Research
We use host-pathogen interactions as models for studying mechanisms of evolution.
Research Areas of Focus
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Pathogen-driven evolution
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Arms races
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Mimicry
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Experimental evolution
Pathogen-driven Evolution
The histogram above groups genes by dN/dS, the ratio of rates of non-synonymous (dN) and synonymous (dS) codon changes in comparisons between human, chimp, and rhesus. Immunity genes locked in molecular arms races can evolve rapidly under extreme positive selection; dN/dS >2.
Host-pathogen interactions are battlefronts for influence over host functions. From an evolutionary perspective, each interaction can bear heavily on the fitness of both hosts and pathogens. Therefore, these interactions drive some of the most rapid evolution found in nature and can provide basic insights into the evolutionary process.
We study the consequences of pathogen-driven evolution on cells and host immunity factors. Protein surfaces at these interfaces often evolve in a manner resembling molecular arms races. We are also interested in cases where pathogens use molecular mimicry to gain advantages against hosts.
In addition, we use experimental evolution to determine the evolutionary potential of viruses and understand the rules by which they adapt.
“Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!”
―Lewis Carroll, Alice Through the Looking Glass
Arms Races
Protein surfaces at host-pathogen interfaces often evolve in ways that resemble arms races. This phenomenon of genetic conflict has been described by the Red Queen hypothesis, which posits that antagonistic entities vie for dominance in seesawing battles of ongoing adaptations. Molecular arms races often play out repeatedly at the same interfaces and leave behind some of the strongest signals of natural selection in the genome. These arms races can be discerned using phylogenetic analysis, which can provide novel insights for studying the dynamics of host-pathogen interactions.
Mimicry
A swallowtail butterfly next to the crystal structure of a virus encoded mimic of a kinase substrate
We are interested in cases where pathogens use mimicry to disrupt host processes. Mimicry is observed widely in nature (e.g. Batesian mimicry among butterfly species). However, little is known about how molecular mimcry impacts host-pathogen interactions. Pathogens use the strategy of mimicry to interfere with immunity and co-opt a wide variety of host processes to their advantage. This poses a conundrum for hosts to maintain critical activities while not being exploited by pathogenic mimics honed to divert host functions. What then are the evolutionary prospects for hosts to counteract mimics?
Experimental Evolution
While experiments based on phylogenetic reconstructions provide a powerful means of retrospectively studying host-pathogen interactions, experimental evolution offers a prospective view of virus evolution where potential adaptations can be monitored in real-time. Recent advances in deep seequencing coupled with recombinant tools make it possible to quickly determine the genetic basis of a variety of adaptations.
We are using experimental evolution to address open questions related to virus evolution, such as mechanisms of rapid evolution and the trade-offs between host range and virulence.