Biology subjects

Williams-Simon, P. A.

Publications and source records attributed to Williams-Simon, P. A..

4 recordsLinked to original sources

bioRxiv2025

Multiple methods for assessing learning and memory in Drosophila melanogaster demonstrates the highly complex, context-dependent genetic underpinnings of cognitive traits

Learning and memory are fundamental for an individual to be able to respond to changing stimuli in their environment. Between individuals we see variation in their ability to perform learning and memory tasks, however, it is still largely unknown what genetic factors may impact this variability. To gain better insight to the genetic components impacting variation in learning and memory, we use recombinant inbred lines (RILs) from the Drosophila synthetic population resource (DSPR), a multiparent mapping population exhibiting natural variation in many traits. Using a reward based associative learning and memory assay, we trained flies to associate an odor with a sucrose reward under starvation condition and measured olfactory learning and memory ability in y-mazes for 50 DSPR RILs. While we do not find significant QTLs for olfactory learning or memory, we found suggestive regions that may be contributing to variability in performance when trained to different odors. We provide evidence that performance with specific odors should be considered different phenotypes and introduce new methods for analysis for olfactory y-maze assays with multiple decision points. Additionally, we compare our data to previously collected place learning and memory data to show there is limited correlation in performance outcomes.

genetics↗

bioRxiv2023

Naturally segregating genetic variants contribute to thermal tolerance in a D. melanogaster model system.

Thermal tolerance is a fundamental physiological complex trait for survival in many species. For example, everyday tasks such as foraging, finding a mate, and avoiding predation, are highly dependent on how well an organism can tolerate extreme temperatures. Understanding the general architecture of the natural variants of the genes that control this trait is of high importance if we want to better comprehend how this trait evolves in natural populations. Here, we take a multipronged approach to further dissect the genetic architecture that controls thermal tolerance in natural populations using the Drosophila Synthetic Population Resource (DSPR) as a model system. First, we used quantitative genetics and Quantitative Trait Loci (QTL) mapping to identify major effect regions within the genome that influences thermal tolerance, then integrated RNA-sequencing to identify differences in gene expression, and lastly, we used the RNAi system to 1) alter tissue-specific gene expression and 2) functionally validate our findings. This powerful integration of approaches not only allows for the identification of the genetic basis of thermal tolerance but also the physiology of thermal tolerance in a natural population, which ultimately elucidates thermal tolerance through a fitness-associated lens.

evolutionary biology↗

bioRxiv2019

Diverse biological processes coordinate the transcriptional response to nutritional changes in a Drosophila melanogaster multiparent population

BackgroundEnvironmental variation in the amount of resources available to populations challenge individuals to optimize the allocation of those resources to key fitness functions. This coordination of resource allocation relative to resource availability is commonly attributed to key nutrient sensing gene pathways in laboratory model organisms, chiefly the insulin/TOR signaling pathway. However, the genetic basis of diet-induced variation in gene expression is less clear.\n\nResultsTo describe the natural genetic variation underlying nutrient-dependent differences, we used an outbred panel derived from a multiparental population, the Drosophila Synthetic Population Resource. We analyzed RNA sequence data from multiple female tissue samples dissected from flies reared in three nutritional conditions: high sugar (HS), dietary restriction (DR), and control (C) diets. A large proportion of genes in the experiment (19.6% or 2,471 genes) were significantly differentially expressed for the effect of diet, 7.8% (978 genes) for the effect of the interaction between diet and tissue type (LRT, Padj. < 0.05). Interestingly, we observed similar patterns of gene expression relative to the C diet, in the DR and HS treated flies, a response likely reflecting diet component ratios. Hierarchical clustering identified 21 robust gene modules showing intra-modularly similar patterns of expression across diets, all of which were highly significant for diet or diet-tissue interaction effects (false discovery rate, FDR Padj. < 0.05). Gene set enrichment analysis for different diet-tissue combinations revealed a diverse set of pathways and gene ontology (GO) terms (two-sample t-test, FDR < 0.05). GO analysis on individual co-expressed modules likewise showed a large number of terms encompassing a large number of cellular and nuclear processes (Fisher exact test, Padj. < 0.01). Although a handful of genes in the IIS/TOR pathway including Ilp5, Rheb, and Sirt2 showed significant elevation in expression, known key genes such as InR, chico, insulin peptide genes, and the nutrient-sensing pathways were not observed.\n\nConclusionsOur results suggest that a more diverse network of pathways and gene networks mediate the diet response in our population. These results have important implications for future studies focusing on diet responses in natural populations.

genomics↗

bioRxiv2019

Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

Learning and memory are critical functions for all animals, giving individuals the ability to respond to changes in their environment. Within populations, individuals vary, however the mechanisms underlying this variation in performance are largely unknown. Thus, it remains to be determined what genetic factors cause an individual to have high learning ability, and what factors determine how well an individual will remember what they have learned. To genetically dissect learning and memory performance, we used the DSPR, a multiparent mapping resource in the model system Drosophila melanogaster, consisting of a large set of recombinant inbred lines (RILs) that naturally vary in these and other traits. Fruit flies can be trained in a \"heat box\" to learn to remain on one side of a chamber (place learning), and can remember this (place memory) over short timescales. Using this paradigm, we measured place learning and memory for [~]49,000 individual flies from over 700 DSPR RILs. We identified 16 different loci across the genome that significantly affect place learning and/or memory performance, with 5 of these loci affecting both traits. To identify transcriptomic differences associated with performance, we performed RNA-Seq on pooled samples of 7 high performing and 7 low performing RILs for both learning and memory and identified hundreds of genes with differences in expression in the two sets. Integrating our transcriptomic results with the mapping results allowed us to identify nine promising candidate genes, advancing our understanding of the genetic basis underlying natural variation in learning and memory performance.

genetics↗