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.     

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.     

Population persistence under high mutation rate: From evolutionary rescue to lethal mutagenesis

Populations may genetically adapt to severe stress that would otherwise cause their extirpation. Recent theoretical work, combining stochastic demography with Fisher's geometric model of adaptation, has shown how evolutionary rescue becomes unlikely beyond some critical intensity of stress. Increasing mutation rates may however allow adaptation to more intense stress, raising concerns about the effectiveness of treatments against pathogens. This previous work assumes that populations are rescued by the rise of a single resistance mutation. However, even in asexual organisms, rescue can also stem from the accumulation of multiple mutations in a single genome. Here, we extend previous work to study the rescue process in an asexual population where the mutation rate is sufficiently high so that such events may be common. We predict both the ultimate extinction probability of the population and the distribution of extinction times. We compare the accuracy of different approximations covering a large range of mutation rates. Moderate increase in mutation rates favors evolutionary rescue. However, larger increase leads to extinction by the accumulation of a large mutation load, a process called lethal mutagenesis. We discuss how these results could help design “evolution‐proof” antipathogen treatments that even highly mutable strains could not overcome.     

Higher intensity of purifying selection on >90% of the human genes revealed by the intrinsic replacement mutation rates

For over 3 decades, the rate of replacement mutations has been assumed to be equal to, and estimated from, the rate of "strictly" neutral sequence divergence in noncoding regions and in silent-codon positions where mutations do not alter the amino acid encoded. This assumption is fundamental to estimating the fraction of harmful protein mutations and to identifying adaptive evolution at individual codons and proteins. We show that the assumption is not justifiable because a much larger fraction of codon positions is involved in hypermutable CpG dinucleotides as compared with the introns, leading to a higher expected replacement mutation rate per site in a vast majority of the genes. Consideration of this difference reveals a higher intensity of purifying natural selection than previously inferred in human genes. We also show that a much smaller number of genes are expected to be evolving with positive selection than that predicted using sequence divergence at intron and silent positions in the human genome. These patterns indicate the need for using new approaches for estimating rates of amino acid-altering mutations in order to find positively selected genes and codons in genomes that contain hypermutable CpG's.     

Evidence for convergent nucleotide evolution and high allelic turnover rates at the complementary sex determiner gene of Western and Asian honeybees

Our understanding of the impact of recombination, mutation, genetic drift, and selection on the evolution of a single gene is still limited. Here we investigate the impact of all these evolutionary forces at the complementary sex determiner (csd) gene that evolves under a balancing mode of selection. Females are heterozygous at the csd gene and males are hemizygous; diploid males are lethal and occur when csd is homozygous. Rare alleles thus have a selective advantage, are seldom lost by the effect of genetic drift, and are maintained over extended periods of time when compared with neutral polymorphisms. Here, we report on the analysis of 17, 19, and 15 csd alleles of Apis cerana, Apis dorsata, and Apis mellifera honeybees, respectively. We observed great heterogeneity of synonymous (piS) and nonsynonymous (piN) polymorphisms across the gene, with a consistent peak in exons 6 and 7. We propose that exons 6 and 7 encode the potential specifying domain (csd-PSD) that has accumulated elevated nucleotide polymorphisms over time by balancing selection. We observed no direct evidence that balancing selection favors the accumulation of nonsynonymous changes at csd-PSD (piN/piS ratios are all <1, ranging from 0.6 to 0.95). We observed an excess of shared nonsynonymous changes, which suggest that strong evolutionary constraints are operating at csd-PSD resulting in the independent accumulation of the same nonsynonymous changes in different alleles across species (convergent evolution). Analysis of csd-PSD genealogy revealed relatively short average coalescence times ( approximately 6 Myr), low average synonymous nucleotide diversity (piS < 0.09), and a lack of trans-specific alleles that substantially contrasts with previously analyzed loci under strong balancing selection. We excluded the possibility of a burst of diversification after population bottlenecking and intragenic recombination as explanatory factors, leaving high turnover rates as the explanation for this observation. By comparing observed allele richness and average coalescence times with a simplified model of csd-coalescence, we found that small long-term population sizes (i.e., N(e) < 10(4)), but not high mutation rates, can explain short maintenance times, implicating a strong historical impact of genetic drift on the molecular evolution of highly social honeybees.     

Persistence of the single lineage of transmissible 'social cancer' in an asexual ant

How cooperation can arise and persist, given the threat of cheating phenotypes, is a central problem in evolutionary biology, but the actual significance of cheating in natural populations is still poorly understood. Theories of social evolution predict that cheater lineages are evolutionarily short-lived. However, an exception comes from obligate socially parasitic species, some of which thought to have arisen as cheaters within cooperator colonies and then diverged through sympatric speciation. This process requires the cheater lineage to persist by avoiding rapid extinction that would result from the fact that the cheaters inflict fitness cost on their host. We examined whether this prerequisite is fulfilled, by estimating the persistence time of cheaters in a field population of the parthenogenetic ant Pristomyrmex punctatus. Population genetic analysis found that the cheaters belong to one monophyletic lineage which we infer has persisted for 200-9200 generations. We show that the cheaters migrate and are thus horizontally transmitted between colonies, a trait allowing the lineage to avoid rapid extinction with its host colony. Although horizontal transmission of disruptive cheaters has the potential to induce extinction of the entire population, such collapse is likely averted when there is spatially restricted migration in a structured population, a scenario that matches the observed isolation by distance pattern that we found. We compare our result with other examples of disruptive and horizontally transmissible cheater lineages in nature.     

The prediction of adaptive evolution: empirical application of the secondary theorem of selection and comparison to the breeder's equation

Adaptive evolution occurs when fitness covaries with genetic merit for a trait (or traits). The breeder's equation (BE), in both its univariate and multivariate forms, allows us to predict this process by combining estimates of selection on phenotype with estimates of genetic (co)variation. However, predictions are only valid if all factors causal for trait-fitness covariance are measured. Although this requirement will rarely (if ever) be met in practice, it can be avoided by applying Robertson's secondary theorem of selection (STS). The STS predicts evolution by directly estimating the genetic basis of trait-fitness covariation without any explicit model of selection. Here we apply the BE and STS to four morphological traits measured in Soay sheep (Ovis aries) from St. Kilda. Despite apparently positive selection on heritable size traits, sheep are not getting larger. However, although the BE predicts increasing size, the STS does not, which is a discrepancy that suggests unmeasured factors are upwardly biasing our estimates of selection on phenotype. We suggest this is likely to be a general issue, and that wider application of the STS could offer at least a partial resolution to the common discrepancy between naive expectations and observed trait dynamics in natural populations.     

Differences in parasite susceptibility and costs of resistance between naturally exposed and unexposed host populations

It is generally assumed that resistance to parasitism entails costs. Consequently, hosts evolving in the absence of parasites are predicted to invest less in costly resistance mechanisms than hosts consistently exposed to parasites. This prediction has, however, rarely been tested in natural populations. We studied the susceptibility of three naïve, three parasitized and one recently isolated Asellus aquaticus isopod populations to an acanthocephalan parasite. We found that parasitized populations, with the exception of the isopod population sympatric with the parasite strain used, were less susceptible to the parasite than the naïve populations. Exposed but uninfected (resistant) isopods from naïve populations, but not from parasitized populations, exhibited greater mortality than controls, implying that resistance entails survival costs primarily for naïve isopods. These results suggest that parasites can drive the evolution of host resistance in the wild, and that co‐existence with parasites may increase the cost‐effectiveness of defence mechanisms.