This is the research for which we are writing an NSF grant on. The overall goal of this project is to characterize the evolution of the oxidative stress resistance trait and the transcriptional response across the budding yeast phylogeny, with a particular focus on the comparison between related pathogenic species and their low pathogenic-potential relatives.
The rationale of the work is that oxidative stress is experienced by all aerobic organisms, but the types of ROS, their strength and frequencies vary across environments. The budding yeast in the Sacchromycetes class provides a great system for studying the evolution of oxidative stress resistance and response, because these species occupy a diverse set of environments. In particular, there are multiple yeast pathogens in this group, which are subjected to oxidative bursts from the host immune system. Empirical studies suggest that these species have a higher oxidative stress resistance than related non-pathogenic species. What makes this system particularly attractive is that based on their phylogenetic relationship, it is believed that pathogenecity arose multiple times, providing multiple instances of adaptation to the host and allowing us to identify both convergent and distinct solutions to common challenges.
Overall approach: In this work we set out to formally test the above hypothesis using a carefully selected group of yeasts, which include two subgroups of pathogens with their low pathogenic-potential relatives. In addition to characterizing the evolution of the resistance phenotype, we will profile the transcriptional response dynamics in a core set of species to identify the mechanisms behind the phenotypic divergence.
The significance of this work is twofold. First, determining the relationship between stress resistance and pathogenecity will shed light on the factors critical for the rise of fungal pathogens, which is predicted to happen at a higher rate due to the effect of global warming (allowing more species to be pre-adapted to the higher body temperature of mammals). Revealing the transcriptional changes behind the phenotypic evolution will help us understand the genetic basis for stress adaptation, and could help us identify new strategies to weaken their defense and enhance the host immune system. Second, our work will shed light on the general properties of stress response evolution, including the repeatability of genomic evolution (whether a limited number of solutions or many different ones were realized) and how the stress response networks were rewired during evolution to achieve a new phenotypic state that is adapted to the novel environment.