Endosymbiosis, parasitism, and genome evolution

Microorganisms thrive in virtually every habitat imaginable. Understanding how they adapt to changing environments is a fundamental problem in biomedical research. The genetic makeup of endosymbionts -- cells that live inside other cells -- often differs significantly from free-living organisms, and while endosymbiosis can be an important first step in the evolution of an intracellular parasite, little is known about the molecular processes underlying this transition. We propose to use advanced molecular and cell biological techniques, ultra-modern DNA sequencing, and computational methods to improve our understanding of how the genomes of single-celled, nucleus-containing organisms change in response to intracellular life. Specific questions to be addressed include examining how non-essential DNA is removed from an endosymbionts genome, and determining how (and how often) genes move from an endosymbionts genome to that of the host cell in which it resides. We will study the genomes of recently established endosymbionts as well as those more anciently evolved in order to gain perspective from both ends of the continuum between transient endosymbiont and permanent intracellular resident. Although fundamental in nature, the research we propose has a number of practical benefits. The endosymbionts we will study live inside single-celled amoebae that are animal pathogens, and so understanding the genetic interactions between the endosymbiont and its host will aid in the development of anti-parasitic agents. These organisms are also related to important human disease-causing parasites; determining their genetic blueprint will improve our knowledge of how the causative agents of Chagas disease and African sleeping sickness first evolved and the genes they share with their endosymbiotic, but non-pathogenic, relatives.