Examining Rates of Evolution Within the Drosophila Insulin Signaling Pathway

We are interested in understanding the evolutionary rates of genes that function in a biological network. We focused on the insulin signaling pathway due to its conservation across the animal kingdom, with literature documenting many interactions within this pathway. We used synteny and sequence similarity to identify orthologs of Drosophila melanogaster genes in a variety of Drosophilaspecies. Our focus included genes seen as central to the pathway such as Pdk1 and Tor as well as other genes such as HDAC4and srlwith at least one known connection to insulin signaling. In collaboration with the Genomics Education Partnership, we performed manual gene annotations to derive accurate protein coding sequences within our species of interest. We took a comparative genomics approach using BLAST and data from the UCSC Genome Browser, including RNA-seq, additional alignment algorithms, and gene predictors to inform identification of exon-intron boundaries. Comparison of the determined protein coding sequences from the target Drosophila species to the established sequences from D. melanogasterprovides insight into how a gene has been evolving since these two species diverged. Initial analysis suggests large variability in the rates of evolution taking place in our genes of interest and some correlation between higher expression level and greater sequence conservation. We are also considering our data with respect to a gene's position within its network and its role in biological pathways to help illuminate which factors dictate gene evolution rate. We hope our methodology and results can add to our understanding of gene evolution across biological systems. © FASEB.