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Biology subjects

Pelletier, K.

Publications and source records attributed to Pelletier, K..

5 recordsLinked to original sources

Polygenic architecture of adaptation to a high-altitude environment for Drosophila melanogaster wing shape and size.

As is typical of small insects, populations of Drosophila melanogaster adapted to high altitude environments evolved increased body size, disproportionality large wings, and differing wing shape compared to low-altitude ancestors. In one instance the colonization of high-altitude environments in Ethiopia is recent (2000-3000 years ago), and is a useful system to study alleles contributing to adaptive divergence. Unlike predictions derived from formulations Fisher-Kimura-Orr geometric model based on de novo mutations concurrent with selection, recent models predict segregating alleles in a population are more likely to contribute to adaptation on short time scales, particularly when populations are large and genetically diverse, like D. melanogaster. Strains derived from lowland ([~]500m above sea level - ASL) and highland ([~]3000m ASL) populations were used to generate F20 advanced-intercrosses. From each cross, phenotypically extreme individuals for size and shape were pool-sequenced, and genetic differentiation among pools of individuals demonstrated a polygenic architecture of divergence for size and shape. We identified one QTL of large effect, contributing to adaptive divergence in shape. This QTL is not observed in all crosses, pointing to the importance of examining independent genetic backgrounds when mapping alleles contributing to adaptation. Despite the intrinsic links between shape and size, we find a unique genetic basis of adaptation for these traits. This work demonstrates that many alleles, throughout the genome, rather than single, large effect alleles, contribute to adaption for Drosophila wing shape and size, adding to the growing body of evidence for polygenic adaptation.

evolutionary biology↗

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↗

Cardiac function and ECM morphology are altered with high fat diets in Drosophila

Cardiovascular disease is characterized by aberrant and excessive extracellular matrix (ECM) remodelling, termed fibrosis. Fibrotic remodelling is typically triggered by inflammation, which occurs systemically in obesity. Despite the contribution of fibrosis to adverse clinical outcomes and disease progression, there are no available treatments for this condition. Developing therapeutics for chronic conditions requires an understanding of in vivo ECM regulation, and how the ECM responds to a systemic challenge. We have therefore developed a Drosophila model for obesity via chronic high fat diet feeding and evaluated the response of the cardiac ECM to this metabolic challenge. We found that this model displays a striking disorganization of the cardiac ECM, with corresponding deficits in heart function. Our study shows that different genotypes tolerate varying levels of high fat diets, and that some genotypes may require a different percentage of fat supplementation for achieving an optimal obesity phenotype.

molecular biology↗

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↗

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↗