Biology subjects

Dworkin, I.

Publications and source records attributed to Dworkin, I..

14 recordsLinked to original sources

bioRxiv2026

Condition manipulation reveals an increase in sex-specific additive genetic variance, and reduced intersex genetic covariances in Drosophila prolongata, a species with sexual trait exaggeration

The between sex genetic correlation for traits has long been hypothesized as a constraint to the evolution of sexual dimorphism. Both empirical and theoretical work has suggested that this constraint is influenced by genotype-sex-environment interactions. We examine genotype-sex-environment interactions in both sexually exaggerated and non-exaggerated legs of Drosophila prolongata, to examine the role of organismal condition on evolvability of an extreme trait. We employed a nested full-sib half-sib crossing design, providing food either ad libitum, or restricting food during larval growth, to each brood. When provided food ad libitum, inter-sex genetic correlations between traits is high and positive, whereas under food restriction this correlation substantially weakens, with a modest negative sign. Similarly, comparisons of the G matrix across sexes becomes less associated under food restriction. We discuss these results in the context of the growing appreciation of the factors that facilitate sex-specific evolutionary change.

evolutionary biology↗

bioRxiv2025

Genetic architecture of the developing forelegs of Drosophila prolongata; an exaggerated weapon and ornament

Extreme secondary sexual traits are some of the most striking phenotypes in nature. Studies on the genetics of these phenotypes have largely focused on within-species functional analyses of signalling pathways. Although useful, these do not provide insight into the evolutionary mechanisms that occur during the evolution of trait exaggeration. Drosophila prolongata offers an exceptional opportunity to explore the evolution of trait exaggeration, as it is the only species in the melanogaster species group with male-specific foreleg size exaggeration under both intra- and intersexual selection. Here, we used sex-specific RNA-seq from fore- and midleg tissues during early development and after initiation of sexually dimorphic growth between these tissues in D. prolongata. We also sampled the same developmental stages in D. carrolli ([~]4MYA divergence) and D. melanogaster ([~]20MYA). Using comparisons of gene expression between sexes, species, tissues, and developmental stages, we found a positive relationship between the number, but not the magnitude of differential expression of sex-biased genes, with the extent of phenotypic dimorphism. One gene with a large effect, grain, caused D. prolongata-like leg size phenotypes in D. melanogaster legs when knocked down. We further found only modest changes to magnitude and direction of expression differences in signalling pathways previously implicated in sexually dimorphic evolution. This suggests that these pathways regulating trait expression and dimorphism but may not be primary drivers of their phenotypic evolution. Significance statementHow sexes evolve distinct forms while developing from a shared genome continues to be incompletely resolved. We explore a sexually dimorphic exaggerated trait, enlarged forelegs in Drosophila prolongata, and compare changes in sex-biased gene expression between tissues and developmental stages in D. prolongata and two closely related species without foreleg exaggeration. We show that major developmental pathways dont appear to change substantially in their direction or magnitude of expression between species. We further show a transcription factor, grain, that when knocked-down, induces D. prolongata leg-like phenotypes in D. melanogaster at low penetrance. Our results suggest that despite large morphological differences and patterns of dimorphism, gene expression changes between the developing tissues may be more modest than previously thought.

evolutionary biology↗

bioRxiv2024

The role of resource defensibility in facilitating sexually-selected weapon evolution: An experimental evolution test

Animal weapons have evolved multiple times primarily for battling for access to mates. Despite intra-sexual selection being common, weapon evolution has evolved relatively rarely. So why do weapons not evolve more commonly? It has been hypothesized that three precursors are necessary for the initiation of weapon evolution: high variance in reproductive success, patchy high-value resources, and spatial environments conducive to one-on-one competition. Here, we test this hypothesis by performing experimental evolution in Drosophila melanogaster, utilizing heterogeneous environments where conditions facilitating territorial defense and opportunities for competitive interactions vary. We examine changes in sexually dimorphic morphology and male aggression that are predicted to occur, based on this model. We also examine whether condition dependence for sexual dimorphism has evolved after 35 and 75 generations of experimental evolution. Aggression did increase, albeit modestly, in environments that facilitate resource defense. Morphological changes are modest although with some trait specific changes to allometry, generally in the opposite direction of our predictions. Condition dependence trends in the opposite direction from those predicted by our hypothesis as well. We discuss our results in the context of the necessary conditions for the evolution of weapons, and if, and when condition dependence of trait exaggeration may evolve.

evolutionary biology↗

bioRxiv2023

Sexually discordant selection is associated with trait specific morphological changes and a complex genomic response

Sexes often have differing fitness optima, potentially generating intra-locus sexual conflict, as each sex bears a genetic load of alleles beneficial to the other sex. One strategy to evaluate conflict in the genome is to artificially select populations discordantly, against established sexual dimorphism, reintroducing attenuated conflict. We investigate a long-term artificial selection experiment reversing sexual size dimorphism in Drosophila melanogaster during [~]350 generations of sexually discordant selection. We explore morphological and genomic changes to identify loci under selection between the sexes in discordantly and concordantly size selected treatments. Despite substantial changes to overall size, concordant selection maintained ancestral sexual dimorphism. However, discordant selection altered size dimorphism in a trait-specific manner. We observe multiple, possible soft selective sweeps in the genome, with size related genes showing signs of selection. Patterns of genomic differentiation between the sexes within lineages identified potential sites maintained by sexual conflict. One discordant selection lineage shows a pattern of elevated genomic differentiation on chromosome 3L, consistent with the maintenance of sexual conflict. Our results suggest measurable signs of conflict and differentially segregating alleles between the sexes due to discordant selection.

evolutionary biology↗

bioRxiv2022

Complexities of recapitulating polygenic effects in natural populations: replication of genetic effects on wing shape in artificially selected and wild caught populations of Drosophila melanogaster.

Identifying the genetic architecture of complex traits is important to many geneticists, including those interested in human disease, plant and animal breeding, and evolutionary genetics. Advances in sequencing technology and statistical methods for genome-wide association studies (GWAS) have allowed for the identification of more variants with smaller effect sizes, however, many of these identified polymorphisms fail to be replicated in subsequent studies. In addition to sampling variation, this failure to replicate reflects the complexities introduced by factors including environmental variation, genetic background, and differences in allele frequencies among populations. Using Drosophila melanogaster wing shape, we ask if we can replicate allelic effects of polymorphisms first identified in a GWAS (Pitchers et al. 2019) in three genes: dachsous (ds), extra-macrochaete (emc) and neuralized (neur), using artificial selection in the lab, and bulk segregant mapping in natural populations. We demonstrate that multivariate wing shape changes associated with these genes are aligned with major axes of phenotypic and genetic variation in natural populations. Following seven generations of artificial selection along the ds shape change vector, we observe genetic differentiation of variants in ds and genomic regions containing other genes in the hippo signaling pathway. This suggests a shared direction of effects within a developmental network. We also performed artificial selection with the emc shape change vector, which is not a part of the hippo signaling network, but showed a largely shared direction of effects. The response to selection along the emc vector was similar to that of ds, suggesting that the available genetic diversity of a population, summarized by the genetic (co)variance matrix (G), influenced alleles captured by selection. Despite the success with artificial selection, bulk segregant analysis using natural populations did not detect these same variants, likely due to the contribution of environmental variation and low minor allele frequencies, coupled with small effect sizes of the contributing variants.

genetics↗

bioRxiv2022

Reexamining Waddington: Canalization and new mutations are not required for the evolution of genetic assimilation

Over 65 years ago, Waddington demonstrated ancestrally phenotypically plastic traits can evolve to become constitutive, a process he termed genetic assimilation. Genetic assimilation evolves rapidly, assumed to be in large part due to segregating genetic variation only expressed in rare/novel environments, but otherwise phenotypically cryptic. Despite previous work suggesting a substantial role of cryptic genetic variation contributing to the evolution of genetic assimilation, some have argued for a prominent role for new mutations of large effect concurrent with selection. Interestingly, Waddington was less concerned by the relative contribution of CGV or new variants, but aimed to test the role of canalization, an evolved form of robustness. While canalization has been extensively studied, its role in the evolution of genetic assimilation is disputed, in part because explicit tests of evolved robustness are lacking. To address these questions, we recreated Waddingtons selection experiments on an environmentally sensitive change in Drosophila wing morphology (crossvein development), using many independently evolved replicate lineages. Using these, we show that 1) a polygenic CGV, but not new variants of large effect are largely responsible for the evolved response demonstrated using both genomic and genetic approaches. 2) Using both environmental manipulations and mutagenesis of the evolved lineages that there is no evidence for evolved changes in canalization contributing to genetic assimilation. Finally, we demonstrate that 3) CGV has potentially pleiotropic and fitness consequences in natural populations and may not be entirely "cryptic".

evolutionary biology↗

bioRxiv2021

The influence of adaptation to life at high-altitude on condition dependent sexual shape and size dimorphism in Drosophila melanogaster

Sexual dimorphism is common despite factors such as inter-sex genetic correlations and sex-specific patterns of selection that might limit its evolution. Sexual dimorphism can be phenotypically plastic and condition dependent, that themselves may be targets of selection. However, it remains unclear how sexual dimorphism, its plasticity and condition dependence evolves, in particular during rapid adaptation to a new environment. Furthermore, the interplay between SSD and other forms of dimorphism, such as shape dimorphism co-evolves. Using Sub-Saharan populations of Drosophila melanogaster that vary for size and shape as a result of adaptation to high altitude environments, we examined sex specific patterns of developmental plasticity. We raised strains of Drosophila from low (Zambia) and high (Ethiopia) altitude populations varying for food quality or rearing temperature. We observed expected differences in wing size and shape due to population, sex and plasticity. While larval mass showed substantial evolved changes for sex specific condition dependence, effects on wing size and shape were modest. We examined shape-size allometric effects between groups. Allometric effects were generally similar across sexes, but differed substantially due to population of origin and plasticity. We discuss findings within the context of the evolution of plasticity for SSD, condition dependence and allometric relationships.

evolutionary biology↗

bioRxiv2020

Spatial heterogeneity in resources alters selective dynamics in Drosophila melanogaster

Environmental features can alter the behaviours and phenotypes of organisms and populations evolving within them including the dynamics between natural and sexual selection. Experimental environmental manipulation, particularly when conducted in experiments where the dynamics of the purging of deleterious alleles are compared, has demonstrated both direct and indirect effects on the strength and direction of selection. However, many of these experiments are conducted with fairly simplistic environments when it is not always clear how or why particular forms of spatial heterogeneity may influence behaviour or selection. Using Drosophila melanogaster, we tested three different spatial environments designed to determine if spatial constraint of critical resources influences the efficiency of natural and sexual selection. We conducted two allele purging experiments to 1) assess the effects of these spatial treatments on the selective dynamics of six recessive mutations, and 2) determine how these dynamics changed when sexual selection was relaxed and the spatial area was reduced. We found that allele purging dynamics depended on spatial environment, however the patterns of purging rates between the environments differed across distinct deleterious mutations. We also found that for two of the mutations, the addition of sexual selection increased the purging rate.

evolutionary biology↗

bioRxiv2019

Genetic and environmental canalization are not associated among altitudinally varying populations of Drosophila melanogaster

Organisms are exposed to environmental and mutational effects influencing both mean and variance of phenotypes. Potentially deleterious effects arising from this variation can be reduced by the evolution of buffering (canalizing) mechanisms, ultimately reducing phenotypic variability. As such, there has been interest regarding the plausible conditions that enable canalizing mechanisms to evolve. Under some models, the circumstances under which genetic canalization evolves is limited, despite apparent empirical evidence for it. It has been argued that canalizing mechanisms for mutational effects may evolve as a correlated response to environmental canalization (the congruence model). Yet, empirical evidence has not consistently supported the prediction of a correlation between genetic and environmental canalization. In a recent study, a population of Drosophila melanogaster adapted to high altitude showed evidence of genetic decanalization relative to those from low-altitudes. Using strains derived from these populations, we tested if they also varied for environmental canalization, rearing them at different temperatures. Using wing morphology, we quantified size, shape, cell (trichome) density and frequencies of mutational defects. We observed the expected differences in wing size and shape, cell density and mutational defects between the high- and low-altitude populations. However, we observed little evidence for a relationship between a number of measures of environmental canalization with population or with visible defect frequency. Our results do not support the predicted association between genetic and environmental canalization.

evolutionary biology↗

bioRxiv2019

Sexual selection does not increase the rate of compensatory adaptation to a mutation influencing a secondary sexual trait in Drosophila melanogaster

Theoretical work predicts that sexual selection can enhance natural selection, increasing the rate of adaptation to new environments and helping purge harmful mutations. While some experiments support these predictions, remarkably little work has addressed the role of sexual selection on compensatory adaptation--populations ability to compensate for the costs of deleterious alleles that are already present. We tested whether sexual selection, as well as the degree of standing genetic variation, affect the rate of compensatory evolution via phenotypic suppression in experimental populations of Drosophila melanogaster. These populations were fixed for a spontaneous mutation causing mild abnormalities in the male sex comb, a structure important for mating success. We fine-mapped this mutation to an [~]85 kb region on the X chromosome containing three candidate genes, showed that the mutation is deleterious, and that its phenotypic expression and penetrance vary by genetic background. We then performed experimental evolution, including a treatment where opportunity for mate choice was limited by experimentally enforced monogamy. Although evolved populations did show some phenotypic suppression of the morphological abnormalities in the sex comb, the amount of suppression did not depend on the opportunity for sexual selection. Sexual selection, therefore, may not always enhance natural selection; instead, the interaction between these two forces may depend on additional factors.

evolutionary biology↗

bioRxiv2018

The Sheep and the Goats: Distinguishing transcriptional enhancers in a complex chromatin landscape

Predicting regulatory function of non-coding DNA using genomic information remains a major goal in genomics, and an important step in interpreting the cis-regulatory code. Regulatory capacity can be partially inferred from transcription factor occupancy, histone modifications, motif enrichment, and evolutionary conservation. However, combinations of these features in well-studied systems such as Drosophila have limited predictive accuracy. Here we examine the current limits of computational enhancer prediction by applying machine-learning methods to an extensive set of genomic features, validating predictions with the Fly Enhancer Resource, which characterized the transcriptional activity of approximately fifteen percent of the genome. Supervised machine learning trained on a range of genomic features identify active elements with a high degree of accuracy, but are less successful at distinguishing tissue-specific expression patterns. Consistent with previous observations of their widespread genomic interactions, many transcription factors were associated with enhancers not known to be direct functional targets. Interestingly, no single factor was necessary for enhancer identification, although binding by the 'pioneer' transcription factor Zelda was the most predictive feature for enhancer activity. Using an increasing number of predictive features improved classification with diminishing returns. Thus, additional single-timepoint ChIP data may have only marginal utility for discerning true regulatory regions. On the other hand, spatially- and temporally-differentiated genomic features may provide more power for this type of computational enhancer identification. Inclusion of new types of information distinct from current chromatin-immunoprecipitation data may enable more precise identification of enhancers, and further insight into the features that distinguish their biological functions.

genomics↗

bioRxiv2017

Compensatory evolution via cryptic genetic variation: Distinct trajectories to phenotypic and fitness recovery

Populations are constantly exposed to deleterious alleles, most of which are purged via natural selection. However, deleterious fitness effects of alleles can also be suppressed by compensatory adaptation. Compensatory mutations can act directly to reduce deleterious effects of an allele. Alternatively, compensation may also occur by altering other aspects of an organisms phenotype or performance, without suppressing the phenotypic effects of the deleterious allele. Moreover, the origin of allelic variation contributing to compensatory adaptation remains poorly understood. Compensatory evolution driven by mutations that arise during the selective process are well studied. However less is known about the role standing (cryptic) genetic variation plays in compensatory adaptation. To address these questions, we examined evolutionary trajectories of natural populations of Drosophila melanogaster fixed for mutations that disrupt wing morphology, resulting in deleterious effects on several components of fitness. Lineages subjected only to natural selection, evolved modifications to courtship behavior and several life history traits without compensation in wing morphology. Yet, we observed rapid phenotypic compensation of wing morphology under artificial selection, consistent with segregating variation for compensatory alleles. We show that alleles contributing to compensation of wing morphology have deleterious effects on other fitness components. These results demonstrate the potential for multiple independent avenues for rapid compensatory adaptation from standing genetic variation, which ultimately may reveal novel adaptive trajectories.

evolutionary biology↗

bioRxiv2017

How Well Do You Know Your Mutation? Complex Effects Of Genetic Background On Expressivity, Complementation, And Ordering Of Allelic Effects

For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and variation across alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development) of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis.

genetics↗

bioRxiv2017

The power of a multivariate approach to genome-wide association studies: an example with Drosophila melanogaster wing shape

Due to the complexity of genotype-phenotype relationships, simultaneous analyses of genomic associations with multiple traits will be more powerful and more informative than a series of univariate analyses. In most cases, however, studies of genotype-phenotype relationships have analyzed only one trait at a time, even as the rapid advances in molecular tools have expanded our view of the genotype to include whole genomes. Here, we report the results of a fully integrated multivariate genome-wide association analysis of the shape of the Drosophila melanogaster wing in the Drosophila Genetic Reference Panel. Genotypic effects on wing shape were highly correlated between two different labs. We found 2,396 significant SNPs using a 5% FDR cutoff in the multivariate analyses, but just 4 significant SNPs in univariate analyses of scores on the first 20 principal component axes. A key advantage of multivariate analysis is that the direction of the estimated phenotypic effect is much more informative than a univariate one. Exploiting this feature, we show that the directions of effects were on average replicable in an unrelated panel of inbred lines. Effects of knockdowns of genes implicated in the initial screen were on average more similar than expected under a null model. Association studies that take a phenomic approach in considering many traits simultaneously are an important complement to the power of genomics. Multivariate analyses of such data are more powerful, more informative, and allow the unbiased study of pleiotropy.

genetics↗