Matthew Hartfield

Current hypotheses for the evolution of sex and recombination

The evolution of sex is one of the most important and controversial problems in evolutionary biology. Although sex is almost universal in higher animals and plants, its inherent costs have made its maintenance difficult to explain. The most famous of these is the twofold cost of males, which can greatly reduce the fecundity of a sexual population, compared to a population of asexual females. Over the past century, multiple hypotheses, along with experimental evidence to support these, have been put forward to explain widespread costly sex. In this review, we outline some of the most prominent theories, along with the experimental and observational evidence supporting these. Historically, there have been 4 classes of theories: the ability of sex to fix multiple novel advantageous mutants (Fisher-Muller hypothesis); sex as a mechanism to stop the build-up of deleterious mutations in finite populations (Mullers ratchet); recombination creating novel genotypes that can resist infection by parasites (Red Queen hypothesis); and the ability of sex to purge bad genomes if deleterious mutations act synergistically (mutational deterministic hypothesis). Current theoretical and experimental evidence seems to favor the hypothesis that sex breaks down selection interference between new mutants, or it acts as a mechanism to shuffle genotypes in order to repel parasitic invasion. However, there is still a need to collect more data from natural populations and experimental studies, which can be used to test different hypotheses.

RECOMBINATION AND HITCHHIKING OF DELETERIOUS ALLELES

When new advantageous alleles arise and spread within a population, deleterious alleles at neighboring loci can hitchhike alongside them and spread to fixation in areas of low recombination, introducing a fixed mutation load. We use branching processes and diffusion equations to calculate the probability that a deleterious allele hitchhikes and fixes alongside an advantageous mutant. As expected, the probability of fixation of a deleterious hitchhiker rises with the selective advantage of the sweeping allele and declines with the selective disadvantage of the deleterious hitchhiker. We then use computer simulations of a genome with an infinite number of loci to investigate the increase in load after an advantageous mutant is introduced. We show that the appearance of advantageous alleles on genetic backgrounds loaded with deleterious alleles has two potential effects: it can fix deleterious alleles, and it can facilitate the persistence of recombinant lineages that happen to occur. The latter is expected to reduce the signals of selection in the surrounding region. We consider these results in light of human genetic data to infer how likely it is that such deleterious hitchhikers have occurred in our recent evolutionary past.

The Role of Advantageous Mutations in Enhancing the Evolution of a Recombination Modifier

Although the evolution of recombination is still a major problem in evolutionary genetics, recent theoretical studies have shown that recombination can evolve by breaking down interference (“Hill–Robertson effects”) among multiple loci. This leads to selection on a recombination modifier in a population subject to recurrent deleterious mutation. Here, we use computer simulations to investigate the evolution of a recombination modifier under three different scenarios of recurrent mutation in a finite population: (1) mutations are deleterious only, (2) mutations are advantageous only, and (3) there is a mixture of deleterious and advantageous mutations. We also investigate how linkage disequilibrium, the strength of selection acting on a modifier, and effective population size change under the different scenarios. We observe that adding even a small number of advantageous mutations increases the fixation rate of modifiers that increase recombination, especially if the effects of deleterious mutations are weak. However, the strength of selection on a modifier is less than the summed strengths had there been deleterious mutations only and advantageous mutations only.

Evolutionary genetic consequences of facultative sex and outcrossing

Explaining the selective forces that underlie different reproductive modes forms a major part of evolution research. Many organisms are facultative sexuals, with the ability to reproduce both sexually and asexually. Reduced sequencing costs means it is now possible to start investigating genome sequences of a wider number of these organisms in depth, but teasing apart the genetic forces underlying the maintenance of facultative sexual reproduction remains a challenge. An analogous problem exists when determining the genetic consequences of a degree of outcrossing (and recombination) in otherwise self‐fertilizing organisms. Here, I provide an overview of existing research on the evolutionary basis behind different reproductive modes, with a focus on explaining the population genetic effects favouring low outcrossing rates in either partially selfing or asexual species. I review the outcomes that both self‐fertilization and asexuality have on either purging deleterious mutations or fixing beneficial alleles, and what empirical data exist to support these theories. In particular, a greater application of mathematical models to genomic data has provided insight into the numerous effects that transitions to self‐fertilization from outcrossing have on genetic architecture. Similar modelling approaches could be used to determine the forces shaping genetic diversity of facultative sexual species. Hence, a further unification of mathematical models with next‐generation sequence data will prove important in exploring the genetic influences on reproductive system evolution.

Hitchhiking of Deleterious Alleles and the Cost of Adaptation in Partially Selfing Species

Self-fertilization is generally seen to be disadvantageous in the long term. It increases genetic drift, which subsequently reduces polymorphism and the efficiency of selection, which also challenges adaptation. However, high selfing rates can increase the fixation probability of recessive beneficial mutations, but existing theory has generally not accounted for the effect of linked sites. Here, we analyze a model for the fixation probability of deleterious mutants that hitchhike with selective sweeps in diploid, partially selfing populations. Approximate analytical solutions show that, conditional on the sweep not being lost by drift, higher inbreeding rates increase the fixation probability of the deleterious allele, due to the resulting reduction in polymorphism and effective recombination. When extending the analysis to consider a distribution of deleterious alleles, as well as the average fitness increase after a sweep, we find that beneficial alleles generally need to be more recessive than the previously assumed dominance threshold (h < 1/2) for selfing to be beneficial from one-locus theory. Our results highlight that recombination aiding the efficiency of selection on multiple loci amplifies the fitness benefits of outcrossing over selfing, compared to results obtained from one-locus theory. This effect additionally increases the parameter range under which obligate outcrossing is beneficial over partial selfing.

Introducing the Outbreak Threshold in Epidemiology

When a pathogen is rare in a host population, there is a chance that it will die out because of stochastic effects instead of causing a major epidemic. Yet no criteria exist to determine when the pathogen increases to a risky level, from which it has a large chance of dying out, to when a major outbreak is almost certain. We introduce such an outbreak threshold (T0), and find that for large and homogeneous host populations, in which the pathogen has a reproductive ratio R0, on the order of 1/Log(R0) infected individuals are needed to prevent stochastic fade-out during the early stages of an epidemic. We also show how this threshold scales with higher heterogeneity and R0 in the host population. These results have implications for controlling emerging and re-emerging pathogens.

Coalescent Times and Patterns of Genetic Diversity in Species with Facultative Sex: Effects of Gene Conversion, Population Structure and Heterogeneity

Many diploid organisms undergo facultative sexual reproduction. However, little is currently known concerning the distribution of neutral genetic variation among facultative sexual organisms except in very simple cases. Understanding this distribution is important when making inferences about rates of sexual reproduction, effective population size, and demographic history. Here we extend coalescent theory in diploids with facultative sex to consider gene conversion, selfing, population subdivision, and temporal and spatial heterogeneity in rates of sex. In addition to analytical results for two-sample coalescent times, we outline a coalescent algorithm that accommodates the complexities arising from partial sex; this algorithm can be used to generate multisample coalescent distributions. A key result is that when sex is rare, gene conversion becomes a significant force in reducing diversity within individuals. This can reduce genomic signatures of infrequent sex (i.e., elevated within-individual allelic sequence divergence) or entirely reverse the predicted patterns. These models offer improved methods for assessing null patterns of molecular variation in facultative sexual organisms.

Epidemiological Feedbacks Affect Evolutionary Emergence of Pathogens

The evolutionary emergence of new pathogens via mutation poses a considerable risk to human and animal populations. Most previous studies have investigated cases where a potentially pandemic strain emerges though mutation from an initial maladapted strain (i.e., its basic reproductive ratio R0 < 1). However, an alternative (and arguably more likely) cause of novel pathogen emergence is where a “weakly adapted” strain (with R0 ≈ 1) mutates into a strongly adapted strain (with R0 ≫ 1). In this case, a proportion of the host susceptible population is removed as the first strain spreads, but the impact this feedback has on emergence of mutated strains has yet to be quantified. We produce a model of pathogen emergence that takes into account changes in the susceptible population over time and find that the ongoing depletion of susceptible individuals by the first strain has a drastic effect on the emergence probability of the mutated strain, above that assumed by just scaling the reproductive ratio. Finally, we apply our model to the documented emergence of Chikungunya virus on La Réunion Island and demonstrate that the emergence probability of the mutated strain was reduced approximately 10-fold, compared to models assuming that susceptible depletion would not affect outbreak probability. These results highlight the importance of taking population feedbacks into account when predicting disease emergence.

Coalescence with Background and Balancing Selection in Systems with Bi- and Uniparental Reproduction: Contrasting Partial Asexuality and Selfing.

Uniparental reproduction in diploids, via asexual reproduction or selfing, reduces the independence with which separate loci are transmitted across generations. This is expected to increase the extent to which a neutral marker is affected by selection elsewhere in the genome. Such effects have previously been quantified in coalescent models involving selfing. Here we examine the effects of background selection and balancing selection in diploids capable of both sexual and asexual reproduction (i.e., partial asexuality). We find that the effect of background selection on reducing coalescent time (and effective population size) can be orders of magnitude greater when rates of sex are low than when sex is common. This is because asexuality enhances the effects of background selection through both a recombination effect and a segregation effect. We show that there are several reasons that the strength of background selection differs between systems with partial asexuality and those with comparable levels of uniparental reproduction via selfing. Expectations for reductions in Ne via background selection have been verified using stochastic simulations. In contrast to background selection, balancing selection increases the coalescence time for a linked neutral site. With partial asexuality, the effect of balancing selection is somewhat dependent upon the mode of selection (e.g., heterozygote advantage vs. negative frequency-dependent selection) in a manner that does not apply to selfing. This is because the frequency of heterozygotes, which are required for recombination onto alternative genetic backgrounds, is more dependent on the pattern of selection with partial asexuality than with selfing.

Limits to Adaptation in Partially Selfing Species

In outcrossing populations, “Haldane’s sieve” states that recessive beneficial alleles are less likely to fix than dominant ones, because they are less exposed to selection when rare. In contrast, selfing organisms are not subject to Haldane’s sieve and are more likely to fix recessive types than outcrossers, as selfing rapidly creates homozygotes, increasing overall selection acting on mutations. However, longer homozygous tracts in selfers also reduce the ability of recombination to create new genotypes. It is unclear how these two effects influence overall adaptation rates in partially selfing organisms. Here, we calculate the fixation probability of beneficial alleles if there is an existing selective sweep in the population. We consider both the potential loss of the second beneficial mutation if it has a weaker advantage than the first one, and the possible replacement of the initial allele if the second mutant is fitter. Overall, loss of weaker adaptive alleles during a first selective sweep has a larger impact on preventing fixation of both mutations in highly selfing organisms. Furthermore, the presence of linked mutations has two opposing effects on Haldane’s sieve. First, recessive mutants are disproportionally likely to be lost in outcrossers, so it is likelier that dominant mutations will fix. Second, with elevated rates of adaptive mutation, selective interference annuls the advantage in selfing organisms of not suffering from Haldane’s sieve; outcrossing organisms are more able to fix weak beneficial mutations of any dominance value. Overall, weakened recombination effects can greatly limit adaptation in selfing organisms.