Nemo: an evolutionary and population genetics programming framework

Nemo is an individual-based, genetically explicit and stochastic population computer program for the simulation of population genetics and life-history trait evolution in a metapopulation context. It comes as both a C++ programming framework and an executable program file. Its object-oriented programming design gives it the flexibility and extensibility needed to implement a large variety of forward-time evolutionary models. It provides developers with abstract models allowing them to implement their own life-history traits and life-cycle events. Nemo offers a large panel of population models, from the Island model to lattice models with demographic or environmental stochasticity and a variety of already implemented traits (deleterious mutations, neutral markers and more), life-cycle events (mating, dispersal, aging, selection, etc.) and output operators for saving data and statistics. It runs on all major computer platforms including parallel computing environments. AVAILABILITY: The source code, binaries and documentation are available under the GNU General Public License at http://nemo2.sourceforge.net.     

The Interaction between Selection,Demography and Selfing and How It Affects Population Viability

Population extinction due to the accumulation of deleterious mutations has only been considered to occur at small population sizes, large sexual populations being expected to efficiently purge these mutations. However, little is known about how the mutation load generated by segregating mutations affects population size and, eventually, population extinction. We propose a simple analytical model that takes into account both the demographic and genetic evolution of populations, linking population size, density dependence, the mutation load, and self-fertilisation. Analytical predictions were found to be relatively good predictors of population size and probability of population viability when verified using an explicit individual based stochastic model. We show that initially large populations do not always reach mutation-selection balance and can go extinct due to the accumulation of segregating deleterious mutations. Population survival depends not only on the relative fitness and demographic stochasticity, but also on the interaction between the two. When deleterious mutations are recessive, self-fertilisation affects viability non-monotonically and genomic cold-spots could favour the viability of outcrossing populations.     

Surfing downhill: when should population range expansion be characterized by reductions in fitness?

Deleterious mutations are found in all populations. Their existence at low frequencies is easily understood, but explaining how they reach high frequencies has long been a challenging problem for population geneticists and evolutionary biologists. Some cases of apparently deleterious alleles are explained by pleiotropy or environmental context dependence, but for universally deleterious alleles, two mechanisms are generally invoked to explain how they can reach high frequencies: (i) genetic drift in small populations and (ii) ‘hitchhiking’ (sensu Maynard Smith J, Haigh J, Genetical Research, 1974, 23, 23–35) involving tight linkage to beneficial mutations. However, these oft‐cited explanations do not immediately resolve the problem because many real populations of interest have population sizes and recombination rates that are large enough to render it nearly impossible for all but the most weakly deleterious (i.e. nearly neutral) mutations to establish and persist. Furthermore, both mechanisms are usually silent about patterns of intraspecific variation in mutation load. In this issue, Peischl S, Dupanloup I, Kirkpatrick M, Excoffier L (Molecular Ecology, 2013) develop and explore a mechanism that puts drift and hitchhiking of deleterious mutations into a specific spatial and demographic context: range expansions. Importantly, their findings provide a plausible explanation for puzzling empirical patterns, such as the paradoxical observation that genotypes at the leading edge of a range expansion are sometimes less fit than those in the ancestral range (when fitness is assessed in a common environment).     

The highs and lows of dispersal: how connectivity and initial population size jointly shape establishment dynamics in discrete landscapes

Identifying the main factors driving introduced populations to establishment is a major challenge of invasion biology. Due to their small initial size, introduced populations are most vulnerable to extinction because of demographic stochasticity or Allee effects. While an increase in initial population size is known to increase establishment success, much remains to be understood regarding its interplay with connectivity in spatially structured environments. In order to better understand how demographic mechanisms interact at such spatial scale, we developed a stochastic model of population dynamics in discrete space to investigate the effect of connectivity and initial population size on establishment. The predictions derived from the model were then tested using experimental introductions of an insect parasitoid (Trichogramma chilonis) in spatially structured laboratory microcosms. Both theoretical and experimental results demonstrated that the connectivity of the introduction site had 1) a deleterious effect in the first generation when the introduced population was small and 2) a beneficial impact brought about by metapopulation effects in the subsequent generations. Interestingly, populations displayed a weakly pushed invasion pattern promoting early establishment, which was mainly underpinned by dispersal stochasticity and the discrete nature of the landscape. These results shed light on the critical influence of landscape connectivity on establishment dynamics.     

Deleterious mutations can surf to high densities on the wave front of an expanding population

There is an increasing recognition that evolutionary processes play a key role in determining the dynamics of range expansion. Recent work demonstrates that neutral mutations arising near the edge of a range expansion sometimes surf on the expanding front leading them rather than that leads to reach much greater spatial distribution and frequency than expected in stationary populations. Here, we extend this work and examine the surfing behavior of nonneutral mutations. Using an individual-based coupled-map lattice model, we confirm that, regardless of its fitness effects, the probability of survival of a new mutation depends strongly upon where it arises in relation to the expanding wave front. We demonstrate that the surfing effect can lead to deleterious mutations reaching high densities at an expanding front, even when they have substantial negative effects on fitness. Additionally, we highlight that this surfing phenomenon can occur for mutations that impact reproductive rate (i.e., number of offspring produced) as well as mutations that modify juvenile competitive ability. We suggest that these effects are likely to have important consequences for rates of spread and the evolution of spatially expanding populations.     

A Ruby in the Rubbish: Beneficial Mutations, Deleterious Mutations and the Evolution of Sex

This study presents a mathematical model in which a single beneficial mutation arises in a very large population that is subject to frequent deleterious mutations. The results suggest that, if the population is sexual, then the deleterious mutations will have little effect on the ultimate fate of the beneficial mutation. However, if most offspring are produced asexually, then the probability that the beneficial mutation will be lost from the population may be greatly enhanced by the deleterious mutations. Thus, sexual populations may adapt much more quickly than populations where most reproduction is asexual. Some of the results were produced using computer simulation methods, and a technique was developed that allows treatment of arbitrarily large numbers of individuals in a reasonable amount of computer time. This technique may be of prove useful for the analysis of a wide variety of models, though there are some constraints on its applicability. For example, the technique requires that reproduction can be described by Poisson processes.     

Joint inference of the distribution of fitness effects of deleterious mutations and population demography based on nucleotide polymorphism frequencies

The distribution of fitness effects of new mutations (DFE) is important for addressing several questions in genetics, including the nature of quantitative variation and the evolutionary fate of small populations. Properties of the DFE can be inferred by comparing the distributions of the frequencies of segregating nucleotide polymorphisms at selected and neutral sites in a population sample, but demographic changes alter the spectrum of allele frequencies at both neutral and selected sites, so can bias estimates of the DFE if not accounted for. We have developed a maximum-likelihood approach, based on the expected allele-frequency distribution generated by transition matrix methods, to estimate parameters of the DFE while simultaneously estimating parameters of a demographic model that allows a population size change at some time in the past. We tested the method using simulations and found that it accurately recovers simulated parameter values, even if the simulated demography differs substantially from that assumed in our analysis. We use our method to estimate parameters of the DFE for amino acid-changing mutations in humans and Drosophila melanogaster. For a model of unconditionally deleterious mutations, with effects sampled from a gamma distribution, the mean estimate for the distribution shape parameter is approximately 0.2 for human populations, which implies that the DFE is strongly leptokurtic. For Drosophila populations, we estimate that the shape parameter is approximately 0.35. Differences in the shape of the distribution and the mean selection coefficient between humans and Drosophila result in significantly more strongly deleterious mutations in Drosophila than in humans, and, conversely, nearly neutral mutations are significantly less frequent.     

Bottlenecks in large populations: the effect of immigration on population viability

We model a large population that is subject to successive short bottlenecks, in order to investigate the impact of different extents of immigration on the change in genetic load and on viability. A first simple genetic model uncovers the opposite effects of immigration on fitness according to the type of deleterious mutations considered: immigration increases fitness if the genetic load is comprised of mildly deleterious mutations, whereas it decreases fitness if it is comprised of lethals. When considering both types of mutations and adding explicit stochastic demographic considerations, in which bottlenecks are engendered by random catastrophes, the global impact of immigration on viability is dependent upon a balance between its opposite effects on the two components of the genetic load and on demographic stochasticity. In this context, immigration tends to increase the probability of extinction if occurring preferentially when population density is high, while it decreases extinction if occurring preferentially towards low-density populations.     

Mutation accumulation in a selfing population: consequences of different mutation rates between selfers and outcrossers

Currently existing theories predict that because deleterious mutations accumulate at a higher rate, selfing populations suffer from more intense genetic degradation relative to outcrossing populations. This prediction may not always be true when we consider a potential difference in deleterious mutation rate between selfers and outcrossers. By analyzing the evolutionary stability of selfing and outcrossing in an infinite population, we found that the genome-wide deleterious mutation rate would be lower in selfing than in outcrossing organisms. When this difference in mutation rate was included in simulations, we found that in a small population, mutations accumulated more slowly under selfing rather than outcrossing. This result suggests that under frequent and intense bottlenecks, a selfing population may have a lower risk of genetic extinction than an outcrossing population.     

Introduction of Trojan sex chromosomes to boost population growth

Conservation programs that deal with small or declining populations often aim at a rapid increase of population size to above-critical levels in order to avoid the negative effects of demographic stochasticity and genetic problems like inbreeding depression, fixation of deleterious alleles, or a general loss of genetic variability and hence of evolutionary potential. In some situations, population growth is determined by the number of females available for reproduction, and manipulation of family sex ratios towards more daughters has beneficial effects. If sex determination is predominantly genetic but environmentally reversible, as is the case in many amphibia, reptiles, and fish, Trojan sex chromosomes could be introduced into populations in order to change sex ratios towards more females. We analyse the possible consequences for the introduction of XX-males (XX individuals that have been changed to phenotypic males in a XY/XX sex determination system) and ZW males, WW males, or WW females (in a ZZ/ZW sex determination system). We find that the introduction of WW individuals can be most effective for an increase of population growth, especially if the induced sex change has little or no effect on viability.     

Neutral processes forming large clones during colonization of new areas

In species reproducing both sexually and asexually clones are often more common in recently established populations. Earlier studies have suggested that this pattern arises due to natural selection favouring generally or locally successful genotypes in new environments. Alternatively, as we show here, this pattern may result from neutral processes during species’ range expansions. We model a dioecious species expanding into a new area in which all individuals are capable of both sexual and asexual reproduction, and all individuals have equal survival rates and dispersal distances. Even under conditions that favour sexual recruitment in the long run, colonization starts with an asexual wave. After colonization is completed, a sexual wave erodes clonal dominance. If individuals reproduce more than one season, and with only local dispersal, a few large clones typically dominate for thousands of reproductive seasons. Adding occasional long‐distance dispersal, more dominant clones emerge, but they persist for a shorter period of time. The general mechanism involved is simple: edge effects at the expansion front favour asexual (uniparental) recruitment where potential mates are rare. Specifically, our model shows that neutral processes (with respect to genotype fitness) during the population expansion, such as random dispersal and demographic stochasticity, produce genotype patterns that differ from the patterns arising in a selection model. The comparison with empirical data from a post‐glacially established seaweed species (Fucus radicans) shows that in this case, a neutral mechanism is strongly supported.     

Dynamic mutation-selection balance as an evolutionary attractor

The vast majority of mutations are deleterious and are eliminated by purifying selection. Yet in finite asexual populations, purifying selection cannot completely prevent the accumulation of deleterious mutations due to Muller's ratchet: once lost by stochastic drift, the most-fit class of genotypes is lost forever. If deleterious mutations are weakly selected, Muller's ratchet can lead to a rapid degradation of population fitness. Evidently, the long-term stability of an asexual population requires an influx of beneficial mutations that continuously compensate for the accumulation of the weakly deleterious ones. Hence any stable evolutionary state of a population in a static environment must involve a dynamic mutation-selection balance, where accumulation of deleterious mutations is on average offset by the influx of beneficial mutations. We argue that such a state can exist for any population size N and mutation rate U and calculate the fraction of beneficial mutations, ε, that maintains the balanced state. We find that a surprisingly low ε suffices to achieve stability, even in small populations in the face of high mutation rates and weak selection, maintaining a well-adapted population in spite of Muller's ratchet. This may explain the maintenance of mitochondria and other asexual genomes.     

Complexity and demographic stability in population models

This article is concerned with relating the stability of a population, as defined by the rate of decay of fluctuations induced by demographic stochasticity, with its heterogeneity in age-specific birth and death rates. We invoke the theory of large deviations to establish a fluctuation theorem: The demographic stability of a population is positively correlated with evolutionary entropy, a measure of the variability in the age of reproducing individuals in the population. This theorem is exploited to predict certain correlations between ecological constraints and evolutionary trends in demographic stability, namely, (i) bounded growth constraints--a uni-directional increase in stability, (ii) unbounded growth constraints (large population size)--a uni-directional decrease in stability, (iii) unbounded growth constraints (small population size)--random, non-directional change in stability. These principles relating ecological constraints with trends in demographic stability are shown to be far reaching generalizations of the tenets derived from classical studies of stability in an evolutionary context. These results thus provide a new conceptual framework for explaining patterns of variation in population numbers observed in natural populations.     

On the constancy of the evolutionary rate of cistrons

Summary The variations of evolutionary rates in hemoglobins and cytochrome c among various lines of vertebrates are analysed by estimating the variance. The observed variances appear to be larger than expected purely by chance.If the amino acid substitutions in evolution are the result of random fixation of selectively neutral or nearly neutral mutations, the evolutionary rate of cistrons can be represented by the integral of the product of mutation rate and fixation probability in terms of selective values around the neutral point. This integral is called the effective neutral mutation rate.The influence of effective population number and generation time on the effective neutral mutation rate is discussed. It is concluded that the uniformity of the rate of amino acid substitutions over diverse lines is compatible with random fixation of neutral or very slightly deleterious mutations which have some chance of being selected against during the course of substitution. On the other hand, definitely advantageous mutations will introduce significant variation in the substitution rate among lines. Approximately 10% of the amino acid substitutions of average cistrons might be adaptive and create slight but significant variations in evolutionary rate among vertebrate lines, although the uniformity of evolutionary rate is still valid as a first approximation.Contribution No. 813 from the National Institute of Genetics, Mishima, Shizuokaken 411 Japan. Aided in part by a grant-in-aid from the Ministry of Education, Japan.     

Adaptive and maladaptive genetic diversity in small populations: Insights from the Brook Charr (Salvelinus fontinalis) case study

Investigating the relative importance of neutral versus selective processes governing the accumulation of genetic variants is a key goal in both evolutionary and conservation biology. This is particularly true in the context of small populations, where genetic drift can counteract the effect of selection. Using Brook Charr (Salvelinus fontinalis) from Québec, Canada, as a case study, we investigated the importance of demographic versus selective processes governing the accumulation of both adaptive and maladaptive mutations in closed versus open and connected populations to assess gene flow effect. This was achieved by using 14,779 high‐quality filtered SNPs genotyped among 1,416 fish representing 50 populations from three life history types: lacustrine (closed populations), riverine and anadromous (connected populations). Using the PROVEAN algorithm, we observed a considerable accumulation of putative deleterious mutations across populations. The absence of correlation between the occurrence of putatively beneficial or deleterious mutations and local recombination rate supports the hypothesis that genetic drift might be the main driver of the accumulation of such variants. However, despite a lower genetic diversity observed in lacustrine than in riverine or anadromous populations, lacustrine populations do not exhibit more deleterious mutations than the two other history types, suggesting that the negative effect of genetic drift in lacustrine populations may be mitigated by that of relaxed purifying selection. Moreover, we also identified genomic regions associated with anadromy, as well as an overrepresentation of transposable elements associated with variation in environmental variables, thus supporting the importance of transposable elements in adaptation.     

THE ADAPTATION RATE OF ASEXUALS: DELETERIOUS MUTATIONS,CLONAL INTERFERENCE AND POPULATION BOTTLENECKS

The rate at which a population adapts to its environment is a cornerstone of evolutionary theory, and recent experimental advances in microbial populations have renewed interest in predicting and testing this rate. Efforts to understand the adaptation rate theoretically are complicated by high mutation rates, to both beneficial and deleterious mutations, and by the fact that beneficial mutations compete with each other in asexual populations (clonal interference). Testable predictions must also include the effects of population bottlenecks, repeated reductions in population size imposed by the experimental protocol. In this contribution, we integrate previous work that addresses each of these issues, developing an overall prediction for the adaptation rate that includes: beneficial mutations with probabilistically distributed effects, deleterious mutations of arbitrary effect, population bottlenecks, and clonal interference.     

Revisiting the notion of deleterious sweeps

It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites—both in the presence and absence of interference amongst deleterious mutations—and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of F_ST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.     

Mutation surfing and the evolution of dispersal during range expansions

A growing body of empirical evidence demonstrates that at an expanding front, there can be strong selection for greater dispersal propensity, whereas recent theory indicates that mutations occurring towards the front of a spatially expanding population can sometimes ‘surf’ to high frequency and spatial extent. Here, we consider the potential interplay between these two processes: what role may mutation surfing play in determining the course of dispersal evolution and how might dispersal evolution itself influence mutation surfing? Using an individual‐based coupled‐map lattice model, we first run simulations to determine the fate of dispersal mutants that occur at an expanding front. Our results highlight that mutants that have a slightly higher dispersal propensity than the wild type always have a higher survival probability than those mutants with a dispersal propensity lower than, or very similar to, the wild type. However, it is not always the case that mutants with very high dispersal propensity have the greatest survival probability. When dispersal mortality is high, mutants of intermediate dispersal survive most often. Interestingly, the rate of dispersal that ultimately evolves at an expanding front is often substantially higher than that which confers a novel mutant with the greatest probability of survival. Second, we run a model in which we allow dispersal to evolve over the course of a range expansion and ask how the fate of a neutral or nonneutral mutant depends upon when and where during the expansion it arises. These simulations highlight that the success of a neutral mutant depends upon the dispersal genotypes that it is associated with. An important consequence of this is that novel mutants that arise at the front of an expansion, and survive, typically end up being associated with more dispersive genotypes than the wild type. These results offer some new insights into causes and the consequences of dispersal evolution during range expansions, and the methodology we have employed can be readily extended to explore the evolutionary dynamics of other life history characteristics.     

Evidences of Moran effect in the population synchrony: a demonstration in experimental microcosm

Three main causes to population synchrony are proposed: exogenous factors, dispersal and inter-specific interactions. This paper had as main goal to test the influence of the exogenous factors in the synchrony in spatially isolated (i.e., no dispersal) populations of Sitophilus zeamais (Mots.) (Coleoptera: Curculionidae), in microcosms with different environmental conditions (humidity, temperature and light intensity). Twelve populations of 20 individuals each, were randomly assigned between two treatment conditions: with or without light. Population size and environmental factors (temperature and relative humidity) were weekly assessed for seven months. Temporal trend in populations increase was eliminated adjusting autoregressive models. Population synchrony, detected by means of Pearson's and Spearman's correlation coefficients, was higher within than between treatments, although the populations kept without lamp were more synchronized than populations with lamp. Besides demonstrating the influence of environment on population fluctuations, these results suggest that metabolism and intra-specific interactions are important factors in population dynamic. Organisms exposed to unsuitable environmental conditions may have abnormal metabolic rates, which negatively influences the population grow. Thus, small populations are more likely to suffer from demographic stochasticity, decreasing the probability of the synchrony among populations. On the other hand, in more suitable environments, individuals are expected to have normal metabolic functions, and so, to achieve higher rates of population grow. In this case, the demographic stochasticity has smaller influence, leading populations without lamp to fluctuate synchronously.