Molecular Mechanisms of Adaptive Evolution in Pathogen Populations

University Of Maryland, College Park, College Park MD

Investigators

Abstract

This research will address a central question in pathogen biology about which we know little: what types of changes in what types of genes account for the emergence of host specificity? The entomopathogenic fungus Metarhizium anisopliae provides an excellent model system for studying this question. It is a radiating species, and contains both generalist and specialized lineages with broad and narrow host ranges. Strains representing evolutionary distances ranging from <1 to11 million years can be selected and their natural molecular variation allows analysis of processes of both adaptive change and phylectic differentiation still in operation, even in intermediate states. To investigate how regulatory variation and changes in gene content contribute to infection characteristics, cDNA or DNA from generalist and specialist strains will be co-hybridized to thousands of ESTs expressed during infection processes by a reference strain. This will: 1) investigate the contribution to pathogenic specialization of gene duplication, divergence and degradation, and 2) identify pseudogenes that will provide a unique dataset to study the role of neutral sequence evolution in a fungus and its underlying mutational processes in different lineages. Using atlases of gene expression, combined with technologies to modulate mRNA levels, the investigator will explore the extent to which control of gene expression is used as a vehicle by evolution to define the host range of multiple strains. In further experiments he will look at the role of regulatory genes, including several that may play a role in host switching. In terms of broad impact, genetic variation is a powerful tool to study the molecular basis of adaptation (one of the "Holy Grails" of evolutionary biology) and the questions being asked here on the mechanisms by which novel pathogens emerge address many basic, yet poorly understood issues that span much of molecular evolution. Addressing these issues will greatly increase our knowledge of the mechanisms by which new pathogens emerge with either wide or narrow host ranges. It will also greatly increase our knowledge of the dynamics of a fungal genome and help define the appropriate evolutionary distances for answering questions on mutation rates, gene degradation and modulation of gene expression. This will help establish a foundation for comparative genomics and inform optimal choices for broader sampling of fungal genomes. The project will also provide research opportunities for a postdoctoral fellow, graduate students and undergraduate students from underrepresented groups.