Conservation of Ilp4, Pdk1 and HDAC4 Across Drosophila Species

Abstract

The degree of gene conservation is influenced by many factors including relative expression levels and number of interactions of the gene and its protein product. In collaboration with the Genomics Education Project, the conservation of several insulin signaling pathway genes and their protein products within Drosophila has been investigated. Insulin‐like peptide 4 (Ilp4) functions in the insulin signaling pathway by binding to the insulin receptor, thus triggering the phosphatidylinositol 3‐kinase pathway, which involves Phosphoinositide‐dependent kinase 1 (Pdk1). Another player in the insulin‐signaling pathway investigated in this work is Histone deacetylase 4 (HDAC4), which catalyzes the removal of acetyl functional groups from histone proteins, ultimately decreasing the expression of associated genes. Predicting the relative conservation of these genes is not trivial. For example, Ilp4 is at the beginning of the pathway and has one contact according to the Flybase physical interaction network. This might indicate the potential for greater evolutionary change over time, but contradicting this hypothesis is this insulin‐like peptide’s importance as a ligand in the pathway. Pdk1 also shows one contact on Flybase, but is located towards the beginning of the pathway, suggesting a relatively higher evolutionary rate. HDAC4 plays a role in many other cellular processes and so should be well conserved. To evaluate conservation, we first used BLAST to identify orthologs of these three genes across several Drosophilaspecies. We then evaluated conservation in terms of amino acid identity, exon length, number of exons, and degree of synteny using genomic sequences, BLAST, and evidence such as gene prediction tracks and RNA expression data available on the UCSC Genome Browser. Thus far, Pdk1 has demonstrated the greatest similarity over multiple species, with less conservation being observed in Ilp4 and HDAC4. This suggests the complexity in determining the interplay between number of protein contacts and pathway position on evolutionary rate.