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67 results for “pleiotropy”
Data from: A benign juvenile environment reduces the strength of antagonistic pleiotropy and genetic variation in the rate of senescence
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Data from: Apolipoprotein (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?
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Data from: Antagonistic pleiotropy and mutation accumulation contribute to age-related decline in stress response
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Data from: Adaptation via pleiotropy and linkage: association mapping reveals a complex genetic architecture within the stickleback Eda locus
Genomic mapping of the loci associated with phenotypic evolution has revealed genomic "hotspots", or regions of the genome that control multiple phenotypic traits. This clustering of loci has important implications for the speed and maintenance of adaptation and could be due to pleiotropic effects of a single mutation or tight genetic linkage of multiple causative mutations affecting different traits. The threespine stickleback (<i>Gasterosteus aculeatus</i>) is a powerful model for the study of adaptive evolution because the marine ecotype has repeatedly adapted to freshwater environments across the northern hemisphere in the last 12,000 years. Freshwater ecotypes have repeatedly fixed a 16 kilobase haplotype on chromosome IV that contains Ectodysplasin (<i>Eda</i>), a gene known to affect multiple traits, including defensive armor plates, lateral line sensory hair cells, and schooling behavior. Many additional traits have previously been mapped to a larger region of chromosome IV that encompasses the <i>Eda</i> freshwater haplotype. To identify which of these traits specifically map to this adaptive haplotype, we made crosses of rare marine fish heterozygous for the freshwater haplotype in an otherwise marine genetic background. Further, we performed fine-scale association mapping in a fully interbreeding, polymorphic population of freshwater stickleback to disentangle the effects of pleiotropy and linkage on the phenotypes affected by this haplotype. Although we find evidence that linked mutations have small effects on a few phenotypes, a small 1.4 kb region within the first intron of <i>Eda</i> has large effects on three phenotypic traits: lateral plate count, and both the number and patterning of the posterior lateral line neuromasts. Thus, the <i>Eda</i> haplotype is a hotspot of adaptation in stickleback due to both a small, pleiotropic region affecting multiple traits as well as multiple linked mutations affecting additional traits.
Data from: What affects the predictability of evolutionary constraints using a G-matrix? The relative effects of modular pleiotropy and mutational correlation
Phenotypic traits do not always respond to selection independently from each other and often show correlated responses to selection. The structure of a genotype-phenotype map (GP map) determines trait covariation, which involves variation in the degree and strength of the pleiotropic effects of the underlying genes. It is still unclear, and debated, how much of that structure can be deduced from variational properties of quantitative traits that are inferred from their genetic (co)variance matrix (G-matrix). Here we aim to clarify how the extent of pleiotropy and the correlation among the pleiotropic effects of mutations differentially affect the structure of a G-matrix and our ability to detect genetic constraints from its eigen decomposition. We show that the eigenvectors of a G-matrix can be predictive of evolutionary constraints when they map to underlying pleiotropic modules with correlated mutational effects. Without mutational correlation, evolutionary constraints caused by the fitness costs associated with increased pleiotropy are harder to infer from evolutionary metrics based on a G-matrix's geometric properties because uncorrelated pleiotropic effects do not affect traits' genetic correlations. Correlational selection induces much weaker modular partitioning of traits' genetic correlations in absence then in presence of underlying modular pleiotropy.
Data from: Antagonistic pleiotropy in species with separate sexes, and the maintenance of genetic variation in life-history traits and fitness
Antagonistic pleiotropy (AP) – where alleles of a gene increase some components of fitness at a cost to others – can generate balancing selection, and contribute to the maintenance of genetic variation in fitness traits, such as survival, fecundity, fertility, and mate competition. Previous theory suggests that AP is unlikely to maintain variation unless antagonistic selection is strong, or AP alleles exhibit pronounced differences in genetic dominance between the affected traits. We show that conditions for balancing selection under AP expand under the likely scenario that the strength of selection on each fitness component differs between the sexes. Our model also predicts that the vast majority of balanced polymorphisms have sexually antagonistic effects on total fitness, despite the absence of sexual antagonism for individual fitness components. We conclude that AP polymorphisms are less difficult to maintain than predicted by prior theory, even under our conservative assumption that selection on components of fitness is universally sexually concordant. We discuss implications for the maintenance of genetic variation, and for inferences of sexual antagonism that are based on sex-specific phenotypic selection estimates – many of which are based on single fitness components.
Data from: Pleiotropy in the wild: the dormancy gene DOG1 exerts cascading control on life-cycles
In the wild, organismal life cycles occur within seasonal cycles, so shifts in the timing of developmental transitions can alter the seasonal environment experienced subsequently. Effects of genes that control the timing of prior developmental events can therefore be magnified in the wild because they determine seasonal conditions experienced by subsequent life stages, which can influence subsequent phenotypic expression. We examined such environmentally-induced pleiotropy of developmental-timing genes in a field experiment with Arabidopsis thaliana. When studied in the field under natural seasonal variation, an A. thaliana seed-dormancy gene, Delay Of Germination 1 (DOG1), was found to influence not only germination, but also flowering time, overall life history, and fitness. Flowering time of the previous generation, in turn, imposed maternal effects that altered germination, the effects of DOG1 alleles, and the direction of natural selection on these alleles. Thus under natural conditions, germination genes act as flowering genes and potentially vice versa. These results illustrate how seasonal environmental variation can alter pleiotropic effects of developmental-timing genes, such that effects of genes that regulate prior life stages ramify to influence subsequent life stages. In this case, one gene acting at the seed stage impacted the entire life cycle.
Data from: The fitness effects of a pale mutant in the aposematic seed bug Lygaeus simulans indicate pleiotropy between warning coloration and life history
Conspicuous warning colours that signal chemical or other defences are common in the natural world. For instance, such aposematic warning patterns of red-and-black or yellow-and-black are common among insect taxa, particularly in the order Hemiptera, often forming the basis of Batesian and/or Müllerian mimicry rings. In addition, it has been repeatedly noted that colour polymorphisms or mutants that influence pigmentation can show pleiotropy with other behavioural, physiological or life-history traits. Here we describe a pale mutant of the seed bug Lygaeus simulans that appeared in our lab population in 2012, which differs in colour to the wild-type bugs. Through multigenerational experimental crosses between wild-type and pale mutant L. simulans, we first show that the pale phenotype segregates as a single Mendelian locus, with the pale allele being recessive to the wild-type. Next, we show (1) that there is a large heterozygous advantage in terms of fecundity, (2) that pale females suffer reduced longevity, and (3) that pale males have increased body length compared to wild-type homozygotes. Our data therefore suggest that the colour locus is pleiotropic with a number of life-history traits, opening the door for a more complete genetic analysis of aposematic colouration in this species. In addition, this phenotype will be useful as a visible genetic marker, providing a tool for investigating sperm competition and other post-copulatory drivers of sexual selection in this species.
Data from: Environmental pleiotropy and population demography direct adaptation under antibiotic selection
Evolutionary rescue following environmental change requires mutations permitting population growth in the new environment. If change is severe enough to prevent most of the population reproducing, rescue becomes reliant on mutations already present. If change is sustained, the fitness effects in both environments, and how they are associated---termed `environmental pleiotropy'---may determine which alleles are ultimately favoured. A population's demographic history---its size over time---influences the variation present. Although demographic history is known to affect the probability of evolutionary rescue, how it interacts with environmental pleiotropy during severe and sustained environmental change remains unexplored. Here, we demonstrate how these factors interact during antibiotic resistance evolution, a key example of evolutionary rescue fuelled by pre-existing mutations with pleiotropic fitness effects. We combine published data with novel simulations to characterise environmental pleiotropy and its effects on resistance evolution under different demographic histories. Comparisons among resistance alleles typically revealed no correlation for fitness---i.e. neutral pleiotropy---above and below the sensitive strain's minimum inhibitory concentration. Resistance allele frequency following experimental evolution showed opposing correlations with their fitness effects in the presence and absence of antibiotic. Simulations demonstrated that effects of environmental pleiotropy on allele frequencies depended on demographic history. At the population level, the major influence of environmental pleiotropy was on mean fitness, rather than the probability of evolutionary rescue or diversity. Our work suggests that determining both environmental pleiotropy and demographic history is critical for predicting resistance evolution, and we discuss the practicalities of this during in vivo evolution.
Data from: Role of pleiotropy during adaptation of TEM-1 β-lactamase to two novel antibiotics
Pleiotropy is a key feature of the genotype–phenotype map, and its form and extent have many evolutionary implications, including for the dynamics of adaptation and the evolution of specialization. Similarly, pleiotropic effects of antibiotic resistance mutations may affect the evolution of antibiotic resistance in the simultaneous or fluctuating presence of different antibiotics. Here, we study the role of pleiotropy during the in vitro adaptation of the enzyme TEM-1 β-lactamase to two novel antibiotics, cefotaxime (CTX) and ceftazidime (CAZ). We subject replicate lines for four rounds of evolution to selection with CTX and CAZ alone, and in their combined and fluctuating presence. Evolved alleles show positive correlated responses when selecting with single antibiotics. Nevertheless, pleiotropic constraints are apparent from the effects of single mutations and from selected alleles showing smaller correlated than direct responses and smaller responses after simultaneous and fluctuating selection with both than with single antibiotics. We speculate that these constraints result from structural changes in the oxyanion pocket surrounding the active site, where accommodation of CTX and the larger CAZ is balanced against their positioning with respect to the active site. Our findings suggest limited benefits from the combined or fluctuating application of these related cephalosporins for containing antibiotic resistance.
Data from: Environmentally induced changes in correlated responses to selection reveal variable pleiotropy across a complex genetic network
Selection in novel environments can lead to a coordinated evolutionary response across a suite of characters. Environmental conditions can also potentially induce changes in the genetic architecture of complex traits, which in turn could alter the pattern of the multivariate response to selection. We describe a factorial selection experiment using the nematode Caenorhabditis remanei in which two different stress-related phenotypes (heat and oxidative stress resistance) were selected under three different environmental conditions. The pattern of covariation in the evolutionary response between phenotypes or across environments differed depending on the environment in which selection occurred, including asymmetrical responses to selection in some cases. These results indicate that variation in pleiotropy across the stress response network is highly sensitive to the external environment. Our findings highlight the complexity of the interaction between genes and environment that influences the ability of organisms to acclimate to novel environments. They also make clear the need to identify the underlying genetic basis of genetic correlations in order understand how patterns of pleiotropy are distributed across complex genetic networks.
Interaction between mutation type and gene pleiotropy drives parallel evolution in the laboratory
<p><span>What causes evolution to be repeatable is a fundamental question in evolutionary biology. Pleiotropy, i.e. the effect of an allele on multiple traits, is thought to enhance repeatability by constraining the number of available beneficial mutations. Additionally, pleiotropy may promote repeatability by allowing large fitness benefits of single mutations via adaptive combinations of phenotypic effects. Yet, this latter evolutionary potential may be reaped solely by specific types of mutations able to realize optimal combinations of phenotypic effects while avoiding the costs of pleiotropy. Here, we address the interaction of gene pleiotropy and mutation type on evolutionary repeatability in a meta-analysis of experimental evolution studies with <em>Escherichia coli</em>. We hypothesize that single-nucleotide polymorphisms are principally able to yield large fitness benefits by targeting highly pleiotropic genes, whereas indels and structural variants provide smaller benefits and are restricted to genes with lower pleiotropy. By using gene connectivity as proxy for pleiotropy, we show that nondisruptive single-nucleotide polymorphisms (SNPs) in highly pleiotropic genes yield the largest fitness benefits, since they contribute more to parallel evolution, especially in large populations, than inactivating SNPs, indels and structural variants. Our findings underscore the importance of considering genetic architecture together with mutation type for understanding evolutionary repeatability.</span></p>
Data from: Adaptation via pleiotropy and linkage: association mapping reveals a complex genetic architecture within the stickleback Eda locus
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Data from: What affects the predictability of evolutionary constraints using a G-matrix? The relative effects of modular pleiotropy and mutational correlation
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Data from: Ecological speciation in sympatric palms: 1. Gene expression, selection and pleiotropy
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Data from: The fitness effects of a pale mutant in the aposematic seed bug Lygaeus simulans indicate pleiotropy between warning coloration and life history
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Data from: The basis of antagonistic pleiotropy in hfq mutations that have opposite effects on fitness at slow and fast growth rates
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Data from: Pleiotropy in the melanocortin system: expression levels of this system are associated with melanogenesis and pigmentation in the tawny owl (Strix aluco)
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Data from: Hormonal pleiotropy and the evolution of allocation trade-offs
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Interaction between mutation type and gene pleiotropy drives parallel evolution in the laboratory
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