Stability of the G-matrix in a population experiencing pleiotropic mutation, stabilizing selection, and genetic drift

Abstract. Quantitative genetics theory provides a framework that predicts the effects of selection on a phenotype consisting of a suite of complex traits. However, the ability of existing theory to reconstruct the history of selection or to predict the future trajectory of evolution depends upon the evolutionary dynamics of the genetic variance-covariance matrix (G-matrix). Thus, the central focus of the emerging field of comparative quantitative genetics is the evolution of the G-matrix. Existing analytical theory reveals little about the dynamics of G, because the problem is too complex to be mathematically tractable. As a first step toward a predictive theory of G-matrix evolution, our goal was to use stochastic computer models to investigate factors that might contribute to the stability of G over evolutionary time. We were concerned with the relatively simple case of two quantitative traits in a population experiencing stabilizing selection, pleiotropic mutation, and random genetic drift. Our results show that G-matrix stability is enhanced by strong correlational selection and large effective population size. In addition, the nature of mutations at pleiotropic loci can dramatically influence stability of G. In particular, when a mutation at a single locus simultaneously changes the value of the two traits (due to pleiotropy) and these effects are correlated, mutation can generate extreme stability of G. Thus, the central message of our study is that the empirical question regarding G-matrix stability is not necessarily a general question of whether G is stable across various taxonomic levels. Rather, we should expect the G-matrix to be extremely stable for some suites of characters and unstable for others over similar spans of evolutionary time.     

Pervasive,yet idiosyncratic,epistatic pleiotropy during adaptation in a behaviourally complex microbe

Understanding how multiple mutations interact to jointly impact multiple ecologically important traits is critical for creating a robust picture of organismal fitness and the process of adaptation. However, this is complicated by both environmental heterogeneity and the complexity of genotype‐to‐phenotype relationships generated by pleiotropy and epistasis. Moreover, little is known about how pleiotropic and epistatic relationships themselves change over evolutionary time. The soil bacterium Myxococcus xanthus employs several distinct social traits across a range of environments. Here, we use an experimental lineage of M. xanthus that evolved a novel form of social motility to address how interactions between epistasis and pleiotropy evolve. Specifically, we test how mutations accumulated during selection on soft agar pleiotropically affect several other social traits (hard agar motility, predation and spore production). Relationships between changes in swarming rate in the selective environment and the four other traits varied greatly over time in both direction and magnitude, both across timescales of the entire evolutionary lineage and individual evolutionary time steps. We also tested how a previously defined epistatic interaction is pleiotropically expressed across these traits. We found that phenotypic effects of this epistatic interaction were highly correlated between soft and hard agar motility, but were uncorrelated between soft agar motility and predation, and inversely correlated between soft agar motility and spore production. Our results show that ‘epistatic pleiotropy’ varied greatly in magnitude, and often even in sign, across traits and over time, highlighting the necessity of simultaneously considering the interacting complexities of pleiotropy and epistasis when studying the process of adaptation.     

Selective Pressure Causes an RNA Virus to Trade Reproductive Fitness for Increased Structural and Thermal Stability of a Viral Enzyme

The modulation of fitness by single mutational substitutions during environmental change is the most fundamental consequence of natural selection. The antagonistic tradeoffs of pleiotropic mutations that can be selected under changing environments therefore lie at the foundation of evolutionary biology. However, the molecular basis of fitness tradeoffs is rarely determined in terms of how these pleiotropic mutations affect protein structure. Here we use an interdisciplinary approach to study how antagonistic pleiotropy and protein function dictate a fitness tradeoff. We challenged populations of an RNA virus, bacteriophage Φ6, to evolve in a novel temperature environment where heat shock imposed extreme virus mortality. A single amino acid substitution in the viral lysin protein P5 (V207F) favored improved stability, and hence survival of challenged viruses, despite a concomitant tradeoff that decreased viral reproduction. This mutation increased the thermostability of P5. Crystal structures of wild-type, mutant, and ligand-bound P5 reveal the molecular basis of this thermostabilization—the Phe207 side chain fills a hydrophobic cavity that is unoccupied in the wild-type—and identify P5 as a lytic transglycosylase. The mutation did not reduce the enzymatic activity of P5, suggesting that the reproduction tradeoff stems from other factors such as inefficient capsid assembly or disassembly. Our study demonstrates how combining experimental evolution, biochemistry, and structural biology can identify the mechanisms that drive the antagonistic pleiotropic phenotypes of an individual point mutation in the classic evolutionary tug-of-war between survival and reproduction.     

Consequences of host adaptation for performance of vesicular stomatitis virus in novel thermal environments

Although it is widely assumed that the selective advantage of niche specialization drives species biodiversity, some theory suggests that generalists are favored over specialists when environments change unexpectedly. But this idea is rarely tested empirically, and its relevance is unknown for microparasites such as RNA viruses. Due to their small genome sizes pleiotropy is not uncommon in RNA viruses. Therefore, the genetic architectures underlying generalist traits may be indirectly molded by selection to better prepare generalist organisms for growth in new environments. Previously, vesicular stomatitis viruses were evolved to specialize on a single host, or to generalize on multiple hosts. Here we test whether virus generalists arising in the context of host adaptation also perform differently than specialists when viruses grow at novel temperatures. We compared thermal reaction norms of performance, within and among groups of viral specialists and generalists. Results showed that host adaptation was consequential for some fitness traits at novel temperatures due to modification of pleiotropic viral genes. Contrary to theoretical predictions, host generalists were selectively disadvantaged at extreme cool and warm environments. Multi-host adaptation may compromise the evolved thermostability of viral proteins, creating a cost of host generalization when viruses replicate at extreme temperatures.     

Complete alanine scanning of intersubunit interfaces in a foot-and-mouth disease virus capsid reveals critical contributions of many side chains to particle stability and viral function

Spherical virus capsids are large, multimeric protein shells whose assembly and stability depend on the establishment of multiple non-covalent interactions between many polypeptide subunits. In a foot-and-mouth disease virus capsid, 42 amino acid side chains per protomer are involved in noncovalent interactions between pentameric subunits that function as assembly/disassembly intermediates. We have individually truncated to alanine these 42 side chains and assessed their relevance for completion of the virus life cycle and capsid stability. Most mutations provoked a drastic reduction in virus yields. Nearly all of these critical mutations led to virions whose thermal inactivation rates differed from that of the parent virus, and many affected also early steps in the viral cycle. Rapid selection of genotypic revertants or variants with forward or compensatory mutations that restored viability was occasionally detected. The results with this model virus indicate the following. (i). Most of the residues at the interfaces between capsid subunits are critically important for viral function, in part but not exclusively because of their involvement in intersubunit recognition. Each hydrogen bond and salt bridge buried at the subunit interfaces may be important for capsid stability. (ii). New mutations able to restore viability may arise frequently at the subunit interfaces during virus evolution. (iii). A few interfacial side chains are functionally tolerant to truncation and may provide adequate mutation sites for the engineering of a thermostable capsid, potentially useful as an improved vaccine.     

Fluctuating Selection Models and Mcdonald-Kreitman Type Analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates.     

Changing Folding and Binding Stability in a Viral Coat Protein: A Comparison between Substitutions Accessible through Mutation and Those Fixed by Natural Selection

Previous studies have shown that most random amino acid substitutions destabilize protein folding (i.e. increase the folding free energy). No analogous studies have been carried out for protein-protein binding. Here we use a structure-based model of the major coat protein in a simple virus, bacteriophage φX174, to estimate the free energy of folding of a single coat protein and binding of five coat proteins within a pentameric unit. We confirm and extend previous work in finding that most accessible substitutions destabilize both protein folding and protein-protein binding. We compare the pool of accessible substitutions with those observed among the φX174-like wild phage and in experimental evolution with φX174. We find that observed substitutions have smaller effects on stability than expected by chance. An analysis of adaptations at high temperatures suggests that selection favors either substitutions with no effect on stability or those that simultaneously stabilize protein folding and slightly destabilize protein binding. We speculate that these mutations might involve adjusting the rate of capsid assembly. At normal laboratory temperature there is little evidence of directional selection. Finally, we show that cumulative changes in stability are highly variable; sometimes they are well beyond the bounds of single substitution changes and sometimes they are not. The variation leads us to conclude that phenotype selection acts on more than just stability. Instances of larger cumulative stability change (never via a single substitution despite their availability) lead us to conclude that selection views stability at a local, not a global, level.     

Alleles in metabolic and oxygen‐sensing genes are associated with antagonistic pleiotropic effects on life history traits and population fitness in an ecological model insect*

Genes with opposing effects on fitness at different life stages are the mechanistic basis for evolutionary theories of aging and life history. Examples come from studies of mutations in model organisms, but there is little knowledge of genetic bases of life history tradeoffs in natural populations. Here, we test the hypothesis that alleles affecting oxygen sensing in Glanville fritillary butterflies have opposing effects on larval versus adult fitness‐related traits. Intermediate‐frequency alleles in Succinate dehydrogenase d, and to a lesser extent Hypoxia inducible factor 1α, are associated in larvae with variation in metabolic rate and activation of the hypoxia inducible factor (HIF) pathway, which affects tracheal development and delivery of oxygen to adult flight muscles. A dominant Sdhd allele is likely to cause antagonistic pleiotropy for fitness through its opposing effects on larval metabolic and growth rate versus adult flight and dispersal, and may have additional effects arising from sensitivity to low‐iron host plants. Prior results in Glanville fritillaries indicate that fitness of alleles in Sdhd and another antagonistically pleiotropic metabolic gene, Phosphoglucose isomerase, depend strongly on the size and distribution of host plant patches. Hence, these intermediate‐frequency alleles are involved in ecoevolutionary dynamics involving life history tradeoffs.     

Can indirect selection and genetic context contribute to trait diversification? A transition‐probability study of blossom‐colour evolution in two genera

Darwin recognized that biological diversity has accumulated as a result of both adaptive and nonadaptive processes. Very few studies, however, have addressed explicitly the contribution of nonadaptive processes to evolutionary diversification, and no general procedures have been established for distinguishing between adaptive and nonadaptive processes as sources of trait diversity. I use the diversification of flower colour as a model system for attempting to identify adaptive and nonadaptive causes of trait diversification. It is widely accepted that variation in flower colour reflects direct, adaptive response to divergent selective pressures generated by different pollinators. However, diversification of flower colour may also result from the effects of nonadaptive, pleiotropic relationships with vegetative traits. Floral pigments that have pleiotropic relationships to vegetative pigments may evolve and diversify in at least two nonadaptive ways. (1) Indirect response to selection on the pleiotropically related nonfloral traits may occur (indirect selection). (2) Divergent evolution in response to parallel selective pressures (e.g. selection by pollinators for visually obvious flowers) may occur because populations are at different genetic starting points, and each population follows its own genetic `line of least resistance.' A survey of literature suggests that pleiotropic relationships between flower colour and vegetative traits are common. Phylogenetically informed analyses of comparative data from Dalechampia (Euphorbiaceae) and Acer (Aceraceae), based on trait‐transition probabilities and maximum likelihood, indicated that floral and vegetative pigments are probably pleiotropically related in these genera, and this relationship better explains the diversification of floral colour than does direct selection by pollinators. In Dalechampia pink/purple floral bract colour may have originated by indirect response to selection on stem and leaf pigments. In Acer selection by pollinators for visually obvious flowers may to have led to the evolution of red or purple flowers in lineages synthesizing and deploying red anthocyanins in leaves, and pale‐green or yellow flowers in species not deploying red anthocyanins in vegetative structures. This study illustrates the broader potential of indirect selection and parallel selection on different genetic starting points to contribute to biological diversity, and the value of testing directly for the operation of these nonadaptive diversifying processes.     

Fluctuating selection on reproductive timing in Digitalis purpurea

Despite recent, strong interest in the modelling of monocarpic perennial flowering strategies, little is known about how variation in demographic rates affects selection on optimal timing of flowering. Temporal variation may yield fluctuating selective pressures, or, if individuals experience time trends, selection for phenotypic plasticity. Here we report the results of a 3-year study in a large field population of the facultative biennial herb Digitalis purpurea , where we use field data on size-dependent growth, survival and fecundity to parameterize an existing optimisation model. We compare results from models using either deterministic or individually varying demographic rates to address the degree of fluctuating selection on the flowering strategy. In addition, we explore whether recent growing conditions influence the size-specific liability to flower. Model results differed widely between years; immediate onset of reproduction was predicted in 1999, strongly delayed reproduction in 2000. This reflected large differences in both growth and survival rates between years. Observed flowering sizes also varied between years, but were larger in 1999 than in 2000, contrary to model predictions. Incorporating individual variation in growth increased predicted optimal flowering sizes compared to models using deterministic growth, whereas the inclusion of individual survival variation had little effect. There was no significant effect of recent growth rate on flowering probability. Taken together, these results indicate highly fluctuating selection on the flowering strategy in D. purpurea , but no evidence of adaptive plasticity in response to current growing conditions. Fluctuating selection may contribute to maintain genetic variation for threshold size for flowering, and may partly explain the large within-season size-variation in flowering individuals found in natural populations of D. purpurea .     

Pleiotropic Mutations Are Subject to Strong Stabilizing Selection

The assumption that pleiotropic mutations are more deleterious than mutations with more restricted phenotypic effects is an important premise in models of evolution. However, empirical evidence supporting this assumption is limited. Here, we estimated the strength of stabilizing selection on mutations affecting gene expression in male Drosophila serrata. We estimated the mutational variance (V_M) and the standing genetic variance (V_G) from two well-matched panels of inbred lines: a panel of mutation accumulation (MA) lines derived from a single inbred ancestral line and a panel of inbred lines derived from an outbred population. For 855 gene-expression traits, we estimated the strength of stabilizing selection as s = V_M/V_G. Selection was observed to be relatively strong, with 17% of traits having s > 0.02, a magnitude typically associated with life-history traits. Randomly assigning expression traits to five-trait sets, we used factor analytic mixed modeling in the MA data set to identify covarying traits that shared pleiotropic mutations. By assigning traits to the same trait sets in the outbred line data set, we then estimated s for the combination of traits affected by pleiotropic mutation. For these pleiotropic combinations, the median s was three times greater than s acting on the individual component traits, and 46% of the pleiotropic trait combinations had s > 0.02. Although our analytical approach was biased toward detecting mutations with relatively large effects, likely overestimating the average strength of selection, our results provide widespread support for the prediction that stronger selection can act against mutations with pleiotropic effects.THE extent to which new mutations have pleiotropic effects on multiple traits, and ultimately on fitness is central to our understanding of the maintenance of genetic variation and the process of adaptation (Kondrashov and Turelli 1992; Otto 2004; Johnson and Barton 2005; Zhang and Hill 2005). Analyses of Fisher’s (1930) geometric model of adaptation have shown that a mutation with effects on many traits will have a reduced probability of contributing to adaptive evolution (Orr 2000; Welch and Waxman 2003; see also Haygood 2006). For a population close to its optimum under mutation–selection balance, a direct corollary of this is that selection must act more strongly against mutations with wider pleiotropic effects (Zhang 2012).Evidence for the strength of selection increasing with the number of traits that are pleiotropically affected by a mutation is limited. At a phenotypic level, nonlinear (stabilizing) selection is much stronger on combinations of metric traits than on each individual trait contributing to the combination (Blows and Brooks 2003; Walsh and Blows 2009). Given that genetic correlations among such traits are expected to be a consequence of pleiotropic alleles (Lande 1980), stronger selection on trait combinations is consistent with stronger selection on pleiotropic mutations that are likely to underlie the genetic covariance among such traits. There is some evidence that per-trait allelic effects might be greater for alleles with more widespread pleiotropic effects (Wagner et al. 2008; Wang et al. 2010); as mutations with larger phenotypic effects might be more effectively targeted by selection, this also suggests stronger selection against more pleiotropic mutation.Mutation accumulation (MA) breeding designs, in which the opportunity for selection is reduced, allowing new mutations to drift to fixation, provide an opportunity to characterize the strength of selection acting directly against new mutations. Rice and Townsend (2012) proposed an approach for determining the strength of selection acting against mutations at individual loci, combining information from QTL mapping and MA studies. This approach could conceivably be extended to associate the strength of selection with the number of traits a QTL affects. More typically, estimates of selection from MA designs are focused on traits, rather than alleles. Under the assumption that most mutations are deleterious, an assumption supported by MA studies (Halligan and Keightley 2009), the strength of selection acting on mutations affecting quantitative traits can be measured as the ratio of the mutational to the standing genetic variance, s = V_M/V_G, where s is the selection coefficient of the mutation in heterozygous form (Barton 1990; Houle et al. 1996). While estimating s in this way provides a framework for estimating selection on pleiotropic combinations of traits, we are not aware of any studies adopting this approach to directly estimate the strength of selection acting on mutations affecting multiple traits.Within an MA framework, Estes and Phillips (2006) manipulated the opportunity for selection, providing rare direct evidence of stronger selection against mutations with pleiotropic effects. In a DNA repair-deficient strain of Caenorhabditis elegans, Estes and Phillips (2006) observed lower mutational covariance among life-history components when selection was allowed (larger populations) than when the opportunity for selection was limited (small populations). Similarly, McGuigan et al. (2011) compared Drosophila serrata MA lines accumulating mutations in the presence or absence of sexual selection on males, reporting reduced covariance between two fitness components in the selection treatment. These studies reveal that selection can eliminate nonlethal alleles with pleiotropic effects, but whether traits other than life-history components exhibit similar evidence of selection against pleiotropic alleles remains unknown.In parallel to the quantitative genetic predictions that pleiotropic alleles will be under stronger selection, molecular genetic theory predicts that the rate of gene evolution will be negatively correlated with pleiotropy (Pal et al. 2006; Salathe et al. 2006). More highly pleiotropic genes, as identified through the extent of connectivity (the number of interactions) in protein–protein interaction networks (Jeong et al. 2001), or the number of gene ontology (GO) terms (Jovelin and Phillips 2009) are more likely to be essential (i.e., knockout mutations result in lethality), suggesting that selection is stronger against large-effect (knockout) mutations in more highly pleiotropic genes. However, the selection acting against small-effect, nonlethal mutations in pleiotropic genes is less clear (Pal et al. 2006). Several studies have found an association between gene pleiotropy indices, such GO annotation of the number of biological processes or tissue specificity of expression, and the rate of sequence evolution (e.g., Pal et al. 2001; Salathe et al. 2006; Jovelin and Phillips 2009; Su et al. 2010). These pleiotropy indices typically explain little of the variation in sequence evolutionary rates, and it remains unclear whether more highly pleiotropic mutations are typically under stronger selection (Pal et al. 2006; Salathe et al. 2006).Here, we estimate the selection coefficients acting against naturally occurring mutations affecting gene-expression traits in male D. serrata to quantitatively test if selection is stronger on mutations that affect multiple traits. Gene-expression phenotypes are uniquely positioned to enable detailed investigations of pleiotropy: there are many of them, they represent a broad coverage of biological function, they can be analyzed to quantify developmental pleiotropy in the same way as traits traditionally considered in quantitative genetics, and GO information can be used to index molecular genetic pleiotropy. We use multivariate mixed-model analyses of expression traits in a set of inbred lines from a mutation accumulation experiment to estimate the mutational variance in individual expression traits, and the pleiotropic mutational covariance among random sets of five expression traits. Using a second panel of inbred lines, derived from a natural, outbred, population, we estimate the standing genetic variance in the same individual traits and five-trait combinations. From these estimates of mutational and standing genetic variance, we calculate s for each of the individual traits and trait combinations to determine whether selection has typically been stronger on mutations with pleiotropic effects than on other mutations affecting each trait. We complement this quantitative genetic analysis of developmental pleiotropy with an analysis of molecular genetic pleiotropy (Paaby and Rockman 2013), determining whether the strength of selection acting on individual expression traits can be predicted from the number of biological functions that the gene annotates to in the GO database or to the range of tissues in which the gene is expressed.     

Facial attractiveness,developmental stability,and fluctuating asymmetry

Despite robust cross-cultural reliability of human facial attractiveness ratings, research on facial attractiveness has only superficially addressed the connection between facial attractiveness and the history of sexual selection in Homo sapiens. There are reasons to believe that developmental stability and phenotypic quality are related. Recent studies of nonhuman animals indicate that developmental stability, measured as fluctuating asymmetry in generally bilateral symmetrical traits, is predictive of performance in sexual selection: Relatively symmetrical males are advantaged under sexual selection. This pattern is suggested by our study of facial attractiveness and fluctuating asymmetry in seven bilateral body traits in a student population. Overall, facial attractiveness negatively correlated with fluctuating asymmetry; the relation for men, but not for women, was statistically reliable. Possible confounding factors were controlled for in the analysis.     

Phenotypic integration and the potential for independent color evolution in a polymorphic spring ephemeral

The genetic architecture of the total phenotype may substantially constrain or enhance the evolution of floral color within populations in response to multiple selection pressures. Using Claytonia virginica I previously identified opposing selection on floral color generated through herbivores and pathogens. Here I ask whether the evolution of floral color in this system is constrained or unconstrained by its phenotypic integration with floral and vegetative traits. Morphological, physiological, and pollen traits were measured on over 400 plants in the field and greenhouse, and these data were used to test whether floral-color morphs differed with respect to other traits and whether the among-trait correlation structure differed across the color morphs. The color morphs varied with respect to most measured traits; however, the pattern of variation was not consistent among them, and there was little evidence of trade-offs with floral color. A common principal components analysis revealed that the pattern of phenotypic integration substantially differed among the color morphs. Combined, these results suggest that floral-color evolution may proceed relatively unconstrained by associations with other traits in this system. The absence of a strong constraint in combination with known fluctuating selective pressures may help to explain observed within- and among-population color variation in this species.     

Sex, ecology and the brain: evolutionary correlates of brain structure volumes in Tanganyikan cichlids

Analyses of the macroevolutionary correlates of brain structure volumes allow pinpointing of selective pressures influencing specific structures. Here we use a multiple regression framework, including phylogenetic information, to analyze brain structure evolution in 43 Tanganyikan cichlid species. We analyzed the effect of ecological and sexually selected traits for species averages, the effect of ecological traits for each sex separately and the influence of sexual selection on structure dimorphism. Our results indicate that both ecological and sexually selected traits have influenced brain structure evolution. The patterns observed in males and females generally followed those observed at the species level. Interestingly, our results suggest that strong sexual selection is associated with reduced structure volumes, since all correlations between sexually selected traits and structure volumes were negative and the only statistically significant association between sexual selection and structure dimorphism was also negative. Finally, we previously found that monoparental female care was associated with increased brain size. However, here cerebellum and hypothalamus volumes, after controlling for brain size, associated negatively with female-only care. Thus, in accord with the mosaic model of brain evolution, brain structure volumes may not respond proportionately to changes in brain size. Indeed selection favoring larger brains can simultaneously lead to a reduction in relative structure volumes.     

Negative clonal selection in tumor evolution

Development of cancer requires the acquisition of multiple oncogenic mutations and selection of the malignant clone. Cancer evolves within a finite host lifetime and mechanisms of carcinogenesis that accelerate this process may be more likely to contribute to the development of clinical cancers. Mutator mutations are mutations that affect genome stability and accelerate the acquisition of oncogenic mutations. However, mutator mutations will also accelerate the accumulation of mutations that decrease cell proliferation, increase apoptosis, or affect other key fitness parameters. These "reduced-fitness" mutations may mediate "negative clonal selection," i.e., selective elimination of premalignant mutator clones. Target reduced-fitness loci may be "recessive" (both copies must be mutated to reduce fitness) or "dominant" (single-copy mutation reduces fitness). A direct mathematical analysis is applied to negative clonal selection, leading to the conclusion that negative clonal selection against mutator clones is unlikely to be a significant effect under realistic conditions. In addition, the relative importance of dominant and recessive reduced-fitness mutations is quantitatively defined. The relative predominance of mutator mutations in clinical cancers will depend on several variables, including the tolerance of the genome for reduced-fitness mutations, particularly the number and potency of dominant reduced-fitness loci.     

Differential selection of growth rate-related traits in wild barley, Hordeum spontaneum, in contrasting greenhouse nutrient environments

Across-species comparisons show that inherent variation in relative growth rate (RGR) and its underlying traits are correlated with habitat productivity. In this study, we test the hypothesis that growth rate-related traits confer differential selective effects in contrasting nutrient environments. We specifically test whether high RGR is targeted by selection in nutrient-rich environments whereas low values of traits that underlie RGR [specific leaf area (SLA), leaf mass fraction and leaf area ratio (LAR)] confer a direct fitness advantage in nutrient-poor environments, resulting in selection of low RGR as a correlated response. We measured RGR, its underlying component traits, and estimated fitness in a range of wild barley (Hordeum spontaneum) accessions grown under high and low nutrient conditions. Selection on component traits differed between the two environments, while total selection of RGR was not significant. Using multiple regression and path analysis to estimate direct fitness effects, a selective advantage of high LAR and SLA was demonstrated only under nutrient-rich conditions. While supporting the view that observed associations between habitat richness and some RGR-component traits reflect adaptation to differing nutrient regimes, our data suggest that direct selection targets component traits rather than RGR itself.     

Apparent directional selection by biased pleiotropic mutation

Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.     

The genetic architecture of domestication in the chicken: effects of pleiotropy and linkage

The extent of pleiotropy and epistasis in quantitative traits remains equivocal. In the case of pleiotropy, multiple quantitative trait loci are often taken to be pleiotropic if their confidence intervals overlap, without formal statistical tests being used to ascertain if these overlapping loci are statistically significantly pleiotropic. Additionally, the degree to which the genetic correlations between phenotypic traits are reflected in these pleiotropic quantitative trait loci is often variable, especially in the case of antagonistic pleiotropy. Similarly, the extent of epistasis in various morphological, behavioural and life-history traits is also debated, with a general problem being the sample sizes required to detect such effects. Domestication involves a large number of trade-offs, which are reflected in numerous behavioural, morphological and life-history traits which have evolved as a consequence of adaptation to selective pressures exerted by humans and captivity. The comparison between wild and domestic animals allows the genetic analysis of the traits that differ between these population types, as well as being a general model of evolution. Using a large F(2) intercross between wild and domesticated chickens, in combination with a dense SNP and microsatellite marker map, both pleiotropy and epistasis were analysed. The majority of traits were found to segregate in 11 tight 'blocks' and reflected the trade-offs associated with domestication. These blocks were shown to have a pleiotropic 'core' surrounded by more loosely linked loci. In contrast, epistatic interactions were almost entirely absent, with only six pairs identified over all traits analysed. These results give insights both into the extent of such blocks in evolution and the development of domestication itself.     

Constraints on adaptive mutations in the codling moth Cydia pomonella (L.): measuring fitness trade-offs and natural selection

Adaptive changes in populations encountering a new environment are often constrained by deleterious pleiotropic interactions with ancestral physiological functions. Evolutionary responses of populations can thus be limited by natural selection under fluctuating environmental conditions, if the adaptive mutations are associated with pleiotropic fitness costs. In this context, we have followed the evolution of the frequencies of insecticide-resistant mutants of Cydia pomonella when reintroduced into an untreated environment. The novel set of selective forces after removal of insecticide pressure led to the decline of the frequencies of resistant phenotypes over time, suggesting that the insecticide-adapted genetic variants were selected against the absence of insecticide (with a selective coefficient estimated at 0.11). The selective coefficients were also estimated for both the major cytochrome P450-dependent monooxygenase (MFO) and the minor glutathione S-transferase (GST) systems (0.17 and negligible, respectively), which have been previously shown to be involved in resistance. The involvement of metabolic systems acting both through xenobiotic detoxification and biosynthetic pathways of endogenous compounds may be central to explaining the deleterious physiological consequences resulting from pleiotropy of adaptive changes. The estimation of the magnitude of the fitness cost associated with insecticide resistance in C. pomonella suggests that resistance management strategies exclusively based on insecticide alternations would be unlikely to delay such a selection process.     

Variable pleiotropic effects from mutations at the same locus hamper prediction of fitness from a fitness component

The relationship of genotype, fitness components, and fitness can be complicated by genetic effects such as pleiotropy and epistasis and by heterogeneous environments. However, because it is often difficult to measure genotype and fitness directly, fitness components are commonly used to estimate fitness without regard to genetic architecture. The small bacteriophage X174 enables direct evaluation of genetic and environmental effects on fitness components and fitness. We used 15 mutants to study mutation effects on attachment rate and fitness in six hosts. The mutants differed from our lab strain of X174 by only one or two amino acids in the major capsid protein (gpF, sites 101 and 102). The sites are variable in natural and experimentally evolved X174 populations and affect phage attachment rate. Within the limits of detection of our assays, all mutations were neutral or deleterious relative to the wild type; 11 mutants had decreased host range. While fitness was predictable from attachment rate in most cases, 3 mutants had rapid attachment but low fitness on most hosts. Thus, some mutations had a pleiotropic effect on a fitness component other than attachment rate. In addition, on one host most mutants had high attachment rate but decreased fitness, suggesting that pleiotropic effects also depended on host. The data highlight that even in this simple, well-characterized system, prediction of fitness from a fitness component depends on genetic architecture and environment.