Model and test in a fungus of the probability that beneficial mutations survive drift

Determining the probability of fixation of beneficial mutations is critically important for building predictive models of adaptive evolution. Despite considerable theoretical work, models of fixation probability have stood untested for nearly a century. However, recent advances in experimental and theoretical techniques permit the development of models with testable predictions. We developed a new model for the probability of surviving genetic drift, a major component of fixation probability, for novel beneficial mutations in the fungus Aspergillus nidulans, based on the life-history characteristics of its colony growth on a solid surface. We tested the model by measuring the probability of surviving drift in 11 adapted strains introduced into wild-type populations of different densities. We found that the probability of surviving drift increased with mutant invasion fitness, and decreased with wild-type density, as expected. The model accurately predicted the survival probability for the majority of mutants, yielding one of the first direct tests of the extinction probability of beneficial mutations.     

Adaptation,Clonal Interference,and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli

Twelve replicate populations of Escherichia coli have been evolving in the laboratory for >25 years and 60,000 generations. We analyzed bacteria from whole-population samples frozen every 500 generations through 20,000 generations for one well-studied population, called Ara−1. By tracking 42 known mutations in these samples, we reconstructed the history of this population’s genotypic evolution over this period. The evolutionary dynamics of Ara−1 show strong evidence of selective sweeps as well as clonal interference between competing lineages bearing different beneficial mutations. In some cases, sets of several mutations approached fixation simultaneously, often conveying no information about their order of origination; we present several possible explanations for the existence of these mutational cohorts. Against a backdrop of rapid selective sweeps both earlier and later, two genetically diverged clades coexisted for >6000 generations before one went extinct. In that time, many additional mutations arose in the clade that eventually prevailed. We show that the clades evolved a frequency-dependent interaction, which prevented the immediate competitive exclusion of either clade, but which collapsed as beneficial mutations accumulated in the clade that prevailed. Clonal interference and frequency dependence can occur even in the simplest microbial populations. Furthermore, frequency dependence may generate dynamics that extend the period of coexistence that would otherwise be sustained by clonal interference alone.     

Limits to adaptation in asexual populations

In asexual populations, the rate of adaptation is basically limited by the frequency and properties of spontaneous beneficial mutations. Hence, knowledge of these mutational properties and how they are affected by particular evolutionary conditions is a precondition for understanding the process of adaptation. Here, we address how the rate of adaptation of asexual populations is limited by its population size and mutation rate, as well as by two factors affecting the fraction of mutations that confer a benefit, i.e. the initial adaptedness of the population and the variability of the environment. These factors both influence which mutations are likely to occur, as well as the probability that they will ultimately contribute to adaptation. We attempt to separate the consequences of these basic population features in terms of their effect on the rate of adaptation by using results from evolution experiments with microorganisms.     

Establishment of new mutations in changing environments

Understanding adaptation in changing environments is an important topic in evolutionary genetics, especially in the light of climatic and environmental change. In this work, we study one of the most fundamental aspects of the genetics of adaptation in changing environments: the establishment of new beneficial mutations. We use the framework of time-dependent branching processes to derive simple approximations for the establishment probability of new mutations assuming that temporal changes in the offspring distribution are small. This approach allows us to generalize Haldane's classic result for the fixation probability in a constant environment to arbitrary patterns of temporal change in selection coefficients. Under weak selection, the only aspect of temporal variation that enters the probability of establishment is a weighted average of selection coefficients. These weights quantify how much earlier generations contribute to determining the establishment probability compared to later generations. We apply our results to several biologically interesting cases such as selection coefficients that change in consistent, periodic, and random ways and to changing population sizes. Comparison with exact results shows that the approximation is very accurate.     

The genetic basis of parallel and divergent phenotypic responses in evolving populations of Escherichia coli

Pleiotropy plays a central role in theories of adaptation, but little is known about the distribution of pleiotropic effects associated with different adaptive mutations. Previously, we described the phenotypic effects of a collection of independently arising beneficial mutations in Escherichia coli. We quantified their fitness effects in the glucose environment in which they evolved and their pleiotropic effects in five novel resource environments. Here we use a candidate gene approach to associate the phenotypic effects of the mutations with the underlying genetic changes. Among our collection of 27 adaptive mutants, we identified a total of 21 mutations (18 of which were unique) encompassing five different loci or gene regions. There was limited resolution to distinguish among loci based on their fitness effects in the glucose environment, demonstrating widespread parallelism in the direct response to selection. However, substantial heterogeneity in mutant effects was revealed when we examined their pleiotropic effects on fitness in the five novel environments. Substitutions in the same locus clustered together phenotypically, indicating concordance between molecular and phenotypic measures of divergence.     

Clonal interference is alleviated by high mutation rates in large populations

When a beneficial mutation is fixed in a population that lacks recombination, the genetic background linked to that mutation is fixed. As a result, beneficial mutations on different backgrounds experience competition, or "clonal interference," that can cause asexual populations to evolve more slowly than their sexual counterparts. Factors such as a large population size (N) and high mutation rates (mu) increase the number of competing beneficial mutations, and hence are expected to increase the intensity of clonal interference. However, recent theory suggests that, with very large values of Nmu, the severity of clonal interference may instead decline. The reason is that, with large Nmu, genomes including both beneficial mutations are rapidly created by recurrent mutation, obviating the need for recombination. Here, we analyze data from experimentally evolved asexual populations of a bacteriophage and find that, in these nonrecombining populations with very large Nmu, recurrent mutation does appear to ameliorate this cost of asexuality.     

The red queen coupled with directional selection favours the evolution of sex

Why sexual reproduction has evolved to be such a widespread mode of reproduction remains a major question in evolutionary biology. Although previous studies have shown that increased sex and recombination can evolve in the presence of host-parasite interactions (the 'Red Queen hypothesis' for sex), many of these studies have assumed that multiple loci mediate infection vs. resistance. Data suggest, however, that a major locus is typically involved in antigen presentation and recognition. Here, we explore a model where only one locus mediates host-parasite interactions, but a second locus is subject to directional selection. Even though the effects of these genes on fitness are independent, we show that increased rates of sex and recombination are favoured at a modifier gene that alters the rate of genetic mixing. This result occurs because of selective interference in finite populations (the 'Hill-Robertson effect'), which also favours sex. These results suggest that the Red Queen hypothesis may help to explain the evolution of sex by contributing a form of persistent selection, which interferes with directional selection at other loci and thereby favours sex and recombination.     

Adaptive evolution in a spatially structured asexual population

We study the process of adaptation in a spatially structured asexual haploid population. The model assumes a local competition for replication, where each organism interacts only with its nearest neighbors. We observe that the substitution rate of beneficial mutations is smaller for a spatially structured population than that seen for populations without structure. The difference between structured and unstructured populations increases as the adaptive mutation rate increases. Furthermore, the substitution rate decreases as the number of neighbors for local competition is reduced. We have also studied the impact of structure on the distribution of adaptive mutations that fix during adaptation.     

On the potential for evolutionary change in meristematic cell lineages through intraorganismal selection

In the absence of sexual recombination somatic mutations represent the only source of genetic variation in clonally propagating plants. We analyse the probability of such somatic mutations in the shoot apical meristem being fixed in descendant generations of meristems. A model of meristem cell dynamics is presented for the unstratified shoot apical meristem. The fate of one mutant initial is studied for a two- and three-celled shoot apical meristem. The main parameters of the model are the number of apical initials, the time between selection cycles, number of selection cycles and cell viability of the mutant genotype. As the number of mitotic divisions per selection cycle and number of selection cycles increases the chimeric state dissipates and the probability of mutation fixation approaches an asymptote. The value of this fixation asymptote depends primarily on cell viability, while the time to reach it is mainly influenced by the total number of mitotic divisions as well as the number of initials. In contrast to the presumed operation of Muller’s Ratchet in plants the chimeric state may represent an opportunity for deleterious mutations to be eliminated through intraorganismal selection or random drift. We conclude that intraorganismal selection not only can be a substantial force for the elimination of deleterious mutations, but also can have the potential to confer an evolutionary change through a meristematic cell lineage alone.