Senior Scholar Award in Global Infectious Disease
John C. Boothroyd, Ph.D.
Stanford University School of Medicine

Evolution of Virulence in Eukaryotic Pathogens

The role of sex in spread of a disease is usually thought of in terms of sexually transmitted diseases and sex between an infected host and an uninfected sexual partner. But sex between the pathogens themselves also plays a crucial role in how a given disease emerges and evolves. Such evolution can give rise to pathogens able to infect a wider variety of cells in a greater number of host species or to increase their ability to be transmitted. The combination of these factors can result in dramatic and rapid changes in the virulence of a pathogen species.

We are using the protozoan parasite, Toxoplasma gondii, as a model for studying the role of sex in the evolution of virulence in eukaryotic parasites. T. gondii is one of the most “successful” parasites on earth, at least in terms of warm-blooded animals: it is found world-wide, in a vast number of warm-blooded animal species and at high prevalence (e.g., 10-80% of humans, depending on the region). It can reproduce limitlessly through asexual reproduction or it can undergo classic sexual reproduction. This unusual choice gives the species both the ability to experiment with new gene combinations following sexual recombination as well as the opportunity to asexually expand any given progeny that happened on just the right genetic make-up to great numbers. As a result, it appears that a few genetically identical, clonal lines of this parasite have come to dominate in many parts of the world.

Our goal is to further understand how the combination of sexual and asexual reproduction have impacted the evolution of this parasite, especially in terms of its disease-causing properties in humans and other animals. We will be comparing the progeny of a sexual cross to determine how quickly new strains can arise, what genes influence the virulence and how large a role this process plays in the evolution of this parasite in nature. The results should have broad significance for our understanding of other eukaryotic pathogens that rely on sexual exchange for their evolution.

Contact Dr. Boothroyd.