Heredity

Lifespan is a heritable trait with a polygenic architecture. Experimental evolution in combination with re-sequencing has often been used to identify candidate loci for lifespan in Drosophila melanogaster. Previous experiments showed that Drosophila populations experimentally evolved to increase late-life reproduction showed a correlated responses in development time, body size, but also lifespan. Subsequent whole genome sequencing allowed for the identification of candidate loci that correlated to lifespan differentiation. However, it remains difficult to assess whether candidate loci affect lifespan and to what extent such loci pleiotropically underpin multiple traits. Furthermore, recent studies indicate that lifespan effects of loci are often context dependent, but genotype-by-genotype interactions remain understudied. Therefore, here, we report on a study where we genotyped 3210 individuals for 32 candidate loci that emerged from our evolve and re-sequence experiment and tested, (1) whether these loci significantly affected lifespan, (2) the effect size of each locus, and, (3) how these loci mutually interact, i.e. determine the level of epistasis in moulding lifespan. Of the 32 loci, six showed significant main effect associations, of which three loci showed effects of 6.6 days difference in lifespan or larger, while the overall average lifespan was 41.7 days. Eight additional significant pairwise interactions between loci were found, of which four (single) main effects and one three-way interaction was significant. Lastly, we found that alleles that increased lifespan did not necessarily have higher frequencies in populations that showed increased lifespan, indicating that lifespan itself had not been the major target of selection. Our study indicates that individual genotyping following an evolve and re-sequencing study is essential to understand the mechanistic basis of polygenetic adaptation.

The contribution of non-additive genetic effects to the genetic architecture of fitness, and to the evolutionary potential of populations, has been a topic of theoretical and empirical interest for a long time. Yet, the empirical study of these effects in natural populations remains scarce, perhaps because measuring dominance and epistasis relies heavily on experimental line crosses. In this study, we explored the contribution of dominance and epistasis in natural alpine populations of Arabidopsis thaliana, for two fitness traits, the dry biomass and the estimated number of siliques, measured in a greenhouse. We found that, on average, crosses between inbred lines of A. thaliana led to mid-parent heterosis for dry biomass, but outbreeding depression for estimated number of siliques. While heterosis for dry biomass was due to dominance, we found that outbreeding depression for estimated number of siliques could be attributed to the breakdown of beneficial epistatic interactions. We simulated and discussed the implication of these results for the adaptive potential of the studied populations, as well as the use of line-cross analyses to detect non-additive genetic effects.

Climate change poses a significant threat to European beech. These concerns highlight the need to assess the adaptive potential of European beech populations to climate change. Landscape genomics, also known as environmental association analysis, is a powerful tool for identifying gene loci that contribute to local adaptation to environmental pressures. Genotypic data was collected from [~]100 adult beech trees per stand in five locations in the South-Eastern Romanian Carpathians along an altitudinal gradient associated with precipitation and temperature. In total, 53 environmental variables, comprising frost frequency change, temperature and precipitation, were extracted from the climatology data base CHELSA. Based on these variables the Ellenberg-Quotient (EQ) was calculated. We performed environmental association analysis using LFMM (latent factor mixed models) to identify Single Nucleotide Polymorphism (SNP) markers associated with environmental variables and with the principal components calculated based on these. We identified 446 SNP markers significantly associated with the first principal component (PC). These were overlapping with the SNP markers significantly associated with all environmental variables except precipitation accumulated during the growing season. The first PC was correlated with all temperature-based variables and elevation at |r| [~]0.989 to [~]0.997 and with all precipitation-based and Ellenberg-Quotient variables at |r| [~]0.945 to 0.950, except precipitation accumulated during the growing season. A high peak region on chromosome 2 from [~]4.56 to [~]16.27 Mb appeared in all results. This region was [~]3.47 Mb downstream from a region for local adaptation identified by Lazic et al. (2024). In this peak, 273 markers located in the coding region of 22 genes were found. Ten out these 22 were described based on a literature review. Among these ten genes, two may be involved in local adaptation based on our literature review. These two genes are polygalacturonase QRT3-like and NRT1/PTR_FAMILY 5.4-like. The gene polygalacturonase QRT3-like plays a role in pollen development in Arabidopsis thaliana L. and Brassica rapa L. We observed at the corresponding SNP markers, a correlation of the minor allele frequency and temperature-based environmental variables.

DNA methylation variation may play a role in phenotypic variation as it can be directly affected by the environment and be inherited. DNA methylation variations were introduced into the parasite vector snail Biomphalaria glabrata with low genetic diversity by chemical treatment in F0 and followed over 3 generations using epigenetic recombinant inbred lines (epiRILs). We observed phenotypic variation in complex traits such as fecundity and susceptibility to infestation by Schistosoma mansoni and DNA methylation differences in F3. Both, increase and decrease of infestation success (up to 100% and down to 20% prevalence in epiRILs and from 86% to 94% in control RILs) indicated variation in complex resistance/compatibility trait. Average prevalence in control RILs was 84{+/-}5% but only 68{+/-}21 % in epiRILs. Fecundity also changed and was in average 47{+/-}7% in control RILs and 59{+/-}18% in epiRILs, being 12% higher in epiRILs. We found that the heritability h2 of the fecundity in the epiRILs was between 0.5 and 0.6 depending on the method used to estimate it. We developed a model for introducing epimutant offspring snails into resident susceptible populations. If genetic assimilation of the resistant phenotype occured in a small fraction of the introduced epimutant snails, we predict that the susceptible phenotype is replaced by the resistant phenotype after 50-70 generations.

Estimating the extent of genetic differentiation between populations is an important measure in population genetics, ecology and evolutionary biology. Fixation index or FST is an important measure, which is routinely used to quantify this. Previous studies have shown that FST estimated for selectively constrained regions was significantly lower than that estimated for neutral regions. By deriving the theoretical relationship between FST at neutral and constrained sites we show that an excess in the fraction of deleterious variations segregating within populations compared to that segregates between populations is the cause for the reduction in FST estimated at constrained sites. Using whole genome data, our results revealed that the magnitude of reduction in FST estimates obtained for selectively constrained regions was much higher for distantly related populations compared to those estimated for closely related pairs. For example, the reduction was 49% for comparison between European-African populations, 31% for European-Asian comparison, 16% for the Northern-Southern European pair and only 4% for the comparison involving two Southern European (Italian and Spanish) populations. Since deleterious variants are purged over time due to purifying selection, their contribution to the among population diversity at constrained sites decreases with the increase in the divergence between populations. However, within population diversity remain the same for all pairs compared above and therefore FST estimated at constrained sites for distantly related populations are much smaller than those estimated for closely related populations. Our results suggest that the level of population divergence should be considered when comparing constrained site FST estimates obtained for different pairs of populations.

Heat Shock Protein 90 (HSP90) functions as an evolutionary capacitor, allowing populations to store cryptic genetic variation that can be released under stress. While former studies have described the release of morphological variation, its behavioural consequences remain unexplored. In the red flour beetle, Tribolium castaneum, HSP90 inhibition released a phenotype with much smaller, less defined eyes that confers fitness benefits in continuous light and was subsequently assimilated. We hypothesized that altered eye morphology affects light perception and thereby changes light-dependent behaviours. To test whether phenotypes released via evolutionary capacitance can beneficially alter behaviour, we examined locomotor activity rhythm entrainment to light-dark cycles as well as individual and group light choice behaviour. Males of the reduced-eye phenotype exhibited a diminished startle response to sudden light exposure in locomotor activity assays. We also found reduced negative phototaxis in groups of beetles with reduced eyes. This modified behaviour, indicating reduced light sensitivity, may stem from impaired light perception caused by altered eye morphology. Lower light sensitivity could be beneficial under stressful environmental conditions by promoting the exploration of alternative niches. Therefore, this study provides the first evidence for potentially beneficial behavioural changes in a HSP90-released phenotype, reinforcing HSP90s role as an evolutionary capacitor.

O_LIAnimals are often not growing at the maximum rate, but can compensate for a bad start of life by subsequently increasing growth rate. While this compensatory growth is widespread, its direct fitness consequences are seldom investigated and its genetic basis is unknown. C_LIO_LIWe investigated the genetic regulation, as well as fitness and lifespan consequences of compensatory growth in response to temperature, using C. elegans knockout of the thermo-sensitive TRP ion channel TRPA-1, involved in temperature recognition. We exposed juvenile worms to cold, favourable (intermediate) or warm temperatures in order to delay or speed up development. C_LIO_LIWild-type worms initially exposed to cold temperature experienced slower growth but after being switched to a more favourable temperature, they expressed compensatory growth and caught up in size. Those initially reared at warmer temperatures than favourable experienced slower growth and attained smaller adult size after being switched to the most favourable temperature. C_LIO_LICompensatory growth also altered the reproductive schedule. While rate-sensitive individual fitness decreased by cold juvenile temperatures, as a direct effect of the substantial developmental delay, once worms returned to more favourable temperature, they shifted their reproductive schedule towards early reproduction. Therefore, when focusing on the post-treatment period, the reproductive rate increased even though lifetime reproductive success was unaffected. Surprisingly, compensatory growth did not reduce adult lifespan. In contrast to the findings for wild-type worms, juvenile temperature did not induce compensatory or slowed-down growth in the trpa-1 knockout mutants. C_LIO_LIWe thus show that the trpa-1 is involved in the network regulating temperature-induced compensatory growth in C. elegans and that this compensatory growth can influence the reproductive rate. C_LI

A decade of association studies in multiple organisms suggests that most complex traits are polygenic; that is, they have a genetic architecture determined by numerous loci distributed across the genome, each with small effect-size. Thus, determining the degree of polygenicity and its variation across traits, environments and years is useful to understand the genetic basis of phenotypic variation. In this study, we applied multilocus approaches to estimate the degree of polygenicity of fitness-related traits in a long-lived plant (Pinus pinaster Ait., maritime pine) and to analyze how polygenicity changes across environments and years. To do so, we evaluated five categories of fitness-related traits (survival, height, phenology-related, functional, and biotic-stress response traits) in a clonal common garden network, planted in contrasted environments (over 12,500 trees). First, most of the analyzed traits showed evidence of local adaptation based on QST-FST comparisons. Second, we observed a remarkably stable degree of polygenicity, averaging 6% (range of 0-27%), across traits, environments and years. As previously suggested for humans, some of these traits showed also evidence of negative selection, which could explain, at least partially, the high degree of polygenicity. The observed genetic architecture of fitness-related traits in maritime pine supports the polygenic adaptation model. Because polygenic adaptation can occur rapidly, our study suggests that current predictions on the capacity of natural forest tree populations to adapt to new environments should be revised, which is of special relevance in the current context of climate change.

Alleles with opposing effects on fitness characters are said to exhibit selectional antagonistic pleiotropy (broadly construed so that effects are not necessarily confined to the same individual). A number of theoretical investigations considered the case where a pair of alleles at a locus influences two fitness components and derived the conditions giving rise to stable polymorphism under various assumptions about the mode of trait-interaction. Strikingly, many of these analyses concluded that the potential for maintaining polymorphism is strongly constrained by the joint influence of two factors: (1) the prevalence of weak selection coefficients over coefficients of large magnitude, and (2) the absence of beneficial dominance reversals (where the deleterious effects of each allele are partially or completely masked in the heterozygous genotype). Consequently, the conclusion that selective polymorphism is unlikely to be maintained by intralocus mechanisms of antagonistic pleiotropy has achieved widespread acceptance. Here we argue that such conclusions do not apply to any of the following models of antagonism: (i) additive trait-interaction, (ii) multiplicative trait-interaction, (iii) bivoltine selection, (iv) soft selection, (v) hard selection, and (vi) sexual antagonism. We demonstrate that the parameter space giving rise to stable allelic variation is quite large throughout, and moreover, the plenitude of suitable parameters neither depends on the strength of selection nor requires dominance reversal. Dominance coefficients associated with stringent conditions for stable polymorphism are shown to be atypical as compared to all feasible parameters, and best regarded as an outcome of adherence to a special relation: dominance with a constant magnitude and direction, which includes the case of additive allelic effects at a locus. Properties of single-locus equilibria (heterozygosity, allele frequency differentiation) are investigated, as well as the contribution of dominance schemes to the genetic variance in fitness characters in populations at multilocus linkage equilibrium. Author summaryAllelic variants at a locus with opposing effects on multiple fitness components (antagonistic fitness pleiotropy) have long been appreciated as a possible source of balancing selection. The prevalence of polymorphism owing to this form of natural selection, however, has been doubted on theoretical grounds due to the fact that standard assumptions of genetic models (namely, constant magnitudes for the dominance coefficients) are hardly conducive to the maintenance of polymorphism. The major exception to this conclusion lies with schemes that exhibit dominance reversal (where the direction of dominance for antagonistic alleles flips across fitness components). Here we conduct a geometric analysis of the space of polymorphism-promoting dominance parameters and conclude that the conditions for maintaining balanced alleles is unrestrictive, with non-reversals playing an underappreciated role.

The evolutionary potential of organisms depends on the presence of sufficient genetic variation for traits subject to selection, as well as on the genetic covariances among them. While genetic variation ultimately derives from mutation, theory predicts the depletion of genetic (co)variation under consistent directional or stabilizing selection in natural populations. We estimated and compared additive genetic (co)variances for several standard life history traits, including some for which this has never been assessed, before and after 24 generations of artificial selection on male size in the yellow dung fly Scathophaga stercoraria (Diptera: Scathophagidae) using a series of standard half-sib breeding experiments. As predicted, genetic variances (VA), heritabilities (h2) and evolvabilities (IA) of body size, development time, first clutch size, and female age at first clutch were lower after selection. As independent selection lines were crossed prior to testing, we can rule out that this reduction is due to genetic drift. In contrast to the variances, and against expectation, the additive genetic correlations between the sexes for development time and body size remained strong and positive (rA = 0.8-0.9), while the genetic correlation between these traits within the sexes tended to strengthen (but not significantly so). Our study documents that the effect of selection on genetic variance is predictable, whereas that on genetic correlations is not.

Inbreeding depression refers to the reduced fitness of offspring produced by related individuals and is expected to be rare in large outbred populations. When it occurs, marked fitness loss is possible as large populations can carry large loads of recessive harmful mutations which are normally sheltered at the heterozygous state. Using experimental cross data and genome-wide identity-by-descent (IBD) relationships from an outbred marine nine-spined stickleback (Pungitius pungitius) population, we documented a significant decrease in offspring survival probability with increasing parental IBD sharing associated with an average inbreeding load (B) of 15.896. Interestingly, we found that this relationship was also underlined by a positive effect of paternal inbreeding coefficient on offspring survival, suggesting that certain combinations of parental inbreeding and genetic relatedness among mates may promote offspring survival. Apart from demonstrating substantial inbreeding load in an outbred population, the results also highlight the potential caveat associated with artificial establishment of families in experimental studies: wild founder individuals are often - and perhaps mistakenly - assumed to be unrelated.

In this short note, a new unbiased maximum-likelihood estimator is proposed for the recombination frequency in the F2 cross. The estimator is much faster to calculate than its EM algorithm equivalent, yet as efficient. Simulation studies are carried to illustrate the gain over another simple estimate proposed by Benito & Gallego (2004).

The amount of genetic diversity is a key parameter to understand the adaptive potential of populations. It has been demonstrated both theoretically and empirically that several factors influence genetic variance. In angiosperms, two of those are the ploidy level and the mating system of the populations. Polyploidy is theoretically known to increase adaptive potential in the long term. Self-fertilization has been theoretically associated with a decrease in genetic variance, even if it lacks empirical support. These factors have been studied independently, but are often shared in plants. However, there is a lack of empirical studies about the joint effects of polyploidy and selfing on genetic variance. In this paper, we conducted theoretical simulations to explore how genetic diversity could be affected by the ploidy level and mating system. We compared the simulation results with empirical estimates of genetic variance from the plant species Erysimum incanum, a selfing species from the Western Mediterranean basin exhibiting three different ploidy levels. We measured a series of phenotypic traits in individuals of each ploidy, obtained by controlled crosses and grown in different climatic conditions. While theoretical approaches showed a positive relationship between ploidy and genetic variance in both the short and long term, empirical results show lower evolvability and transgressive segregation for polyploids, both results being dependent on environmental conditions. Genetic variance in E. incanum polyploids could be related to recent establishment and adaptation to harsh environments, which explains the apparent contradiction with theory, where more settled and established populations are considered.

The competitive ability of domesticated plants, which may have conferred a fitness advantage in the wild, may result in a reduction of yield in agricultural and forestry contexts, as what matters is the group rather than the individual performance. Traits related to competitive ability can be affected by the presence or absence of related individuals in their neighborhood. Consequently, local relatedness might reveal plant-to-plant interaction that can enhance the predictive abilities of genomic models when accounted for, though it remains difficult to measure. To overcome this difficulty, we analyzed data from the French breeding program of Populus nigra L., where 1,452 genotypes were replicated six to eight times, each time encountering a different neighborhood. We assessed local relatedness and investigated genomic estimated breeding values on tree height and vulnerability to rust with a single-step GBLUP incorporating local relatedness as a covariate. The results indicate that incorporating local relatedness as an additional factor in GBLUP models has a significantly greater influence on resistance to rust than on tree height, though its overall effect on genomic predictions themselves was limited. The influence of local relatedness is small but likely trait-specific, and the genetic architecture of the trait under selection could attenuate or improve the efficacy of breeding for group performance.

Divergence in the evolutionary interests of males and females leads to sexual conflict. Traditionally, sexual conflict has been classified into two types: inter-locus sexual conflict (IeSC) and intra-locus sexual conflict (IaSC). IeSC is modeled as a conflict over outcomes of intersexual reproductive interactions mediated by loci that are sex-limited in their effects. IaSC is thought to be a product of selection acting in opposite directions in males and females on traits with a common underlying genetic basis. While in their canonical formalisms IaSC and IeSC are mutually exclusive, there is growing support for the idea that the two may interact. Empirical evidence for such interactions, however, is limited. Here, we investigated the interaction between IeSC and IaSC in Drosophila melanogaster. Using hemiclonal analysis, we sampled 39 hemigenomes from a laboratory-adapted population of D. melanogaster. We measured the contribution of each hemigenome to adult male and female fitness at three different intensities of IeSC, obtained by varying the operational sex-ratio. Subsequently, we estimated the intensity of IaSC at each sex-ratio by calculating the intersexual genetic correlation for fitness and the proportion of sexually antagonistic fitness-variation. Our results indicate a statistically non-significant trend suggesting that increasing the strength of IeSC ameliorates IaSC in the population.

Meiotic recombination rates vary in response to intrinsic and extrinsic factors. Recently, heat stress has been shown to reveal plasticity in recombination rates in Drosophila pseudoobscura. Here, a combination of molecular genotyping and X-linked recessive phenotypic markers were used to investigate differences in recombination rates due to either heat stress or advanced maternal age. However, haplotype frequencies deviated from equal proportions for crosses using phenotypic markers, indicating viability selection. Interestingly, skews in haplotype frequency were condition-dependent, consistent with the fixation of alleles in the wild type stocks used that are unfit at high temperature. Evidence of viability selection due to heat stress in the wild type haplotypes was most apparent on days 7-9 when more mutant non-crossover haplotypes were recovered in comparison to wild type (p=2.2e-4). Despite the condition-dependent mutational load in both wild type and mutant stocks, an analysis of recombination rate plasticity revealed days 7-9 (p=0.0085) and day 9 (p=0.037) to be significantly higher due to heat stress and days 1-3 as significantly higher due to maternal age (p=0.025). Still, to confirm these findings, SNP genotyping markers were used to further investigate recombination rate. This analysis supported days 9-10 as significantly different due to heat stress in two pairs of consecutive SNP markers (p=0.018; p=0.015), suggesting this time period as when recombination rate is most sensitive to heat stress. This peak timing for recombination plasticity is consistent with D. melanogaster based on comparison of similarly timed key meiotic events, enabling future mechanistic work of temperature stress on recombination rate.

The distribution of pleiotropic mutational effects impacts phenotypic adaptation. However, small effect sizes and high sampling error of covariances hinder investigations of the factors influencing this distribution. Here, we explored the potential for shared information across traits affected by the same mutations to counter sampling error, allowing robust characterisation of patterns of mutational input. Exploiting a published dataset representing 12 samples of the same mutation accumulation experiment in Drosophila serrata, we inferred robust signals of mutational effects from the concordance across samples. Krzanowski common subspace analysis identified a multivariate wing trait with statistically supported mutational variance in all samples. Importantly, this multivariate trait was aligned with the major axis of among-line (mutational) variance within most population samples. That is, despite considerable heterogeneity among samples in individual (co)variance parameter estimates, the predominant pattern of correlated mutational effects was identified in datasets reflecting a typical mutation accumulation experimental design. Two other multivariate traits were statistically supported across most samples. Smaller effect sizes (lower mutational variance) with concomitant larger sampling error or other factors (e.g., microenvironmental dependence of effects) may reduce the robustness of estimated mutational input for these traits. Overall, our results suggest sampling error does not preclude multivariate analyses of mutation accumulation experiments from extending our knowledge of pleiotropic mutational effects.

Sexually antagonistic (SA) selection, favouring different alleles in males and females, can contribute to the maintenance of genetic diversity. Current theory predicts that biallelic polymorphism can be maintained in SA loci under strong selection or dominance reversal in the sexes. Yet, selection should often be weak, several candidate SA loci harbour more than two segregating alleles and dominance reversal may not be common. We present a general model to explore the evolution of alleles at autosomal and X-linked loci under SA selection, affecting a quantitative trait with distinct female and male optima. We confirm that additive allelic effects predict biallelic polymorphism, but only under symmetric and relatively strong selection. However, polyallelic polymorphism can evolve under conditions of sex-specific or X-linked dominance for the trait, particularly under weak selection, such that several alleles coexist in a single population through balancing selection. Our analysis furthermore shows that sex-specific dominance and X-linked dominance evolve when permitted, thus polyallelic polymorphism is a likely evolutionary outcome. We conclude that SA selection can drive the co-evolution of differences in dominance between the sexes and polyallelic polymorphism, particularly under weak selection, an outcome reducing the gender load. To assess these findings, we analyse segregating variation in three populations of an insect model system and find that (1) loci with the strongest signal of polyallelic polymorphism are enriched with functions associated with known SA phenotypes and (2) both candidate SA loci and loci exhibiting sex-specific dominance show a stronger signal of polyallelic polymorphism.

Natural climate change and recent anthropogenic activities have largely contributed to habitat loss and fragmentation across the world, leading to 70% of worldwide remaining forests to be within 1 km of forests edges (Haddad et al., 2015). Ecological studies have shown that edge-effect influences ecological communities, species richness and abundance across many taxa, contributing to worldwide decline in biodiversity. Since edge-effect reduces species abundance and connectivity, it is also expected to negatively influence species genetic variation. In fact, previous theoretical studies had showed that populations closer to the edges of a finite stepping-stone model tends to have shorter coalescence times, and therefore, lower genetic diversity, than central populations. However, predicting the impact of edge effect on local genetic diversity remains challenging in realistic and more complex habitat fragments, where the additive effect of multiple edges is expected to take place. In the present study we explore the genetic consequence of habitat loss at the scale of a habitat fragment (patch-scale), looking at the interplay between patch-size and edge-effect on spatial genetic diversity. We propose a statistical approach to estimate edge-impacted effective population size from habitat cover information and use this measure to predict spatial genetic diversity in both equilibrium and non-equilibrium populations. We address these questions using spatially-explicit simulations and propose a spatially-explicit analytical framework able to model spatio-temporal changes in genetic diversity due to edge-effect and habitat loss.

In Drosophila, comparisons of the thermal plasticity of pigmentation across serially homologous abdominal segments have been conducted in two species, namely Drosophila melanogaster and D. kikkawai. Pigmentation variation has different genetic architecture in the two species, being oligogenic in the former and monogenic in the later. Here, we analyze the thermal plasticity of abdominal pigmentation in a third species, D. erecta, which is phylogenetically close to D. melanogaster but like D. kikkawai has a monogenic basis for pigmentation variation. However, the underlying locus differs between D. erecta and D. kikkawai, being the X-linked melanin-synthesis gene tan in the former and the autosomal transcription factor pdm3 in the later. We found that in spite of a low overall plasticity in monogenic species compared to D. melanogaster, the two monogenic species showed divergent plasticity patterns in respect to the response to temperature and to the degree of dominance in heterozygotes. Those results provide new insights on the dependence of the degree of plasticity on the genetic architecture as well as on the extent of phenotypic convergence.