PgmNr P2038: Genome-wide Analysis of Starvation-selected Drosophila melanogaster- a Genetic Model of Obesity.

Authors:
Christopher Hardy 1 ; Molly Burke 2 ; Mira Han 1 ; Logan Everett 3 ; Kathryn Lantz 1 ; Allen Gibbs 1


Institutes
1) University of Nevada Las Vegas, Las Vegas, NV; 2) Oregon State University, Corvallis, OR; 3) North Carolina State State University, Raleigh, NC.


Abstract:

Experimental evolution affords the opportunity to investigate adaptation to stressful environments. Combining experimental evolution with recent developments in whole-genome sequencing has elevated the field by providing insight into the dynamics of evolution as well as a new tool to discriminate genes involved in polygenic traits. Here, we performed an “Evolve and Resequence” (E&R) study where we selected for starvation-resistance in populations of Drosophila melanogaster for over 80 generations. In response to selection, the starvation-selected lines have developed an obese condition, storing nearly twice the level of fats than their unselected controls. While the excess fats provide a ~3-fold increase in survival time upon starvation, the imbalance in lipid homeostasis incurs evolutionary cost. Some of these tradeoffs resemble obesity-associated pathologies in mammals including metabolic depression, low activity levels, dilated cardiomyopathy and disrupted sleeping patterns. To determine the genetic basis of these traits we sequenced genomic DNA from the selected lines and their controls. We found 1,046,373 polymorphic sites, many of which diverged between selection treatments. In addition, we found a wide range of genetic heterogeneity between the replicates of the selected lines, suggesting multiple mechanisms of adaptation. Genome-wide levels of heterozygosity in the selected lines were low, with many large blocks of SNPs nearing fixation. To find loci under selection, we generated a new algorithm to control for the effects of genetic drift. We mapped these loci to a set of 1,453 genes, which were enriched for genes related to morphogenesis, development, tissue differentiation and regulation of metabolism. The results of our study speak to the evolutionary origins of obesity and provide new targets to understand the polygenic nature of obesity in a unique model system.