Genetic load in subdivided populations: interactions between the migration rate, the size and the number of subpopulations

We assess the relative importance of migration rate, size and number of subpopulations on the genetic load of subdivided populations. Using diffusion approximations, we show that in most cases subdivision has detrimental effects on fitness. Moreover, our results suggest that fitness increases with subpopulation size, so that for the same total population size, genetic load is relatively lower when there are a small number of large subpopulations. Using elasticity analysis, we show that the size of the subpopulations appears to be the parameter that most strongly determines genetic load. interconnecting subpopulations via migration would also be of importance for population fitness when subpopulations are small and gene flow is low. Interestingly, the number of subpopulations has minor influence on genetic load except for the case of both very slightly deleterious mutations and small subpopulations. Elasticities decrease as the magnitude of deleterious effects increases. In other words, population structure does not matter for very deleterious alleles, but strongly affects fitness for slightly deleterious alleles.     

Population size and the nature of genetic load in Gentianella germanica

Abstract Theory predicts a significant relationship between the size of a population and the magnitude and composition of its genetic load, but few natural populations have been investigated. We examined the magnitude of genetic load due to recessive deleterious alleles (GL) both segregating and fixed within Gentianella germanica populations of varying size by selfing and reciprocally crossing plants within and between natural populations according to a partial diallel design and by comparing the performance of the experimental progeny in a common-garden experiment. The results show that GL for total fitness in small populations (fewer than 200 plants) was mainly due to fixed recessive deleterious alleles, whereas GL for total fitness in larger populations (more than 200 plants) appeared to be mainly due to segregating deleterious recessive alleles. The total fitness of selfed plants increased with decreasing population size, indicating some purging of deleterious alleles associated with declining population sizes. The magnitudes of GL due to fixed deleterious alleles in small populations and segregating deleterious alleles in large populations, however, were overall similar, suggesting that purging selection was an insignificant force when compared to genetic drift in determining the magnitude of GL in small natural populations in this species. The results of this study highlight the importance of population size in determining the dynamics of genetic loads of natural populations and are overall in line with a large body of theoretical work indicating that small populations may face higher extinction risks due to the fixation and accumulation of deleterious alleles of small effect.     

Dynamics of genetic rescue in inbred Drosophila melanogaster populations

Genetic rescue has been proposed as a management strategy to improve the fitness of genetically eroded populations by alleviating inbreeding depression. We studied the dynamics of genetic rescue in inbred populations of Drosophila. Using balancer chromosomes, we show that the force of heterosis that accompanies genetic rescue is large and allows even a recessive lethal to increase substantially in frequency in the rescued populations, particularly at stress temperatures. This indicates that deleterious alleles present in the immigrants can increase significantly in frequency in the recipient population when they are in linkage disequilibrium with genes responsible for the heterosis. In a second experiment we rescued eight inbred Drosophila populations with immigrants from two other inbred populations and observe: (i) there is a significant increase in viability both 5 and 10 generations after the rescue event, showing that the increase in fitness is not transient but persists long-term. (ii) The lower the fitness of the recipient population the larger the fitness increase. (iii) The increase in fitness depends significantly on the origin of the rescuers. The immigrants used were fixed for a conditional lethal that was mildly deleterious at 25°C but lethal at 29°C. By comparing fitness at 25°C (the temperature during the rescue experiment) and 29°C, we show that the lethal allele reached significant frequencies in most rescued populations, which upon renewed inbreeding became fixed in part of the inbred lines. In conclusion, in addition to the fitness increase genetic rescue can easily result in a substantial increase in the frequency of mildly deleterious alleles carried by the immigrants. This can endanger the rescued population greatly when it undergoes recurrent inbreeding. However, using a sufficient number of immigrants and to accompany the rescue event with the right demographic measures will overcome this problem. As such, genetic rescue still is a viable option to manage genetically eroded populations.     

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.     

Heterozygosity-fitness correlations among wild populations of European tree frog (Hyla arborea) detect fixation load

Quantifying the impacts of inbreeding and genetic drift on fitness traits in fragmented populations is becoming a major goal in conservation biology. Such impacts occur at different levels and involve different sets of loci. Genetic drift randomly fixes slightly deleterious alleles leading to different fixation load among populations. By contrast, inbreeding depression arises from highly deleterious alleles in segregation within a population and creates variation among individuals. A popular approach is to measure correlations between molecular variation and phenotypic performances. This approach has been mainly used at the individual level to detect inbreeding depression within populations and sometimes at the population level but without consideration about the genetic processes measured. For the first time, we used in this study a molecular approach considering both the interpopulation and intrapopulation level to discriminate the relative importance of inbreeding depression vs. fixation load in isolated and non-fragmented populations of European tree frog (Hyla arborea), complemented with interpopulational crosses. We demonstrated that the positive correlations observed between genetic heterozygosity and larval performances on merged data were mainly caused by co-variations in genetic diversity and fixation load among populations rather than by inbreeding depression and segregating deleterious alleles within populations. Such a method is highly relevant in a conservation perspective because, depending on how populations lose fitness (inbreeding vs. fixation load), specific management actions may be designed to improve the persistence of populations.     

Social selection in human populations: sufficient conditions for protection of deleterious alleles in a subdivided population

Population dynamics of wild type (A1) and the deleterious genes (A2) under social selection have been studied by considering a subdivided population where the i-th subpopulation consists of Ni individuals with relative size ci (= Ni/sigma i Ni, i = 1,2, ..., n). A social selection model is constructed by assuming that the fitness of an individual is determined by its own as well as the parental phenotypes and that the number of migrants (M) from the ith subpopulation is divided equally into other subpopulations including the ith subpopulation itself. It has been shown that the gene frequency change depends on the loss of fitness of an individual due to the trait (gamma), an affected parent in the ith subpopulation (beta i), the probability that the heterozygote develops the trait (h), and the migration rates mi (= M/Ni). For 0 less than h less than or equal to 1, a sufficient condition for protection of the deleterious allele from extinction also depends on all of these parameters. However, when mi much less than 1 for all i, the condition is beta i less than gamma/(1 - gamma) for some i, whereas when mi much greater than h[gamma + beta i(1 - gamma)] for all i it is given by sigma i ci beta i less than -gamma/(1 - gamma). When h = 0, that condition is given by sigma ici beta i less than - gamma/(1 - gamma). Analyses also show that, when the deleterious alleles in a population are rare, the relative fitnesses of A1A1, A1A2, and A2A2 are given approximately by 1, 1-hS, and 1 - S, respectively, where S is the harmonic mean of Si = gamma + beta i(1 - gamma). Thus, under mutation-selection balance, the equilibrium frequency of deleterious alleles in the entire population is given by alpha/hS for 0 less than h less than or equal to 1 and square root alpha/S for h = 0, where alpha is the irreversible mutation rate from A1 to A2 in each generation. Population dynamics of rare deleterious genes under social selection can readily be studied by considering a finite population size.     

The origin and function of self-incompatibility in flowering plants

Summary The evolutionary significance of self-incompatibility (SI) traditionally has been linked to reduced inbreeding through enforced outcrossing. This view is founded on the premise that outcrossing reduces inbreeding. It is important, when considering the evolutionary significance of any genetic system, to try to distinguish those factors related to the evolution of, from those related to the maintenance of, the system in question. Three factors are considered important for the maintenance of SI: (1) phylogenetic constraint in species descended from SI ancestors, (2) reduced inbreeding in populations, and (3) fitness benefits to individuals resulting from the avoidance of selfing. I suggest that the first two factors should be rejected when considering the origin of SI (whether one or more origins are hypothesized) and that the increase in individual fitness resulting from the avoidance of self-fertilization among individuals that are heterozygous for deleterious alleles may be sufficient to account for the origin of SI. Self-fertilization in plants (except in species that predominantly self-fertilize) generally results in a reduction in fitness of some individuals due to the increased expression of deleterious or lethal recessive alleles, regardless of the degree of inbreeding in the population or the frequency of the allele in question. Inbreeding is a consequence of population structure in many outcrossing plant species. Complex (multi-locus and multi-allelic) systems of SI exist that reduce inbreeding. However, it is argued that these are derived either from simpler systems of SI that may have very little or no effect on inbreeding, in which case any effect on level of inbreeding is secondary, or are not true self-incompatibility systems and are part of a regulatory system that serves to balance the level of inbreeding and outbreeding. Multi-locus and multi-allelic systems of SI and heteromorphic systems of SI are discussed in terms of derived versus ancestral characteristics. A reassessment of the role of breeding systems in the development of a population structure promoting inbreeding is suggested, which may have been of crucial importance in the success and diversification of angiosperms.     

Inbreeding rate modifies the dynamics of genetic load in small populations

The negative fitness consequences of close inbreeding are widely recognized, but predicting the long-term effects of inbreeding and genetic drift due to limited population size is not straightforward. As the frequency and homozygosity of recessive deleterious alleles increase, selection can remove (purge) them from a population, reducing the genetic load. At the same time, small population size relaxes selection against mildly harmful mutations, which may lead to accumulation of genetic load. The efficiency of purging and the accumulation of mutations both depend on the rate of inbreeding (i.e., population size) and on the nature of mutations. We studied how increasing levels of inbreeding affect offspring production and extinction in experimental Drosophila littoralis populations replicated in two sizes, N = 10 and N = 40. Offspring production and extinction were measured over 25 generations concurrently with a large control population. In the N = 10 populations, offspring production decreased strongly at low levels of inbreeding, then recovered only to show a consistent subsequent decline, suggesting early expression and purging of recessive highly deleterious alleles and subsequent accumulation of mildly harmful mutations. In the N = 40 populations, offspring production declined only after inbreeding reached higher levels, suggesting that inbreeding and genetic drift pose a smaller threat to population fitness when inbreeding is slow. Our results suggest that highly deleterious alleles can be purged in small populations already at low levels of inbreeding, but that purging does not protect the small populations from eventual genetic deterioration and extinction.     

Fixation of new alleles and the extinction of small populations: drift load, beneficial alleles, and sexual selection

With a small effective population size, random genetic drift is more important than selection in determining the fate of new alleles. Small populations therefore accumulate deleterious mutations. Left unchecked, the effect of these fixed alleles is to reduce the reproductive capacity of a species, eventually to the point of extinction. New beneficial mutations, if fixed by selection, can restore some of this lost fitness. This paper derives the overall change in fitness due to fixation of new deleterious and beneficial alleles, as a function of the distribution of effects of new mutations and the effective population size. There is a critical effective size below which a population will on average decline in fitness, but above which beneficial mutations allow the population to persist. With reasonable estimates of the relevant parameters, this critical effective size is likely to be a few hundred. Furthermore, sexual selection can act to reduce the fixation probability of deleterious new mutations and increase the probability of fixing new beneficial mutations. Sexual selection can therefore reduce the risk of extinction of small populations.     

Inverse Medea as a novel gene drive system for local population replacement: a theoretical analysis

One strategy to control mosquito-borne diseases, such as malaria and dengue fever, on a regional scale is to use gene drive systems to spread disease-refractory genes into wild mosquito populations. The development of a synthetic Medea element that has been shown to drive population replacement in laboratory Drosophila populations has provided encouragement for this strategy but has also been greeted with caution over the concern that transgenes may spread into countries without their consent. Here, we propose a novel gene drive system, inverse Medea, which is strong enough to bring about local population replacement but is unable to establish itself beyond an isolated release site. The system consists of 2 genetic components--a zygotic toxin and maternal antidote--which render heterozygous offspring of wild-type mothers unviable. Through population genetic analysis, we show that inverse Medea will only spread when it represents a majority of the alleles in a population. The element is best located on an autosome and will spread to fixation provided any associated fitness costs are dominant and to very high frequency otherwise. We suggest molecular tools that could be used to build the inverse Medea system and discuss its utility for a confined release of transgenic mosquitoes.     

Reviewing the consequences of genetic purging on the success of rescue programs

Genetic rescue is increasingly considered a promising and underused conservation strategy to reduce inbreeding depression and restore genetic diversity in endangered populations, but the empirical evidence supporting its application is limited to a few generations. Here we discuss on the light of theory the role of inbreeding depression arising from partially recessive deleterious mutations and of genetic purging as main determinants of the medium to long-term success of rescue programs. This role depends on two main predictions: (1) The inbreeding load hidden in populations with a long stable demography increases with the effective population size; and (2) After a population shrinks, purging tends to remove its (partially) recessive deleterious alleles, a process that is slower but more efficient for large populations than for small ones. We also carry out computer simulations to investigate the impact of genetic purging on the medium to long term success of genetic rescue programs. For some scenarios, it is found that hybrid vigor followed by purging will lead to sustained successful rescue. However, there may be specific situations where the recipient population is so small that it cannot purge the inbreeding load introduced by migrants, which would lead to increased fitness inbreeding depression and extinction risk in the medium to long term. In such cases, the risk is expected to be higher if migrants came from a large non-purged population with high inbreeding load, particularly after the accumulation of the stochastic effects ascribed to repeated occasional migration events. Therefore, under the specific deleterious recessive mutation model considered, we conclude that additional caution should be taken in rescue programs. Unless the endangered population harbors some distinctive genetic singularity whose conservation is a main concern, restoration by continuous stable gene flow should be considered, whenever feasible, as it reduces the extinction risk compared to repeated occasional migration and can also allow recolonization events.

     

Inbreeding load, average dominance and the mutation rate for mildly deleterious alleles in Mimulus guttatus

The goal of this study is to provide information on the genetics of inbreeding depression in a primarily outcrossing population of Mimulus guttatus. Previous studies of this population indicate that there is tremendous inbreeding depression for nearly every fitness component and that almost all of this inbreeding depression is due to mildly deleterious alleles rather than recessive lethals or steriles. In this article I assayed the homozygous and heterozygous fitnesses of 184 highly inbred lines extracted from a natural population. Natural selection during the five generations of selfing involved in line formation essentially eliminated major deleterious alleles but was ineffective in purging alleles with minor fitness effects and did not appreciably diminish overall levels of inbreeding depression. Estimates of the average degree of dominance of these mildly deleterious alleles, obtained from the regression of heterozygous fitness on the sum of parental homozygous fitness, indicate that the detrimental alleles are partially recessive for most fitness traits, with h approximately 0.15 for cumulative measures of fitness. The inbreeding load, B, for total fitness is approximately 1.0 in this experiment. These results are consistent with the hypothesis that spontaneous mildly deleterious mutations occur at a rate >0.1 mutation per genome per generation.     

Facultative sexual reproduction under frequency-dependent selection on a single locus

The evolution of a facultative sexual strategy that simultaneously produced sexual and asexual individuals was studied theoretically, under negative frequency-dependence of fitness. The organism was considered to be diploid, characterized by two loci concerning fitness and determining sexual strategy, between which a certain degree of linkage existed. The locus concerning fitness was assumed to involve two alleles, resulting in three genotypes, the relative fitness of an individual being defined by a decreasing function of frequency of its own genotype on this locus in the population. The sexual reproductive strategy was considered to be determined by three alleles; asexual, obligate sexual and facultative sexual. Simulations under various linkages between loci and level of frequency dependence of fitness showed that a facultative sexual strategy was generally able to invade and increase in the population. In particular, when the level of frequency dependence was high to some degree, the facultative strain producing many sexual individuals tended to exclusively occupy the population. Namely, the frequency-dependent selection resulted in a predominance of obligate sexual strategy over asexual strategy, simultaneously causing a subordination of the former to the facultative sexual strategy. This indicated that the evolution of sex should be considered carefully with respect to the possibility of invasion of facultative sex.     

EFFECTIVENESS OF SELECTION IN REDUCING THE GENETIC LOAD IN POPULATIONS OF PEROMYSCUS POLIONOTUS DURING GENERATIONS OF INBREEDING

It has been hypothesized that natural selection reduces the “genetic load” of deleterious alleles from populations that inbreed during bottlenecks, thereby ameliorating impacts of future inbreeding. We tested the efficiency with which natural selection purges deleterious alleles from three subspecies of Peromyscus polionotus during 10 generations of laboratory inbreeding by monitoring pairing success, litter size, viability, and growth in 3604 litters produced from 3058 pairs. In P. p. subgriseus, there was no reduction across generations in inbreeding depression in any of the fitness components. Strongly deleterious recessive alleles may have been removed previously during episodes of local inbreeding in the wild, and the residual genetic load in this population was not further reduced by selection in the lab. In P. p. rhoadsi, four of seven fitness components did show a reduction of the genetic load with continued inbreeding. The average reduction in the genetic load was as expected if inbreeding depression in this population is caused by highly deleterious recessive alleles that are efficiently removed by selection. For P. p. leucocephalus a population that experiences periodic bottlenecks in the wild, the effect of further inbreeding in the laboratory was to exacerbate rather than reduce the genetic load. Recessive deleterious alleles may have been removed from this population during repeated bottlenecks in the wild; the population may be close to a threshold level of heterozygosity below which fitness declines rapidly. Thus, the effects of selection on inbreeding depression varied substantially among populations, perhaps due to different histories of inbreeding and selection.     

Long-term exhaustion of the inbreeding load in Drosophila melanogaster

Inbreeding depression, the decline in fitness of inbred individuals, is a ubiquitous phenomenon of great relevance in evolutionary biology and in the fields of animal and plant breeding and conservation. Inbreeding depression is due to the expression of recessive deleterious alleles that are concealed in heterozygous state in noninbred individuals, the so-called inbreeding load. Genetic purging reduces inbreeding depression by removing these alleles when expressed in homozygosis due to inbreeding. It is generally thought that fast inbreeding (such as that generated by full-sib mating lines) removes only highly deleterious recessive alleles, while slow inbreeding can also remove mildly deleterious ones. However, a question remains regarding which proportion of the inbreeding load can be removed by purging under slow inbreeding in moderately large populations. We report results of two long-term slow inbreeding Drosophila experiments (125–234 generations), each using a large population and a number of derived lines with effective sizes about 1000 and 50, respectively. The inbreeding load was virtually exhausted after more than one hundred generations in large populations and between a few tens and over one hundred generations in the lines. This result is not expected from genetic drift alone, and is in agreement with the theoretical purging predictions. Computer simulations suggest that these results are consistent with a model of relatively few deleterious mutations of large homozygous effects and partially recessive gene action.Subject terms: Quantitative trait, Inbreeding     

Genetic diversity at neutral and adaptive loci determines individual fitness in a long-lived territorial bird

There is compelling evidence about the manifest effects of inbreeding depression on individual fitness and populations' risk of extinction. The majority of studies addressing inbreeding depression on wild populations are generally based on indirect measures of inbreeding using neutral markers. However, the study of functional loci, such as genes of the major histocompatibility complex (MHC), is highly recommended. MHC genes constitute an essential component of the immune system of individuals, which is directly related to individual fitness and survival. In this study, we analyse heterozygosity fitness correlations of neutral and adaptive genetic variation (22 microsatellite loci and two loci of the MHC class II, respectively) with the age of recruitment and breeding success of a decimated and geographically isolated population of a long-lived territorial vulture. Our results indicate a negative correlation between neutral genetic diversity and age of recruitment, suggesting that inbreeding may be delaying reproduction. We also found a positive correlation between functional (MHC) genetic diversity and breeding success, together with a specific positive effect of the most frequent pair of cosegregating MHC alleles in the population. Globally, our findings demonstrate that genetic depauperation in small populations has a negative impact on the individual fitness, thus increasing the populations' extinction risk.     

Neutral mutation as the source of genetic variation in life history traits

The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.     

Mating structure and the cost of deleterious mutation: I. Postponing inbreeding

Mating structure governs the distribution of alleles in populations and thus the extent to which the phenotypes associated with the alleles are manifested. A mating system which initially achieves more genetic identity within individuals than between individuals enhances the probability that a finite population without reproductive excess will become extinct from a recessive lethal or semidominant lethal mutation; however, such a mating system decreases the number of deaths that will ensue if the population size is maintained by replacement of inviable progeny with individuals engendered from the entire mating pool. This is illustrated with Markov chain models for half-sib and double-first-cousin mating in populations of four individuals and by various techniques for analogous large populations. An appropriate choice of mating strategy can mitigate the effect of deleterious mutations, but the determination of which strategy is appropriate depends on how much reproductive excess is available and on the relative costs assigned to individual deaths and the extinction of a population.     

Spatial heterogeneity in the strength of selection against deleterious alleles and the mutation load

According to current estimates of genomic deleterious mutation rates (which are often of the order 0.1-1) the mutation load (defined as a reduction in the average fitness of a population due to the presence of deleterious alleles) may be important in many populations. In this paper, I use multilocus simulations to explore the effect of spatial heterogeneity in the strength of selection against deleterious alleles on the mutation load (for example, it has been suggested that stressful environments may increase the strength of selection). These simulations show contrasted results: in some situations, spatial heterogeneity may greatly reduce the mutation load, due to the fact that migrants coming from demes under stronger selection carry relatively few deleterious alleles, and benefit from a strong advantage within demes under weaker selection (where individuals carry many more deleterious alleles); in other situations, however, deleterious alleles accumulate within demes under stronger selection, due to migration pressure from demes under weaker selection, leading to fitness erosion within those demes. This second situation is more frequent when the productivity of the different demes is proportional to their mean fitness. The effect of spatial heterogeneity is greatly reduced, however, when the response to environmental differences is inconsistent across loci.     

Long-term adaptation of epistatic genetic networks

Gene networks are likely to govern most traits in nature. Mutations at these genes often show functional epistatic interactions that lead to complex genetic architectures and variable fitness effects in different genetic backgrounds. Understanding how epistatic genetic systems evolve in nature remains one of the great challenges in evolutionary biology. Here we combine an analytical framework with individual-based simulations to generate novel predictions about long-term adaptation of epistatic networks. We find that relative to traits governed by independently evolving genes, adaptation with epistatic gene networks is often characterized by longer waiting times to selective sweeps, lower standing genetic variation, and larger fitness effects of adaptive mutations. This may cause epistatic networks to either adapt more slowly or more quickly relative to a nonepistatic system. Interestingly, epistatic networks may adapt faster even when epistatic effects of mutations are on average deleterious. Further, we study the evolution of epistatic properties of adaptive mutations in gene networks. Our results show that adaptive mutations with small fitness effects typically evolve positive synergistic interactions, whereas adaptive mutations with large fitness effects evolve positive synergistic and negative antagonistic interactions at approximately equal frequencies. These results provide testable predictions for adaptation of traits governed by epistatic networks and the evolution of epistasis within networks.