polygenic adaptation - senecio7の日記

Desai MM, Walczak AM & Fisher DS 2013 Genetic diversity and the structure of genealogies in rapidly adapting populations. Genetics 193:565-585.

hard selective sweeps are the primary mode of adaptation in small- to moderate-sized populations in which beneficial mutations are sufficiently rare
in larger populations where beneficial mutations occur more frequently, many different mutant lineages can segregate simultaneously in the population
if the loci involved are sufficiently distant that recombination occurs frequently enough between them, their fates are independent and adaptation will proceed via independent hard sweeps at each locus
in largely asexual organisms such as microbes and viruses, and on shorter distance scales within sexual genomes, selective sweeps at linked loci can overlap and interfere with one another

we consider instead a case more analogous to models in quantitative genetics, where selection acts on a large number of loci that all affect fitness
our analysis of clonal interference can be thought of as a description of polygenic adaptation, where selection favors the individuals who have beneficial alleles at multiple loci
recent work has argued for the potential importance of polygenic adaptation from standing genetic variation ..., loosely analogous to the case where soft sweeps act at many loci
our analysis in this article, by contrast, describes polygenic adaptation via multiple new mutations of similar effect at many loci, where each locus has a low enough mutation rate that it would undergo a hard sweep in the absence of the other loci

mutations at the many loci occur and segregate simultaneously, interfering with each others' fixation
since the mutations occur at different sites, multiple beneficial mutations can also occur in the same genetic background and hitchhike together

our work here focuses entirely on asexual populations or on diversity within a short genomic region that remains perfectly linked over the relevant time scales
in the opposite case of strong recombination, adaptation will progress via independent hard selective sweeps at each selected locus
further work is required to understand the effects of intermediate levels of recombination, where the approach recently introduced by Neher et al. (2010) may provide a useful starting point

there is no epistasis for fitness
the fitness of an individual with k beneficial mutations is w_k = (1 + s)^k ≈ 1 + sk

this model is the simplest framework that captures the effects of positive selection on a large number of independent loci of similar effect
there is first a transient phase while variation at these loci initially increases
there is then a steady-state phase during which the population continuously adapts toward higher fitness
adaptation will eventually slow down as the population approaches a well-adapted state
we focus on the second phase of rapid and continuous adaptation

we have assumed that epistatic interactions between mutations can be neglected and that the total potential supply of beneficial mutations is not significantly depleted over the course of adaptation