Abstract
In order to understand how oxidative stress signal transduction pathways evolve, we analyzed the molecular evolution of the p38 MAPK (p38K) gene family across the genus Drosophila. p38K family genes play a vital role in oxidative stress resistance and are also important for organismal development and immunity. We find that the p38Ka and p38Kb genes are highly conserved across the genus and that p38Kc is more recently evolved. We further find that the p38Kb genomic locus includes conserved binding sites for the AP-1 and lola-PT transcription factors. Accordingly, over-expression of either AP-1 or lola-PT in D. melanogaster is sufficient to induce transcription of p38Kb under normal conditions, while under oxidative stress only lola-PT over-expression was able to induce p38Kb transcription. In addition, exposure to oxidative stress results in increased p38K protein levels in a number of species. These increased levels are associated with an increased resistance to oxidative stress across species. We also find that the presence of a lola-PT binding site in the p38Kb locus is predictive of the species’ survival in response to oxidative stress. Through this comparative genomics analysis, we have identified biologically relevant transcription factor binding sites that regulate the expression of p38Kb and are associated with resistance to oxidative stress.