Joshua B. Plotkin

Assistant Professor of Biology (SAS), Computer and Information Science
(SEAS)
Ph.D., Princeton University

Research

OVERVIEW
I use mathematics and computation to study questions in evolutionary biology. My research is primarily concerned with the origin and maintenance of genetic variation within populations. Related interests include the evolution of robustness and adaptability, the evolutionary ecology of viral populations,somatic evolution, and the evolution of social norms.

EVOLUTIONARY POPULATION GENETICS
We are broadly interested in population-genetic theory. A primary goal is the development of statistical methods for inferring the action of natural selection from intra-specific polymorphism data and from inter-specific sequence variation. Of particular interest are methods to infer the distribution of selection pressures across sites, the recombination rates between sites, and the structure of epistatic interactions among sites.

ROBUSTNESS AND ADAPTABILITY
How do organisms ensure robustness against genetic and environmental perturbations? How do organsisms simultaneously achieve sufficient plasticity to adapt to changing environments?

These questions are particularly puzzling in the context of viral populations. Viruses are bound by the same constraints that shape the evolution of higher organisms: the need to replicate with fidelity and adapt to local environments. Viral proteins are governed by the same physical laws that determine folding and functionality in higher organisms. But viruses are often subject to genetic mutations and environmental changes at rates that vastly exceed those of all other living organisms. As a result, the persistence of viruses presents an enigma: How can a viral population achieve both sufficient robustness against high mutation rates, as well as sufficient plasticity to adapt to rapidly changing environments? On the one hand, a viral population must purge itself of deleterious mutants; but at the same time it must be prepared to leverage genetic diversity in order to escape a host's immune system.

We are exploring the counterpoised requirements for robustness and adaptability by developing mathematical models of viral evolution. Models are complemented and parameterized by statistical inferences from empirical sequence data.

VIRAL MOLECULAR EVOLUTION
Influenza viruses offer an extraordinary opportunity for improving our understanding of molecular evolution. Roughly 30% of sites in influenza's primary surface antigen have undergone amino-acid substitutions over the past four decades –- the equivalent of millions of years of protein evolution in mammals. Influenza's remarkable evolutionary rate is driven by selection for novel antigenic variants that evade antibodies in the host population. We are leveraging the vast quantity of available viral sequence data to quantify the nature of selection pressures on influenza proteins. We are particularly interested in the differences between diversifying and directional positive selection, temporal changes in selective regimes, the identification of selectively neutral networks, and the structure of epistatic relations between sites.

Related projects include the modeling and inference of influenza epidemic fluctuations.

TROPICAL SPECIES DIVERSITY
We also pursue research into the distribution and abundances of tropical tree species. To what degree can we predict species diversity within a regional community? How does spatial autocorrelation affect our ability to estimate local diversity and species turnover from restricted samples? We address these questions through simulation, modelling, and analysis of largescale tropical forest surveys.