the trajectory of an allele that affects a polygenic trait selected towards a phenotypic optimum
we examine the well-characterized two-locus two-allele model
we also provide results for diallelic models with up to eight loci
when the optimum phenotype is that of the double heterozygote in a two-locus model, and there is no dominance or epistasis of effects on the trait, the trajectories of selected mutations rarely reach fixation
instead, a polymorphic equilibrium at both loci is approached
increasing the number of loci decreases the probability of fixation
multi-locus response to selection may in some cases prevent selective sweeps from being completed
conditions causing this to happen strongly depend on the genetic architecture of the trait
fixation of selected mutations is likely in many instances

we focus on stabilizing selection, which drives a trait towards a phenotypic optimum
we are particularly interested in exploring the parameter range of trajectories that fix and therefore might generate selective sweeps

there have been a great interest in the maintenance of genetic variability under stabilizing selection
stabilizing selection is assumed to operate on traits in various organisms
this type of selection exhausts genetic variation
many quantitative traits exhibit high levels of genetic variability
a lot of work has been devoted to exploring the ability of stabilizing selection in maintaining genetic variability of quantitative traits that are controlled by multiple loci in the absence of mutation
theoretical focus was mainly on two-locus models
also models of more than two loci have been analyzed
the two-locus model predicts that genetic variability may remain in the population due to stabilizing selection per se
in models with more than two loci the amount of genetic variability maintained by stabilizing selection is smaller

for the two-locus model, ... it has been shown that there are nine equilibria (Bürger 2000), seven of which can be stable but not simultaneously
they can be either polymorphic for both loci, one of them, or totally monomorphic

the first effort that bridges quantitative trait evolution and selective sweeps was made by Chevin and Hospital (2008)
Chevin and Hospital (2008) used Lande's model to infer the deterministic trajectory of a beneficial mutation that affects a quantitative trait in the presence of background genetic variability
in the case of stabilizing selection their approach (based on Lande's model) suggests that the occurrence of selective sweeps at quantitative trait loci (QTL) is expected to be very rare
the present study assumes an explicit number of loci that determine the trait
the assumption of constant variability in the genetic background is relaxed since the genetic background is modeled explicitly
we analyze the evolution of deterministic multi-locus model and also its stochastic analog assuming a finite constant effective size
we also examine the parameters (such as the recombination rate and the contribution of the alleles to the phenotype) that affect the fixation probability of the new mutation
conditioning on the trajectory we generate coalescent simulations and examine the properties of the genealogy and the associated polymorphism patterns

there is no dominance of allelic effects on the trait
but there may be for their effects on fitness
due to the fitness function the effects of the alleles on fitness are not additive

we are particularly interested in the work of Willensdorfer and Bürger (2003) who explore the equilibrium properties of the two-locus two-allele model for Gaussian selection

a neutral allele may be under the hitchhiking effects of two (or more) selected loci
simulating the genealogy of a neutral site would require tracking the frequencies of all gametes backward in time instead of tracking the frequency of a single allele
such an analysis is beyond the goals of the present article
this approach yields reliable results in a close neighborhood of the sweep for cases of relatively weak selection and weakly linked loci

for a given trajectory, 1000 coalescent simulations are performed

when the trajectories do not reach fixation, then a part or all signatures of a selective sweep become invisible, depending on the equilibrium frequency of the trajectory
a large fraction of trajectories is maintained at some equilibrium value and does not reach fixation
for these trajectories analysis of incomplete sweeps ... may be useful

there is, however, an essential difference between incomplete sweeps and sweeps in multi-locus models that were studied in this article
incomplete sweeps are on the way to fixation, whereas the sweeps studied here remain at equilibrium frequency
the signatures of selection will be visible only in the cases in which the equilibrium frequency has been reached recently
if the trajectory remained at the equilibrium level (either polymorphic or monomorphic for the focal allele) for too long, then the signatures of selection will fade away due to recombination

the statistical tools that have been developed to detect selective sweeps may detect only a small proportion of the multi-locus selection cases
namely only those cases that result in fixed trajectories or equilibrium trajectories close to fixation
tools that are used for detecting incomplete sweeps may be useful when the trajectory has reached its equilibrium frequency very recently