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Pleiotropy or linkage? Their relative contributions to the genetic correlation of quantitative traits and detection by multitrait GWA studies
Full text linkGenetic correlations between traits may cause correlated responses to selection. Previous models described the conditions under which genetic correlations are expected to be maintained. Selection, mutation, and migration are all proposed to affect genetic correlations, regardless of whether the underlying genetic architecture consists of pleiotropic or tightly linked loci affecting the traits. Here, we investigate the conditions under which pleiotropy and linkage have different effects on the genetic correlations between traits by explicitly modeling multiple genetic architectures to look at the effects of selection strength, degree of correlational selection, mutation rate, mutational variance, recombination rate, and migration rate. We show that at mutation-selection(-migration) balance, mutation rates differentially affect the equilibrium levels of genetic correlation when architectures are composed of pairs of physically linked loci compared to architectures of pleiotropic loci. Even when there is perfect linkage (no recombination within pairs of linked loci), a lower genetic correlation is maintained than with pleiotropy, with a lower mutation rate leading to a larger decrease. These results imply that the detection of causal loci in multitrait association studies will be affected by the type of underlying architectures, whereby pleiotropic variants are more likely to be underlying multiple detected associations. We also confirm that tighter linkage between nonpleiotropic causal loci maintains higher genetic correlations at the traits and leads to a greater proportion of false positives in association analyses.Peer reviewe
The relative impact of evolving pleiotropy and mutational correlation on trait divergence
Full text linkBoth pleiotropic connectivity and mutational correlations can restrict the decoupling of traits under divergent selection, but it is unknown which is more important in trait evolution. To address this question, we create a model that permits within-population variation in both pleiotropic connectivity and mutational correlation, and compare their relative importance to trait evolution. Specifically, we developed an individual-based stochastic model where mutations can affect whether a locus affects a trait and the extent of mutational correlations in a population. We find that traits can decouple whether there is evolution in pleiotropic connectivity or mutational correlation, but when both can evolve, then evolution in pleiotropic connectivity is more likely to allow for decoupling to occur. The most common genotype found in this case is characterized by having one locus that maintains connectivity to all traits and another that loses connectivity to the traits under stabilizing selection (subfunctionalization). This genotype is favored because it allows the subfunctionalized locus to accumulate greater effect size alleles, contributing to increasingly divergent trait values in the traits under divergent selection without changing the trait values of the other traits (genetic modularization). These results provide evidence that partial subfunctionalization of pleiotropic loci may be a common mechanism of trait decoupling under regimes of corridor selection.Peer reviewe
Pleiotropy or linkage? Their relative contributions to the genetic correlation of quantitative traits and detection by multi-trait GWA studies.
No full text<p>Data for "Pleiotropy or linkage? Their relative contributions to the genetic correlation of quantitative traits and detection by multi-trait GWA studies". Results from simulations with four different genetic architectures to compare how pleiotropy and linkage differentially affect the genetic correlation between traits. Three different sets of genetic architecture had varying distances between 120 pairs of additive loci affecting two quantitative traits. Each pair of loci was located on its own chromosome (i.e., unlinked to other pairs) and the recombination distance between each pair on a chromosome was either 0cM, 0.1cM, or 1cM apart for a particular genetic architecture representing no recombination between linked loci, as well as an average and an extreme value of recombination at ``hotspots'' in the human genome, respectively. A fourth genetic architecture consisted of 120 unlinked, additive, pleiotropic loci that affected both quantitative traits. Each simulation was run with 5,000 initially monomorphic (variation is gradually introduced through mutations), diploid individuals for 10,000 generations achieving mutation-selection(-migration) balance in order to observe general patterns of genetic correlation in the near-absence of drift. Individuals were hermaphrodites mating at random within a population, with non-overlapping generations. Phenotypes were calculated for each of the two traits modeled by summing the allelic values of all loci affecting one trait. Gaussian stabilizing selection was applied and determined the survival probability of juveniles. To examine the effects of the strength of stabilizing selection on each trait and strength of correlational selection between traits, different sets of simulations were run with selection strength of 50 or 100 and correlational selection of 0.5 and 0.9. To examine the effects of mutational input on genetic correlation between traits, different sets of simulations were run with mutation rates of 0.001, 0.0001, or 0.00001, and mutational effect sizes of 0.1, 0.01, or 0.001. </p>
<p>To examine the effects of migration from a source population on genetic correlation between traits, additional sets of simulations were run with uni-directional migration from a second population (as in an island-mainland model with each population consisting of 5000 individuals) with backward migration rates of 0.1, 0.01, and 0.001. The backward migration rate represents the average proportion of new individuals in the focal population whose parent is from the source population. The local optimum values for the two traits in the source population were set at 10 units distance from the focal population's local optimum. Both focal and source populations had weak stabilizing selection with a strength of 100, the focal population had no correlational selection between the two traits and the source population had a correlational selection of 0 or 0.9. Fifty replicate simulations were run for each set of parameter values and statistics were averaged over replicates.</p>
Domestication syndrome via indirect selection in simulated cereal grains
Full text linkDomestication syndrome in cereal grains is commonly thought to be the product of domestication through a combination of direct artificial selection and indirect natural selection by humans. We propose an agent-based model of grain domestication. We simulate cereal grains with four genes that impact their reproductive cycle undergoing harvesting and selective planting by simulated humans. When direct artificial selection is applied to one gene domestication syndrome emerges in the other genes as a result of indirect natural selection. In the absence of direct artificial selection no domestication syndrome emerged, consistent with periods of predomestication cultivation in human history. Domesticated variants are strongest when humans select for traits inconsistent with the wild type traits, and weakest when humans select for traits consistent with the wild type
StabilizingSelectionNemoInitFiles
No full textInit files for running with Nemo v2.3.4 (with variable modularity). For 10,000 generations of stabilizing selection to reach mutation-selection balance. G-matrix eigen decomposition and evolutionary metric analyses performed on 10,000th generation for each simulation averaged over 50 replicates
DirectionalSelectionNemo_Init_Files
No full textInit files for running with Nemo v2.3.4 (with variable modularity). For 2,000 generations of directional selection performed on 10,000th generation of Stabilizing Selection population simulation output. Number of generations to a fitness cut-off for each simulation averaged over 50 replicates
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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