TL;DR: A hierarchical‐Bayesian method is developed, implemented via Markov chain Monte Carlo (MCMC), and its performance is assessed in distinguishing the loci simulated under selection from the neutral loci, finding that both methods can identify loci subject to adaptive selection when the selection coefficient is at least five times the migration rate.
Abstract: The identification of signatures of natural selection in genomic surveys has become an area of intense research, stimulated by the increasing ease with which genetic markers can be typed. Loci identified as subject to selection may be functionally important, and hence (weak) candidates for involvement in disease causation. They can also be useful in determining the adaptive differentiation of populations, and exploring hypotheses about speciation. Adaptive differentiation has traditionally been identified from differences in allele frequencies among different populations, summarised by an estimate of FST. Low outliers relative to an appropriate neutral population-genetics model indicate loci subject to balancing selection, whereas high outliers suggest adaptive (directional) selection. However, the problem of identifying statistically significant departures from neutrality is complicated by confounding effects on the distribution of FST estimates, and current methods have not yet been tested in large-scale simulation experiments. Here, we simulate data from a structured population at many unlinked, diallelic loci that are predominantly neutral but with some loci subject to adaptive or balancing selection. We develop a hierarchical-Bayesian method, implemented via Markov chain Monte Carlo (MCMC), and assess its performance in distinguishing the loci simulated under selection from the neutral loci. We also compare this performance with that of a frequentist method, based on moment-based estimates of FST. We find that both methods can identify loci subject to adaptive selection when the selection coefficient is at least five times the migration rate. Neither method could reliably distinguish loci under balancing selection in our simulations, even when the selection coefficient is twenty times the migration rate.
TL;DR: This work uses diffusion theory to calculate the probabilities for selective adaptations and finds a large increase in the fixation probability for weak substitutions, if alleles originate from the standing genetic variation.
Abstract: A population can adapt to a rapid environmental change or habitat expansion in two ways. It may adapt either through new beneficial mutations that subsequently sweep through the population or by using alleles from the standing genetic variation. We use diffusion theory to calculate the probabilities for selective adaptations and find a large increase in the fixation probability for weak substitutions, if alleles originate from the standing genetic variation. We then determine the parameter regions where each scenario—standing variation vs . new mutations—is more likely. Adaptations from the standing genetic variation are favored if either the selective advantage is weak or the selection coefficient and the mutation rate are both high. Finally, we analyze the probability of “soft sweeps,” where multiple copies of the selected allele contribute to a substitution, and discuss the consequences for the footprint of selection on linked neutral variation. We find that soft sweeps with weaker selective footprints are likely under both scenarios if the mutation rate and/or the selection coefficient is high.
TL;DR: The traditional gradualist scheme of weak selection acting on polygenic variation should be supplemented by the view that adaptation is often based on oligogenic variation exposed to commonplace, strong, fluctuating natural selection.
Abstract: Darwin insisted that evolutionary change occurs very slowly over long periods of time, and this gradualist view was accepted by his supporters and incorporated into the infinitesimal model of quantitative genetics developed by R. A. Fisher and others. It dominated the first century of evolutionary biology, but has been challenged in more recent years both by field surveys demonstrating strong selection in natural populations and by quantitative trait loci and genomic studies, indicating that adaptation is often attributable to mutations in a few genes. The prevalence of strong selection seems inconsistent, however, with the high heritability often observed in natural populations, and with the claim that the amount of morphological change in contemporary and fossil lineages is independent of elapsed time. I argue that these discrepancies are resolved by realistic accounts of environmental and evolutionary changes. First, the physical and biotic environment varies on all time-scales, leading to an indefinite increase in environmental variance over time. Secondly, the intensity and direction of natural selection are also likely to fluctuate over time, leading to an indefinite increase in phenotypic variance in any given evolving lineage. Finally, detailed long-term studies of selection in natural populations demonstrate that selection often changes in direction. I conclude that the traditional gradualist scheme of weak selection acting on polygenic variation should be supplemented by the view that adaptation is often based on oligogenic variation exposed to commonplace, strong, fluctuating natural selection.
TL;DR: Analytical models for mutation accumulation that obviate the need for time‐consuming computer simulations in certain ranges of the parameter space are developed and it is shown that an intermediate selection coefficient minimizes the time to extinction.
Abstract: We extend our earlier work on the role of deleterious mutations in the extinction of obligately asexual populations. First, we develop analytical models for mutation accumulation that obviate the need for time-consuming computer simulations in certain ranges of the parameter space. When the number of mutations entering the population each generation is fairly high, the number of mutations per individual and the mean time to extinction can be predicted using classical approaches in quantitative genetics. However, when the mutation rate is very low, a fixation-probability approach is quite effective. Second, we show that an intermediate selection coefficient (s) minimizes the time to extinction. The critical value of s can be quite low, and we discuss the evolutionary implications of this, showing that increased sensitivity to mutation and loss of capacity for DNA repair can be selectively advantageous in asexual organisms. Finally, we consider the consequences of the mutational meltdown for the extinction of mitochondrial lineages in sexual species.
TL;DR: A theoretical model is described to treat both aspects of interference in large populations of large asexual populations and finds that the effective selection coefficient exactly coincides with the most common fixed mutational effect.
Abstract: When large asexual populations adapt, competition between simultaneously segregating mutations slows the rate of adaptation and restricts the set of mutations that eventually fix. This phenomenon of interference arises from competition between mutations of different strengths as well as competition between mutations that arise on different fitness backgrounds. Previous work has explored each of these effects in isolation, but the way they combine to influence the dynamics of adaptation remains largely unknown. Here, we describe a theoretical model to treat both aspects of interference in large populations. We calculate the rate of adaptation and the distribution of fixed mutational effects accumulated by the population. We focus particular attention on the case when the effects of beneficial mutations are exponentially distributed, as well as on a more general class of exponential-like distributions. In both cases, we show that the rate of adaptation and the influence of genetic background on the fixation of new mutants is equivalent to an effective model with a single selection coefficient and rescaled mutation rate, and we explicitly calculate these effective parameters. We find that the effective selection coefficient exactly coincides with the most common fixed mutational effect. This equivalence leads to an intuitive picture of the relative importance of different types of interference effects, which can shift dramatically as a function of the population size, mutation rate, and the underlying distribution of fitness effects.