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 Adaptation
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.
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.
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.
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.
Davorka Gulisija will complete her PhD in Zoology at the University of Wisconsin (December 2013), on adaptation to dynamic environments.
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.
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 École Normale Supérieure.
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 Université Pierre et Marie Curie.
Sergey Kryazhimskiy now a research fellow at Harvard University and a Burroughs Wellcome Fund CASI awardee.
Alison Feder is now a graduate student in Biology at Stanford.
Etienne Rajon is now a tenure-track Assistant Professor at University of Lyon.
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.
Serena Rezny received her Master's in Applied Math at Penn, and is now a PhD student in Statistics at Univeristy of Chicago.
Daril Vilhena recently received his PhD in Biology from the University of Washington.
Lena Gieschen, David Krakauer, Macarena Toll-Riera.
Charlie Epstein, Michael Desai, Sridhar Hannenhalli, Jonathan Dushoff, Mark Lipsitch, David Krakauer
Several postdoctoral fellowships (2-3 years) are available in the mathematical biology group of Dr. Joshua B. Plotkin at the University of Pennsylvania. The specific research project is flexible and can be tailored to the interests of the individual, but it will fall under the broad purview of evolutionary and ecological theory. Areas of interest in the Plotkin lab include theoretical population genetics, the evolutionary ecology of viral populations, the evolution of robustness and adaptability, and the evolution of social norms.
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.
Students interested in graduate study in evolutionary and ecological theory are encouraged to contact Dr. Plotkin. Students may matriculate through one of several Penn graduate groups: Biology Department, Genomics & Computational Biology, Computer Science, or Applied Mathematics. Please email your CV to Dr. Plotkin, along with a cover letter explaining why you want to join the group.
Students with a quantitative background and an interest in evolution or
ecology are encouraged to contact Dr. Plotkin regarding the possibility
of term or summer projects. Send an email
explaining what you hope to get out of research
with our lab, along with CV, to jplotkin (at) sas.upenn.edu.
ContactDr. Joshua B. Plotkin
Penn Department of Biology
219 Lynch Labs
433 S. University Ave
Philadelphia, PA 19104
jplotkin (at) sas.upenn.edu
- Feder A, Kryazhimskiy S, Plotkin JB. Identifying signatures of
selection in genetic time series. Genetics (in
- Draghi J, Plotkin JB.
Selection biases the prevalence and type of epistasis along adaptive
Evolution 67: 3120–3131 (2013) [pdf]
- Stewart A, Plotkin JB.
From extortion to generosity, evolution in the Iterated Prisoner's
PNAS 110: 15348-15353 (2013) [pdf]
- Lipsitch M, Fisman D, Plotkin JB, Simonsen L.
Ferret H7N9 flu model questioned.
Nature 501: 33 (2013) [pdf]
- Shah P, Ding Y, Niemczyk M, Kudla G, Plotkin JB.
Rate-limiting steps in yeast protein translation.
Cell 153: 1589-1601 (2013)
- McCandlish D, Rajon E, Shah P, Ding Y, Plotkin JB.
The role of epistasis in protein evolution.
Nature 497: E1-E2 (2013) [pdf]
- Rajon E, Plotkin JB.
The evolution of genetic architectures underlying quantitative traits.
Proceedings of The Royal Society B 280: 20131552 (2013)
- Stewart A, Plotkin JB.
The evolution of complex gene regulation by low-specificity binding
sites. Proceedings of The Royal Society B 280:
20131313 (2013) [pdf]
- Li Y, Bostick D, Sullivan C, Myers J, Griesemer S, St. George K,
Plotkin JB, Hensley S.
Single Hemagglutinin mutations that alter both antigenicity and
Journal of Virology 87: 9904-9910 (2103) [pdf]
- Li Y, Myers J, Bostick D, et al.
Immune history shapes specificity of pandemic H1N1 Influenza antibody responses. Journal of Experimental Medicine 210: 1493-1500 (2013) [pdf]
- Harrison RD, Tan S, Plotkin JB, Slik F, Detto M, Brenes T, Itoh A, Davis SJ. Consequences of defaunation for a tropical tree community. Ecology Letters 16: 687–694 (2013) [pdf]
- Stewart A, Seymour R, Pomiankowski A, Plotkin JB. The population genetics of cooperative gene regulation. BMC Evolutionary Biology 12: 173 (2012) [pdf]
- Stewart A, Hannenhalli S, Plotkin JB. Why transcription factor binding sites are ten nucleotides long. Genetics 192: 973-985 (2012) [pdf]
- Ding Y, Shah P, Plotkin JB. Weak 5' mRNA structure in short eukaryotic genes. Genome Biology and Evolution 4: 1046-1053 (2012) [pdf]
- Der R, Epstein C, Plotkin JB. The dynamics of neutral and selected alleles when the offspring distribution is skewed. Genetics 191: 1331-1344 (2012) [pdf]
- Morlon H, Kemps B, Plotkin JB, Brisson D. Explosive radiation of a bacterial species group. Evolution 66: 2577-2586 (2012) [pdf]
- Lipsitch M, Plotkin JB, Simonsen L, Bloom B. Evolution, safety, and highly pathogenic Influenza viruses. Science 336: 1529-1531 (2012) [pdf]
- Stewart A, Plotkin JB. Extortion and cooperation in the Prisoner's Dilemma. PNAS 109: 10134-10135 (2012) [pdf]
- Stewart A, Parsons T, Plotkin JB. Environmental robustness and the adaptability of populations. Evolution 66: 1598-1612 (2012) [pdf]
- Toll-Riera M, Bostick D, Alba M, Plotkin JB. Structure and age jointly influence rates of protein evolution. PLoS Computational Biology 8:1002542 (2012) [pdf]
- Walczak AM, Nicolaisen LE, Plotkin JB, Desai MM. The structure of genealogies in the presence of purifying selection: a fitness-class coalescent. Genetics 190: 753-779 (2012) [pdf]
- Desai MM, Nicolaisen LE, Walczak AM, Plotkin JB. The structure of allelic diversity in the presence of purifying selection. Theoretical Population Biology 8: 144-157 (2012) [pdf]
- Draghi J, Plotkin JB. A network of paths toward innovation. Bioessays 34: 518–520 (2012) [pdf]
- Morlon H, Parsons T, Plotkin JB. Reconciling molecular phylogenies with the fossil record. PNAS 108: 16327-16332 (2011) [pdf] [cover]
- Der R, Epstein C, Plotkin JB. Generalized population models and the nature of genetic drift. Theoretical Population Biology 80: 80-99 (2011) [pdf]
- Vishnoi A, Sethupathy P, Simola D, Plotkin JB, Hannenhalli S. Genome-wide survey of natural selection on functional, structural, and network properties of polymorphic sites in Saccharomyces paradoxus. Molecular Biology and Evolution 28: 2615-2627 (2011) [pdf]
- Levy M, Small D, Vilhena D, Bowman N, Kawai V, del Carpio J, Codova E, Gilman R, Plotkin JB. Retracing micro-epidemics of Chagas disease using epicenter regression. PLoS Computational Biology 7: 1002146 (2011) [pdf]
- Kryazhimskiy S, Draghi J, Plotkin JB. In evolution, the sum is less than its parts. Science 332: 1160-1161 (2011) [pdf]
- Draghi J, Plotkin JB. Molecular evolution: Hidden diversity sparks adaptation. Nature 474: 45-46 (2011) [pdf]
- Draghi J, Parsons TL, Plotkin JB. Epistasis increases the rate of conditionally neutral substitution in an adapting population. Genetics 187: 1139–1152 (2011) [pdf]
- Toole J, Eagle N, Plotkin JB. Spatiotemporal Correlations in Criminal Offense Records. ACM Transactions on Intelligent Systems and Technology 2: 38 (2011) [pdf]
- Kryazhimskiy S, Dushoff J, Bazykin G, Plotkin JB. Prevalence of epistasis in the evolution of influenza A surface proteins. PLoS Genetics 7: 1001301 (2011) [pdf]
- Plotkin JB, Kudla G. Synonymous but not the same: the causes and consequences of codon bias. Nature Reviews Genetics 12: 32-42 (2011) [pdf]
- Plotkin JB. The lives of proteins. Science 331: 683-684 (2011) [pdf]
- Draghi J, Parsons TL, Wagner G, Plotkin JB. Mutational robustness can facilitate adaptation. Nature 426: 353-355 (2010) [pdf]
- Morlon H, Potts M, Plotkin JB. Inferring the dynamics of diversification: a coalescent approach. PLoS Biology 8: 1000493 (2010) [pdf]
- Plotkin JB. Transcriptional regulation is only half the story. Molecular Systems Biology 6: 204 (2010) [pdf]
- Parsons TL, Quince C, Plotkin JB. Some consequences of demographic stochasticity in population genetics. Genetics 185: 1345-1354 (2010) [pdf]
- Vishnoi A, Kryazhimskiy S, Bazykin G, Hannenhalli S, Plotkin JB. Young proteins experience more variable selection pressures than old proteins. Genome Research 20: 1574-1581 (2010) [pdf]
- Salguero–Gomez R, Plotkin JB. The effects of dimensionality on demographic studies using projection matrices. The American Naturalist 176: 710-712 (2010) [pdf]
- Levy MZ, Chavez F, Cornejo del Carpio JG, Vilhena D, McKenzie FE, Plotkin JB. Rational strategies for eliminating a Chagas disease vector. Proceedings of the Royal Society Interface (2010) [pdf]
- Kudla G, Murray AW, Tollervey D, Plotkin JB. Coding-sequence determinants of gene expression in Escherichia coli. Science 324:255-258 (2009) [pdf]
- Kryazhimskiy S, Tkacik G, Plotkin JB. The dynamics of adaptation on correlated fitness landscapes. PNAS 106: 18638-18643 (2009) [pdf]
- Goldstein E, Dushoff J, Ma J, Plotkin JB, Earn DJ, Lipsitch M. Reconstructing influenza incidence by deconvolution of daily mortality time series. PNAS 106: 21825–21829 (2009) [pdf]
- Ndifon W, Plotkin JB, Dushoff J. Environmental impact on the evolutionary accessibility of adaptive phenotypes of a bacterial metabolic network. PLoS Computational Biology 5: 1000472 (2009) [pdf]
- Roy S, Vandenberghe L, Kryazhimskiy S, Grant R, Calcedo R, Yuan X, Keough M, Sandhu A, Wang Q, Medina-Jaszek C, Plotkin JB, Wilson JM. Isolation and characterization of Adenoviruses persistently shed from the gastrointestinal tract of non-human primates. PLoS Pathogens 5:1000503 (2009) [pdf]
- Levy M, Bowman N, Kawai V, Plotkin JB et al. Spatial patterns in discordant diagnostic test results for Chagas disease: links to transmission hotspots. Clinical Infectious Diseases 48:1104-1106 (2009).
- Kryazhimskiy S, Plotkin JB. The population genetics of dN/dS. PLoS Genetics 4: 1000304 (2008) [pdf]
- Desai MM, Plotkin JB. The polymorphism frequency spectrum of finitely many sites under selection. Genetics 180: 2175-2191 (2008) [pdf]
- Parsons TL, Quince C, Plotkin JB. Absorption and fixation times for neutral and quasi-neutral populations with density dependence. Theoretical Population Biology 74: 302-310 (2008) [pdf]
- Kryazhimskiy S, Basykin GA, Plotkin JB, Dushoff J. Directionality in the evolution of influenza A hemagglutinin. Proceedings of the Royal Society B 275: 2455-2464 (2008) [pdf]
- Sethupathy P, Giang H, Plotkin JB, Hannenhalii S. Genome-wide analysis of natural selection on human cis-elements. PLoS One 3: 3137 (2008) [pdf]
- Lucks JB, Nelson DR, Kudla G, Plotkin JB. Genome landscapes and bacteriophage codon usage. PLoS Computational Biology 4:1 (2008) [pdf]
- Wu M, Li J, Engleka K, Zhou B, Lu M, Plotkin JB, Epstein JA. Persistent expression of Pax3 in neural crest causes cleft palate and defective osteogenesis. Journal of Clinical Investigation 118: 2076-2078 (2008)
- Chen-Plotkin AS, Geser F, Plotkin JB, Clark CM, Kwong LK,Yuan W, Grossman M, VanDeerlin V, Trojanowski JQ, Lee VM. Variations in the progranulin gene affect global gene expression in frontotemporal lobar degeneration. Human Molecular Genetics 17 :1349-1362 (2008)
- Fraser HB, Plotkin JB. Using protein complexes to predict phenotypic effects of gene mutation. Genome Biology 8:252 (2007) [pdf]
- Green JL, Plotkin JB. A statistical theory for sampling species abundances. Ecology Letters 10: 1037-1045 (2007) [pdf]
- Plotkin JB, Fraser HB. Assessing the determinants of evolutionary rates in the presence of noise. Molecular Biology and Evolution 24: 1113-1121 (2007) [pdf]
- Dushoff J, Plotkin JB, Viboud C, Simonesen L, Miller M. Vaccinating to protect a vulnerable subpopulation. PLoS Medicine 4:174 (2007) [pdf]
- Plotkin JB, Dushoff J, Desai MM, Fraser HB. Codon usage and selection on proteins. Journal of Molecular Evolution 63: 635-553 (2006) [pdf]
- Plotkin JB, Dushoff J, Desai MM, Fraser HB. Estimating selection pressures from limited comparative data. Molecular Biology and Evolution 23: 1457-1459 (2006) [pdf]
- Dushoff J, Plotkin JB, Viboud C, Earn JD, Simonsen L. Mortality due to influenza in the US -- an annualized approach to estimation using multiple-cause mortality data. American Journal of Epidemiology 163: 181-187 (2006) [pdf]
- Seidler T, Plotkin JB. Seed dispersal and spatial pattern in tropical trees. PLoS Biology 4: 344- (2006) [pdf]
- Ng K, Soon LL, Saw LG, Plotkin JB, Koh CL. Spatial structure and genetic diversity of three tropical tree species with different habitat preferences within a natural forest. Tree Genetics and Genomes 2: 121-131 (2006) [pdf]
- HB Fraser, P Khaitovich, JB Plotkin, S Paabo, MB Eisen. Aging and gene expression in the primate brain. PLoS Biology 3: 274- (2005) [pdf]
- Lukhtanov V, Kandul N, Plotkin JB, Dantchenko A, Haig D, Pierce N. Reinforcement of pre-zygotic isolation and karyotype evolution in Agrodiaetus butterflies. Nature 436: 385-389 (2005) [pdf]
- Plotkin JB, Dushoff J, Fraser HB. Codon bias and selection on single genomes -- reply. Nature 433 E7-E8 (2005) [pdf]
- Dushoff J, Plotkin JB, Levin SA, Earn DE. Dynamic resonance can explain the seasonality of influenza incidence. PNAS 101: 16915-16916 (2004) [pdf]
- Plotkin JB, Robins H, Levine A. Tissue specific codon usage and the expression of human genes. PNAS 101: 12588-12591 (2004) [pdf]
- Plotkin JB, Dushoff J, Fraser HB. Detecting selection using a single genome sequence of M. tuberculosis and P. falciparum. Nature 428: 942-945 (2004) [pdf]
- Levin SA, Dushoff J, Plotkin JB. Evolution and persistence of Influenza A and other diseases. Mathematical Biosciences 188: 12-28 (2004) [pdf]
- Plotkin JB, Dushoff J. Codon bias and frequency-dependent selection on the hemagglutinin epitopes of Influenza A virus. PNAS 100: 7152-7157 (2003) [pdf]
- Plotkin JB, Dushoff J, Levin SA. Hemagglutinin sequence clusters and the antigenic evolution of Influenza A virus. PNAS 99: 6263-6268 (2002) [pdf]
- Plotkin JB, Nowak MA. The different effects of apoptosis and DNA repair on tumorigenesis. Journal of Theoretical Biology 214: 453-467 (2002) [pdf]
- Krakauer D, Plotkin JB. Redundancy, anti-redundancy, and the stability of genomes. PNAS 99: 1405-1409 (2002) [pdf]
- Krakauer D, Plotkin JB. Principles and parameters of molecular robustness. In Robust Design, ed. Erica Jen, Santa Fe Press (2002) [pdf]
- Plotkin JB, Muller-Landau H. Sampling the species composition of a landscape. Ecology 83: 3344-3356 (2002) [pdf]
- Plotkin JB, Chave J, Ashton PS. Cluster analysis of spatial patterns in Malaysian tree species. The American Naturalist 160: 629-644 (2002) [pdf]
- Potts MD, Ashton PS, Kaufman LS, Plotkin JB. Habitat patterns in tropical rain forests: a comparison of 105 plots in Northwest Borneo. Ecology 83: 2782?2797 (2002) [pdf]
- Plotkin JB, Levin SA. The spatial distribution and abundances of species: Lessons from tropical forests. Comments on Theoretical Biology 6: 251-278 (2001) [pdf]
- Plotkin JB, Nowak MA. Major transitions in language evolution. Entropy 4: 227-246 (2001)
- Potts MD, Plotkin JB, Lee HS, Manokaran N. Sampling biodiversity: effects of plot shape. The Malaysian Forester 64: 29-34 (2001)
- Plotkin JB, Potts M, Yu D, Bunyavejchewin S, Condit R, Foster R, Hubbell S, LaFrankie J, Manokaran N, Seng L, Sukumar R, Nowak MA, Ashton PS. Predicting species diversity in tropical forests. PNAS 97:10850-10854 (2000) [pdf]
- Nowak M, Plotkin JB, Jansen V. The evolution of syntactic communication. Nature 404: 495-498 (2000) [pdf]
- Plotkin JB, Nowak MA. Language evolution and information theory. Journal of Theoretical Biology 205: 147-159 (2000) [pdf]
- Plotkin JB, Potts M, Leslie N, Manokaran N, LaFrankie J, Ashton P. Species-area curves, spatial aggregation, and habitat specialization in tropical forests. Journal of Theoretical Biology 207:81-99 (2000) [pdf]
- Nowak MA, Plotkin JB, Krakauer D. The evolutionary language game. Journal of Theoretical Biology 200: 147-162 (1999) [pdf]
- Harrison RD, Tan S, Plotkin JB, Slik F, Detto M, Brenes T, Itoh A, Davis SJ. Consequences of defaunation for a tropical tree community. Ecology Letters 16: 687–694 (2013) [pdf]
- 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
We gratefully acknowledge funding from: