Evolution of the phosphate starvation response in Ascomycota yeast
 

My laboratory is interested in how complexity arises from an ancestral signal transduction pathway and what selective pressures tailor a pathway for growth in diverse niches. We investigate the phosphate signal transduction (PHO) pathway in the Ascomycota fungal lineage with the goal of discovering alternative signaling pathway architectures. Understanding the diversity of networks which give rise to the phosphate starvation response will allow for a better understanding of how genome changes (i.e. whole genome duplication, gene duplication and loss, and point mutations) alter pathway complexity and will help to explain the evolutionary steps required to tailor a pathway for growth in diverse niches.

Ascomycetes diverged from a common fungal ancestor over 100 million years ago and aspects of the PHO pathway from Saccharomyces cerevisiae (brewer's yeast) are conserved in the lineage, providing a rare opportunity to address these questions. Many comparative biology approaches identify patterns in protein sequence and infer a function, but understanding the evolution of network architecture requires molecular genetic and functional genomic experiments to test inferences and hypotheses. The ascomycetes in our studies can be cultivated in standard medium and are amenable to existing molecular genetic techniques. Currently, we have two main goals in our research:

1. Define the phosphate starvation response and PHO pathway in Candida glabrata

C. glabrata and S. cerevisiae last shared a common ancestor between 10 and 100 million years ago. By characterizing the PHO pathway in a yeast closely related to S. cerevisiae but inhabiting a different ecological niche, the properties of the pathway that are conserved and/or dispensable are being identified. Our preliminary data indicate that there are significant differences in the PHO pathway between the two organisms, which may affect the ability of the two species to thrive in different types of phosphate environments. 1. We are focusing on the regulation Pho4 – the phosphate starvation-regulated transcription factor. 2. We are determining which traits are ancestral by examining ascomycetes that shared a common ancestor with S. cerevisiae and C. glabrata prior to whole genome duplication. 3. We are examining how modified PHO pathway architectures allow for different niche exploitation.

2. Define the PHO pathway in Schizosaccharomyces pombe

The archaeascomycete, Sz. pombe, is highly diverged from S. cerevisiae, and it is unknown how Sz. pombe regulates a transcriptional response to phosphate starvation. We are screening and characterizing mutants that are defective in the regulation of the phosphate-regulated gene PHO1, with a primary focus of attempting to identify a phosphate-regulated transcription factor in Sz. pombe. This work will provide context for how a divergent organism in a similar niche has evolved a phosphate-starvation response

Why do we care about these studies?

We expect these studies to shed light on the evolutionary steps required for a pathway to alter its specificity, possibly to uncover novel antifungal targets, and to provide clues as to how all cells respond to changes in environmental conditions.