Selection on modifiers of genetic architecture under migration load.

Gene flow between populations adapting to differing local environmental conditions might be costly because individuals can disperse to habitats where their survival is low or because they can reproduce with locally maladapted individuals. The amount by which the mean relative population fitness is kept below one creates an opportunity for modifiers of the genetic architecture to spread due to selection. Prior work that separately considered modifiers changing dispersal, recombination rates, or altering dominance or epistasis, has typically focused on the direction of selection rather than its absolute magnitude. We here develop methods to determine the strength of selection on modifiers of the genetic architecture, including modifiers of the dispersal rate, in populations that have previously evolved local adaptation. We consider scenarios with up to five loci contributing to local adaptation and derive a new model for the deterministic spread of modifiers. We find that selection for modifiers of epistasis and dominance is stronger than selection for decreased recombination, and that selection for partial reductions in recombination are extremely weak, regardless of the number of loci contributing to local adaptation. The spread of modifiers that reduce dispersal depends on the number of loci, epistasis and extent of local adaptation in the ancestral population. We identify a novel effect, that modifiers of dominance are more strongly selected when they are unlinked to the locus that they modify. These findings help explain population differentiation and reproductive isolation and provide a benchmark to compare selection on modifiers under finite population sizes and demographic stochasticity.

The genomic basis of Red Queen dynamics during rapid reciprocal host-pathogen coevolution.

Red Queen dynamics, involving coevolutionary interactions between species, are ubiquitous, shaping the evolution of diverse biological systems. To date, information on the underlying selection dynamics and the involved genome regions is mainly available for bacteria-phage systems or only one of the antagonists of a eukaryotic host-pathogen interaction. We add to our understanding of these important coevolutionary interactions using an experimental host-pathogen model, which includes the nematode Caenorhabditis elegans and its pathogen Bacillus thuringiensis We combined experimental evolution with time-shift experiments, in which a focal host or pathogen is tested against a coevolved antagonist from the past, present, or future, followed by genomic analysis. We show that (i) coevolution occurs rapidly within few generations, (ii) temporal coadaptation at the phenotypic level is found in parallel across replicate populations, consistent with antagonistic frequency-dependent selection, (iii) genomic changes in the pathogen match the phenotypic pattern and include copy number variations of a toxin-encoding plasmid, and (iv) host genomic changes do not match the phenotypic pattern and likely involve selective responses at more than one locus. By exploring the dynamics of coevolution at the phenotypic and genomic level for both host and pathogen simultaneously, our findings demonstrate a more complex model of the Red Queen, consisting of distinct selective processes acting on the two antagonists during rapid and reciprocal coadaptation.

Slower environmental change hinders adaptation from standing genetic variation.

Evolutionary responses to environmental change depend on the time available for adaptation before environmental degradation leads to extinction. Explicit tests of this relationship are limited to microbes where adaptation usually depends on the sequential fixation of de novo mutations, excluding standing variation for genotype-by-environment fitness interactions that should be key for most natural species. For natural species evolving from standing genetic variation, adaptation at slower rates of environmental change may be impeded since the best genotypes at the most extreme environments can be lost during evolution due to genetic drift or founder effects. To address this hypothesis, we perform experimental evolution with self-fertilizing populations of the nematode Caenorhabditis elegans and develop an inference model to describe natural selection on extant genotypes under environmental change. Under a sudden environmental change, we find that selection rapidly increases the frequency of genotypes with high fitness in the most extreme environment. In contrast, under a gradual environmental change selection first favors genotypes that are worse at the most extreme environment. We demonstrate with a second set of evolution experiments that, as a consequence of slower environmental change and thus longer periods to reach the most extreme environments, genetic drift and founder effects can lead to the loss of the most beneficial genotypes. We further find that maintenance of standing genetic variation can retard the fixation of the best genotypes in the most extreme environment because of interference between them. Taken together, these results show that slower environmental change can hamper adaptation from standing genetic variation and they support theoretical models indicating that standing variation for genotype-by-environment fitness interactions critically alters the pace and outcome of adaptation under environmental change.

How differing modes of non-genetic inheritance affect population viability in fluctuating environments.

Different modes of non-genetic inheritance are expected to affect population persistence in fluctuating environments. We here analyse Caenorhabditis elegans density-independent per capita growth rate time series on 36 populations experiencing six controlled sequences of challenging oxygen level fluctuations across 60 generations, and parameterise competing models of non-genetic inheritance in order to explain observed dynamics. Our analysis shows that phenotypic plasticity and anticipatory maternal effects are sufficient to explain growth rate dynamics, but that a carryover model where 'epigenetic' memory is imperfectly transmitted and might be reset at each generation is a better fit to the data. We further find that this epigenetic memory is asymmetric since it is kept for longer when populations are exposed to the more challenging environment. Our analysis suggests that population persistence in fluctuating environments depends on the non-genetic inheritance of phenotypes whose expression is regulated across multiple generations.

Adaptation to Temporally Fluctuating Environments by the Evolution of Maternal Effects.

All organisms live in temporally fluctuating environments. Theory predicts that the evolution of deterministic maternal effects (i.e., anticipatory maternal effects or transgenerational phenotypic plasticity) underlies adaptation to environments that fluctuate in a predictably alternating fashion over maternal-offspring generations. In contrast, randomizing maternal effects (i.e., diversifying and conservative bet-hedging), are expected to evolve in response to unpredictably fluctuating environments. Although maternal effects are common, evidence for their adaptive significance is equivocal since they can easily evolve as a correlated response to maternal selection and may or may not increase the future fitness of offspring. Using the hermaphroditic nematode Caenorhabditis elegans, we here show that the experimental evolution of maternal glycogen provisioning underlies adaptation to a fluctuating normoxia-anoxia hatching environment by increasing embryo survival under anoxia. In strictly alternating environments, we found that hermaphrodites evolved the ability to increase embryo glycogen provisioning when they experienced normoxia and to decrease embryo glycogen provisioning when they experienced anoxia. At odds with existing theory, however, populations facing irregularly fluctuating normoxia-anoxia hatching environments failed to evolve randomizing maternal effects. Instead, adaptation in these populations may have occurred through the evolution of fitness effects that percolate over multiple generations, as they maintained considerably high expected growth rates during experimental evolution despite evolving reduced fecundity and reduced embryo survival under one or two generations of anoxia. We develop theoretical models that explain why adaptation to a wide range of patterns of environmental fluctuations hinges on the existence of deterministic maternal effects, and that such deterministic maternal effects are more likely to contribute to adaptation than randomizing maternal effects.

What Kind of Maternal Effects Can Be Selected For in Fluctuating Environments?

Just as phenotypic plasticity can evolve when developing individuals get informational cues about their future adult environment, deterministic maternal effects, where offspring trait values depend on the maternal environment, can evolve when mothers gain reliable information about the environments their offspring will face. Randomizing maternal effects (a type of diversifying bet hedging), where offspring trait values are randomized, can evolve by natural selection even when information about future environments is unavailable. We investigate selection on both randomizing and deterministic maternal effects in environments that show correlated fluctuations between two environmental states. We compare the strength of selection for deterministic and randomizing maternal effects and explicitly consider maternal fitness costs of producing offspring with different phenotypes. Only a small set of environmental parameters allow randomizing maternal effects to outcompete deterministic maternal effects; not only must there be little or no information available about future environments, but the frequency of each environment must fall within a narrow range. By contrast, deterministic maternal effects can always invade an ancestral state lacking a maternal effect even if the amount of environmental information available is low. The long-term outcome may involve offspring trait value randomization but only if trait values first evolve to cause extreme differences in environment-specific fitness. Overall, deterministic maternal effects are more likely to evolve by natural selection than randomizing maternal effects.

Reproductive assurance drives transitions to self-fertilization in experimental Caenorhabditis elegans.

BACKGROUND: Evolutionary transitions from outcrossing between individuals to selfing are partly responsible for the great diversity of animal and plant reproduction systems. The hypothesis of 'reproductive assurance' suggests that transitions to selfing occur because selfers that are able to reproduce on their own ensure the persistence of populations in environments where mates or pollination agents are unavailable. Here we test this hypothesis by performing experimental evolution in Caenorhabditis elegans. RESULTS: We show that self-compatible hermaphrodites provide reproductive assurance to a male-female population facing a novel environment where outcrossing is limiting. Invasions of hermaphrodites in male-female populations, and subsequent experimental evolution in the novel environment, led to successful transitions to selfing and adaptation. Adaptation was not due to the loss of males during transitions, as shown by evolution experiments in exclusively hermaphroditic populations and in male-hermaphrodite populations. Instead, adaptation was due to the displacement of females by hermaphrodites. Genotyping of single-nucleotide polymorphisms further indicated that the observed evolution of selfing rates was not due to selection of standing genetic diversity. Finally, numerical modelling and evolution experiments in male-female populations demonstrate that the improvement of male fitness components may diminish the opportunity for reproductive assurance. CONCLUSIONS: Our findings support the hypothesis that reproductive assurance can drive the transition from outcrossing to selfing, and further suggest that the success of transitions to selfing hinges on adaptation of obligate outcrossing populations to the environment where outcrossing was once a limiting factor.

The role of hermaphrodites in the experimental evolution of increased outcrossing rates in Caenorhabditis elegans.

BACKGROUND: Why most organisms reproduce via outcrossing rather than selfing is a central question in evolutionary biology. It has long ago been suggested that outcrossing is favoured when it facilitates adaptation to novel environments. We have previously shown that the experimental evolution of increased outcrossing rates in populations of the male-hermaphrodite nematode Caenorhabditis elegans were correlated with the experimental evolution of increased male fitness. However, it is unknown whether outcrossing led to adaptation, and if so, which fitness components can explain the observed increase in outcrossing rates. RESULTS: Using experimental evolution in six populations with initially low standing levels of genetic diversity, we show with head-to-head competition assays that population-wide fitness improved during 100 generations. Since outcrossing rates increased during the same period, this result demonstrates that outcrossing is adaptive. We also show that there was little evolution of hermaphrodite fitness under conditions of selfing or under conditions of outcrossing with unrelated tester males. We nonetheless find a positive genetic correlation between hermaphrodite self-fitness and population-wide fitness, and a negative genetic correlation between hermaphrodite mating success and population-wide fitness. These results suggest that the several hermaphrodite traits measured are fitness components. Tradeoffs expressed in hermaphrodites, particularly noticed between self-fitness and mating success, may in turn explain their lack of change during experimental evolution. CONCLUSIONS: Our findings indicate that outcrossing facilitates adaptation to novel environments. They further indicate that the experimental evolution of increased outcrossing rates depended little on hermaphrodites because of fitness tradeoffs between selfing and outcrossing. Instead, the evolution of increased outcrossing rates appears to have resulted from unhindered selection on males.

Hermaphrodite life history and the maintenance of partial selfing in experimental populations of Caenorhabditis elegans.

BACKGROUND: Classic population genetics theory predicts that mixed reproductive systems, where self reproduction (selfing) and outcrossing co-exist, should not be as common as they are in nature. One means of reconciling theory with observations is to recognize that sexual conflict between males and hermaphrodites and/or constraints in the allocation of resources towards sex functions in hermaphrodites can balance the fitness components of selfing and outcrossing. RESULTS: Using experimental evolution in Caenorhabditis elegans, we test whether the adaptive maintenance of partial selfing is due to sexual conflict and/or to the evolution of sex allocation towards male function in hermaphrodites. For this, we characterized the reproductive schedule and longevity patterns in hermaphrodites under selfing and under outcrossing with naïve males that did not have the opportunity to evolve with them. A shift in reproductive schedule towards earlier reproduction would be indicative of adaptation in our imposed life-cycle, while longevity is expected to evolve as a response to the harm that males impinge on hermaphrodites upon mating. To determine adaptation in the absence of constraints in sex allocation, we also characterized the life history of females that reproduced during experimental evolution through obligate mating with males. As expected with adaptation, we find that after 100 generations of experimental evolution, selfing hermaphrodites and females showed improved reproduction at earlier ages. We did not observe similar reproductive shifts in outcrossed hermaphrodites. We further find increased longevity in outcrossed females after evolution but not in outcrossed hermaphrodites, a result that indicates that sexual conflicts were likely more prevalent under male-female evolution than under male-hermaphrodite evolution. CONCLUSIONS: Taken together, our findings suggest that the adaptive maintenance of partial selfing during C. elegans experimental evolution resulted from the evolution of sex allocation towards male function in hermaphrodites.

The population genomics of repeated evolution in the blind cavefish Astyanax mexicanus.

Distinct populations of Astyanax mexicanus cavefish offer striking examples of repeatable convergence or parallelism in their independent evolutions from surface to cave phenotypes. However, the extent to which the repeatability of evolution occurred at the genetic level remains poorly understood. To address this, we first characterized the genetic diversity of 518 single-nucleotide polymorphisms (SNPs), obtained through RAD tag sequencing and distributed throughout the genome, in seven cave and three groups of surface populations. The cave populations represented two distinct lineages (old and new). Thirty-one SNPs were significantly differentiated between surface and old cave populations, two SNPs were differentiated between surface and new cave populations, and 44 SNPs were significantly differentiated in both old and new cave populations. In addition, we determined whether these SNPs map to the same locations of previously described quantitative trait loci (QTL) between surface and cave populations. A total of 25 differentiated SNPs co-map with several QTL, such as one containing a fibroblast growth factor gene (Fgf8) involved in eye development and lens size. Further, the identity of many SNPs that co-mapped with QTL was the same in independently derived cave populations. These conclusions were further confirmed by haplotype analyses of SNPs within QTL regions. Our findings indicate that the repeatability of evolution at the genetic level is substantial, suggesting that ancestral standing genetic variation significantly contributed to the population genetic variability used in adaptation to the cave environment.

rec-1 loss of function increases recombination in the central gene clusters at the expense of autosomal pairing centers.

Meiotic control of crossover (CO) number and position is critical for homologous chromosome segregation and organismal fertility, recombination of parental genotypes, and the generation of novel genetic combinations. We here characterize the recombination rate landscape of a rec-1 loss of function modifier of CO position in Caenorhabditis elegans, one of the first ever modifiers discovered. By averaging CO position across hermaphrodite and male meioses and by genotyping 203 single-nucleotide variants covering about 95% of the genome, we find that the characteristic chromosomal arm-center recombination rate domain structure is lost in the loss of function rec-1 mutant. The rec-1 loss of function mutant smooths the recombination rate landscape but is insufficient to eliminate the nonuniform position of CO. Lower recombination rates in the rec-1 mutant are particularly found in the autosomal arm domains containing the pairing centers. We further find that the rec-1 mutant is of little consequence for organismal fertility and egg viability and thus for rates of autosomal nondisjunction. It nonetheless increases X chromosome nondisjunction rates and thus male appearance. Our findings question the maintenance of recombination rate heritability and genetic diversity among C. elegans natural populations, and they further suggest that manipulating genetic modifiers of CO position will help find quantitative trait loci located in low-recombining genomic regions normally refractory to discovery.

Steep clines within a highly permeable genome across a hybrid zone between two subspecies of the European rabbit.

Maintenance of genetic distinction in the face of gene flow is an important aspect of the speciation process. Here, we provide a detailed spatial and genetic characterization of a hybrid zone between two subspecies of the European rabbit. We examined patterns of allele frequency change for 22 markers located on the autosomes, X-chromosome, Y-chromosome and mtDNA in 1078 individuals sampled across the hybrid zone. While some loci revealed extremely wide clines (w ≥ 300 km) relative to an estimated dispersal of 1.95-4.22 km/generation, others showed abrupt transitions (w ≈ 10 km), indicating localized genomic regions of strong selection against introgression. The subset of loci showing steep clines had largely coincident centers and stepped changes in allele frequency that did not co-localize with any physical barrier or ecotone, suggesting that the rabbit hybrid zone is a tension zone. The steepest clines were for X- and Y-chromosome markers. Our results are consistent with previous inference based on DNA sequence variation of individuals sampled in allopatry in suggesting that a large proportion of each genome has escaped the overall barrier to gene flow in the middle of the hybrid zone. These results imply an old history of hybridization and high effective gene flow and anticipate that isolation factors should often localize to small genomic regions.

Selection and the direction of phenotypic evolution.

Predicting adaptive phenotypic evolution depends on invariable selection gradients and on the stability of the genetic covariances between the component traits of the multivariate phenotype. We describe the evolution of six traits of locomotion behavior and body size in the nematode Caenorhabditis elegans for 50 generations of adaptation to a novel environment. We show that the direction of adaptive multivariate phenotypic evolution can be predicted from the ancestral selection differentials, particularly when the traits were measured in the new environment. Interestingly, the evolution of individual traits does not always occur in the direction of selection, nor are trait responses to selection always homogeneous among replicate populations. These observations are explained because the phenotypic dimension with most of the ancestral standing genetic variation only partially aligns with the phenotypic dimension under directional selection. These findings validate selection theory and suggest that the direction of multivariate adaptive phenotypic evolution is predictable for tens of generations.

Variation in mutational (co)variances.

Because of pleiotropy, mutations affect the expression and inheritance of multiple traits and, together with selection, are expected to shape standing genetic covariances between traits and eventual phenotypic divergence between populations. It is therefore important to find if the M matrix, describing mutational variances of each trait and covariances between traits, varies between genotypes. We here estimate the M matrix for six locomotion behavior traits in lines of two genotypes of the nematode Caenorhabditis elegans that accumulated mutations in a nearly neutral manner for 250 generations. We find significant mutational variance along at least one phenotypic dimension of the M matrices, but neither their size nor their orientation had detectable differences between genotypes. The number of generations of mutation accumulation, or the number of MA lines measured, was likely insufficient to sample enough mutations and detect potentially small differences between the two M matrices. We then tested if the M matrices were similar to one G matrix describing the standing genetic (co)variances of a population derived by the hybridization of several genotypes, including the two measured for M, and domesticated to a lab-defined environment for 140 generations. We found that the M and G were different because the genetic covariances caused by mutational pleiotropy in the two genotypes are smaller than those caused by linkage disequilibrium in the lab population. We further show that M matrices differed in their alignment with the lab population G matrix. If generalized to other founder genotypes of the lab population, these observations indicate that selection does not shape the evolution of the M matrix for locomotion behavior in the short-term of a few tens to hundreds of generations and suggests that the hybridization of C. elegans genotypes allows selection on new phenotypic dimensions of locomotion behavior.

Towards evolutionary predictions: Current promises and challenges.

Evolution has traditionally been a historical and descriptive science, and predicting future evolutionary processes has long been considered impossible. However, evolutionary predictions are increasingly being developed and used in medicine, agriculture, biotechnology and conservation biology. Evolutionary predictions may be used for different purposes, such as to prepare for the future, to try and change the course of evolution or to determine how well we understand evolutionary processes. Similarly, the exact aspect of the evolved population that we want to predict may also differ. For example, we could try to predict which genotype will dominate, the fitness of the population or the extinction probability of a population. In addition, there are many uses of evolutionary predictions that may not always be recognized as such. The main goal of this review is to increase awareness of methods and data in different research fields by showing the breadth of situations in which evolutionary predictions are made. We describe how diverse evolutionary predictions share a common structure described by the predictive scope, time scale and precision. Then, by using examples ranging from SARS-CoV2 and influenza to CRISPR-based gene drives and sustainable product formation in biotechnology, we discuss the methods for predicting evolution, the factors that affect predictability and how predictions can be used to prevent evolution in undesirable directions or to promote beneficial evolution (i.e. evolutionary control). We hope that this review will stimulate collaboration between fields by establishing a common language for evolutionary predictions.

Gene-level quantitative trait mapping in Caenorhabditis elegans.

The Caenorhabditis elegans multiparental experimental evolution (CeMEE) panel is a collection of genome-sequenced, cryopreserved recombinant inbred lines useful for mapping the evolution and genetic basis of quantitative traits. We have expanded the resource with new lines and new populations, and here report the genotype and haplotype composition of CeMEE version 2, including a large set of putative de novo mutations, and updated additive and epistatic mapping simulations. Additive quantitative trait loci explaining 4% of trait variance are detected with >80% power, and the median detection interval approaches single-gene resolution on the highly recombinant chromosome arms. Although CeMEE populations are derived from a long-term evolution experiment, genetic structure is dominated by variation present in the ancestral population.

Testing the adaptive value of sporulation in budding yeast using experimental evolution.

Saccharomyces yeast grow through mitotic cell division, converting resources into biomass. When cells experience starvation, sporulation is initiated and meiosis produces haploid cells inside a protective ascus. The protected spore state does not acquire resources and is partially protected from desiccation, heat, and caustic chemicals. Because cells cannot both be protected and acquire resources simultaneously, committing to sporulation represents a trade-off between current and future reproduction. Recent work has suggested that passaging through insect guts selects for spore formation, as surviving insect ingestion represents a major way that yeasts are vectored to new food sources. We subjected replicate populations from five yeast strains to passaging through insects, and evolved control populations by pipette passaging. We assayed populations for their propensity to sporulate after resource depletion. We found that ancestral domesticated strains produced fewer spores, and all strains evolved increased spore production in response to passaging through flies, but domesticated strains responded less. Exposure to flies led to a more rapid shift to sporulation that was more extreme in wild-derived strains. Our results indicate that insect passaging selects for spore production and suggest that domestication led to genetic canalization of the response to cues in the environment and initiation of sporulation.

A single-nucleotide change underlies the genetic assimilation of a plastic trait.

Genetic assimilation-the evolutionary process by which an environmentally induced phenotype is made constitutive-represents a fundamental concept in evolutionary biology. Thought to reflect adaptive phenotypic plasticity, matricidal hatching in nematodes is triggered by maternal nutrient deprivation to allow for protection or resource provisioning of offspring. Here, we report natural Caenorhabditis elegans populations harboring genetic variants expressing a derived state of near-constitutive matricidal hatching. These variants exhibit a single amino acid change (V530L) in KCNL-1, a small-conductance calcium-activated potassium channel subunit. This gain-of-function mutation causes matricidal hatching by strongly reducing the sensitivity to environmental stimuli triggering egg-laying. We show that reestablishing the canonical KCNL-1 protein in matricidal isolates is sufficient to restore canonical egg-laying. While highly deleterious in constant food environments, KCNL-1 V530L is maintained under fluctuating resource availability. A single point mutation can therefore underlie the genetic assimilation-by either genetic drift or selection-of an ancestrally plastic trait.

Partial Selfing Can Reduce Genetic Loads While Maintaining Diversity During Experimental Evolution.

Partial selfing, whereby self- and cross- fertilization occur in populations at intermediate frequencies, is generally thought to be evolutionarily unstable. Yet, it is found in natural populations. This could be explained if populations with partial selfing are able to reduce genetic loads and the possibility for inbreeding depression while keeping genetic diversity that may be important for future adaptation. To address this hypothesis, we compare the experimental evolution of Caenorhabditis elegans populations under partial selfing, exclusive selfing or predominant outcrossing, while they adapt to osmotically challenging conditions. We find that the ancestral genetic load, as measured by the risk of extinction upon inbreeding by selfing, is maintained as long as outcrossing is the main reproductive mode, but becomes reduced otherwise. Analysis of genome-wide single-nucleotide polymorphisms (SNPs) during experimental evolution and among the inbred lines that survived enforced inbreeding indicates that populations with predominant outcrossing or partial selfing maintained more genetic diversity than expected with neutrality or purifying selection. We discuss the conditions under which this could be explained by the presence of recessive deleterious alleles and/or overdominant loci. Taken together, our observations suggest that populations evolving under partial selfing can gain some of the benefits of eliminating unlinked deleterious recessive alleles and also the benefits of maintaining genetic diversity at partially dominant or overdominant loci that become associated due to variance of inbreeding levels.

Selection against males in Caenorhabditis elegans under two mutational treatments.

Within populations with mixed mating systems, selfing is expected to be favoured over outcrossing unless a countervailing process such as severe inbreeding depression is present. In this study, we consider the relationship between the expression of deleterious alleles and the maintenance of outcrossing in the nematode species, Caenorhabditis elegans. This species is characterized by an androdioecious breeding system composed of males at low frequency and self-fertilizing hermaphrodites that can only outcross via males. Here, we find that experimentally increasing the mutational load in four different isogenic wild isolates using 10 generations of Ethylmethane sulphonate (EMS) and UV irradiation mutagenesis significantly diminishes the cost of males. Males are maintained at higher frequencies in mutagenized versus non-mutagenized populations. Nevertheless, males still tend to be driven to low frequencies within isolates that are known to be prone to lose males. Further, we determine the viability effects of a single round of mutagen exposure and find that, for EMS, outcrossing overcomes the almost completely recessive and nearly lethal effects generated. We briefly interpret our results in light of current evolutionary theory of outcrossing rates.