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Genotype by random environmental interactions gives an advantage to non-favored minor alleles.

ABSTRACT: Fixation probability, the probability that the frequency of a newly arising mutation in a population will eventually reach unity, is a fundamental quantity in evolutionary genetics. Here we use a number of models (several versions of the Moran model and the haploid Wright-Fisher model) to examine fixation probabilities for a constant size population where the fitness is a random function of both allelic state and spatial position, despite neither allele being favored on average. The concept of fitness varying with respect to both genotype and environment is important in models of cancer initiation and progression, bacterial dynamics, and drug resistance. Under our model spatial heterogeneity redefines the notion of neutrality for a newly arising mutation, as such mutations fix at a higher rate than that predicted under neutrality. The increased fixation probability appears to be due to rare alleles having an advantage. The magnitude of this effect can be large, and is an increasing function of the spatial variance and skew in fitness. The effect is largest when the fitness values of the mutants and wild types are anti-correlated across environments. We discuss results for both a spatial ring geometry of cells (such as that of a colonic crypt), a 2D lattice and a mass-action (complete graph) arrangement.

SUBMITTER: Mahdipour-Shirayeh A

PROVIDER: S-EPMC5507875 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Genotype by random environmental interactions gives an advantage to non-favored minor alleles.

Mahdipour-Shirayeh A A Darooneh A H AH Long A D AD Komarova N L NL Kohandel M M

Scientific reports 20170712 1

Fixation probability, the probability that the frequency of a newly arising mutation in a population will eventually reach unity, is a fundamental quantity in evolutionary genetics. Here we use a number of models (several versions of the Moran model and the haploid Wright-Fisher model) to examine fixation probabilities for a constant size population where the fitness is a random function of both allelic state and spatial position, despite neither allele being favored on average. The concept of f ...[more]

PMID: 28701726

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Project description:BACKGROUND:Genome-wide association studies (GWASs) have revealed relationships between over 57,000 genetic variants and diseases. However, unlike Mendelian diseases, complex diseases arise from the interplay of multiple genetic and environmental factors. Natural selection has led to a high tendency of risk alleles to be enriched in minor alleles in Mendelian diseases. Therefore, an allele that was previously advantageous or neutral may later become harmful, making it a risk allele. METHODS:Using data in the NHGRI-EBI Catalog and the VARIMED database, we investigated whether (1) GWASs more easily detect risk alleles and (2) facilitate evolutionary insights by comparing risk allele frequencies of different diseases. We conducted computer simulations of P-values for association tests when major and minor alleles were risk alleles. We compared the expected proportion of SNVs whose risk alleles were minor alleles with the observed proportion. RESULTS:Our statistical results revealed that risk alleles were enriched in minor alleles, especially for variants with low minor allele frequencies (MAFs <?0.1). Our computer simulations revealed that >?50% risk alleles were minor alleles because of the larger difference in the power of GWASs to differentiate between minor and major alleles, especially with low MAFs or when the number of controls exceeds the number of cases. However, the observed ratios between minor and major alleles in low MAFs (<?0.1) were much larger than the expected ratios of GWAS's power imbalance, especially for diseases whose average risk allele frequencies were low, such as myopia, sudden cardiac arrest, and systemic lupus erythematosus. CONCLUSIONS:Minor alleles are more likely to be risk alleles in the published GWASs on complex diseases. One reason is that minor alleles are more easily detected as risk alleles in GWASs. Even when correcting for the GWAS's power imbalance, minor alleles are more likely to be risk alleles, especially in some diseases whose average risk allele frequencies are low. These analyses serve as a starting point for future studies on quantifying the degree of negative natural selection in various complex diseases.

Project description:As global climates change, alien species are anticipated to have a growing advantage relative to their indigenous counterparts, mediated through consistent trait differences between the groups. These insights have largely been developed based on interspecific comparisons using multiple species examined from different locations. Whether such consistent physiological trait differences are present within assemblages is not well understood, especially for animals. Yet, it is at the assemblage level that interactions play out. Here, we examine whether physiological trait differences observed at the interspecific level are also applicable to assemblages. We focus on the Collembola, an important component of the soil fauna characterized by invasions globally, and five traits related to fitness: critical thermal maximum, minimum and range, desiccation resistance and egg development rate. We test the predictions that the alien component of a local assemblage has greater basal physiological tolerances or higher rates, and more pronounced phenotypic plasticity than the indigenous component. Basal critical thermal maximum, thermal tolerance range, desiccation resistance, optimum temperature for egg development, the rate of development at that optimum and the upper temperature limiting egg hatching success are all significantly higher, on average, for the alien than the indigenous components of the assemblage. Outcomes for critical thermal minimum are variable. No significant differences in phenotypic plasticity exist between the alien and indigenous components of the assemblage. These results are consistent with previous interspecific studies investigating basal thermal tolerance limits and development rates and their phenotypic plasticity, in arthropods, but are inconsistent with results from previous work on desiccation resistance. Thus, for the Collembola, the anticipated advantage of alien over indigenous species under warming and drying is likely to be manifest in local assemblages, globally.

Project description:Changes in the coral reef complex can affect predator-prey relationships, resource availability and niche utilisation in the associated fish community, which may be reflected in decreased stability of the functional traits present in a community. This is because particular traits may be favoured by a changing environment, or by habitat degradation. Furthermore, other traits can be selected against because degradation can relax the association between fishes and benthic habitat. We characterised six important ecological traits for fish species occurring at seven sites across a disturbed coral reef archipelago in Indonesia, where reefs have been exposed to eutrophication and destructive fishing practices for decades. Functional diversity was assessed using two complementary indices (FRic and RaoQ) and correlated to important environmental factors (live coral cover and rugosity, representing local reef health, and distance from shore, representing a cross-shelf environmental gradient). Indices were examined for both a change in their mean, as well as temporal (short-term; hours) and spatial (cross-shelf) variability, to assess whether fish-habitat association became relaxed along with habitat degradation. Furthermore, variability in individual traits was examined to identify the traits that are most affected by habitat change. Increases in the general reef health indicators, live coral cover and rugosity (correlated with distance from the mainland), were associated with decreases in the variability of functional diversity and with community-level changes in the abundance of several traits (notably home range size, maximum length, microalgae, detritus and small invertebrate feeding and reproductive turnover). A decrease in coral cover increased variability of RaoQ while rugosity and distance both inversely affected variability of FRic; however, averages for these indices did not reveal patterns associated with the environment. These results suggest that increased degradation of coral reefs is associated with increased variability in fish community functional composition resulting from selective impacts on specific traits, thereby affecting the functional response of these communities to increasing perturbations.

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Genotype by random environmental interactions gives an advantage to non-favored minor alleles.

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Genotype by random environmental interactions gives an advantage to non-favored minor alleles.

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