OVERVIEW
We use mathematics and computation to study questions in evolutionary biology and ecology. Research in the group is concerned primarily 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, stochastic population dynamics, and the evolution of social norms.
EVOLUTIONARY POPULATION GENETICS
We are broadly interested in molecular evolution and 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 rate amoung sites, and the structure of epistatic interactions among sites.
ROBUSTNESS AND ADAPTABILITY
How do organisms ensure robustness against genetic and environmental perturbations? How do organisms 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 inference techniques applied to empirical sequence data.
VIRAL 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.
SPECIES DIVERSITY
We also pursue research on the distribution and abundances of species, and their history of diversification. To what degree can we predict species diversity within a regional community? How does spatial autocorrelation influence our estimates of local diversity and species turnover from restricted samples? How can we infer the history of species diversity in a taxonomic group from extant molecular sequences? We address these questions through simulation, modelling, and analysis of field data.
CURRENT
ALUMNI
RECENT VISITORS RECENT COLLABORATORS
Joshua Plotkin is the principal investigator. [CV]
Jeremy Draghi completed his PhD in Biology at Yale, on the evolution of evolvability.
Alex Stewart completed his PhD in biological complexity at University College London, on
the evolution of transcriptional networks.
Jakub Otwinowski completed his PhD in Physics at Emory, using
statistical physics to model adaptation.
David Bostick completed his PhD in Physics at UNC, on molecular dynamics simulations of biomembranes.
Premal Shah completed his PhD in Biology at UT Knoxville, on
the molecular evolution of codon bias.
Mitchell Johnson is a graduate student in Biology. He completed his
Masters in Biomathematics at UCLA.
Etienne Rajon completed his PhD in Biology at the
University of Lyon, on the evolution of life-history
strategies in variable environments.
Ricky Der completed his PhD in Mathematics at Penn, on generalized
Markov models in population genetics.
David McCandlish completed his PhD in Biology at Duke, on evolutionary
dynamics under weak mutation.
Yang Ding is a graduate student in Biology. He completed his MS in Biology at Boston College and BS in mathematics at Wuhan
University.
Grzegorz Kudla is now a senior scientist in the MRC Human Genetics Group,
at the University of Edinburgh.
Helene Morlon is now a permanent scientist of the CNRS, at Ecole Polytechniqe in Paris.
Michael Levy is now a tenure-track Assistant Professor in the Biostatistics Department at the University of Pennsylvania.
Todd Parsons is now a a permanent scientist of the CNRS, at UPMC-Paris VI.
Sergey Kryazhimskiy now a research fellow at Harvard University.
Alison Feder is in Oxford for a year, in advance of graduate school at
Stanford.
Serena Rezny received her Master's in Applied Math at Penn,
and is now a PhD student in Statistics at Univeristy of Chicago.
Anchal Vishnoi is now a lecturer at JNU, Delhi.
Sebastian Akle is now a graduate student in Organismal and Evolutionary Biology at Harvard.
Gasper Tkacik is now a tenure-track assistant professor at the Institute of Science and Technology, Austria.
Etienne Rajon will start as a tenure-track Assistant Professor at
University of Lyon, September 2013.
Daril Vilhena is currently a graduate student at the University of Washington, in Biology.
POSTDOCS
Requirements for the position include: a proven record of self-motivated research; a PhD in mathematics, statistics, physics, biology or related area; excellent quantitative skills. The ideal candidate should be familiar with scientific programming.
The postdoctoral fellowships provides a competitive annual stipend plus benefits and health insurance. Start date and term are negotiable. Highly motivated applicants, of any nationality, are encouraged to email a statement of research interests, CV, and contact details for three references to jplotkin (at) sas.upenn.edu. Informal inquiries are also welcomed.
GRADUATE STUDENTS
UNDERGRADUATE STUDENTS
Contact
Dr. Joshua B. Plotkin
Penn Department of Biology
219 Lynch Labs
433 S. University Ave
Philadelphia, PA 19104
jplotkin (at) sas.upenn.edu
PUBLICATIONS
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We gratefully acknowledge funding from:
- U.S. National Institute of General Medical Sciences (NIGMS)
- U.S. National Institute of Allergy and Infectious Diseases (NIAID)
- U.S. Defense Advanced Research Projects Agency (DARPA)
- U.S. Army Research Office
- U.S. Department of the Interior
- Alfred P. Sloan Foundation
- Burroughs Wellcome Fund
- James S. McDonnell Foundation
- National Academies Keck Futures Initiative
- United Nations Development Program
- David & Lucile Packard Foundation
- National Philanthropic Trust