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OVERVIEW

We use mathematics and computation to study questions in evolutionary biology and ecology. Research in the group 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, 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 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 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.


CURRENT



Joshua Plotkin is the principal investigator. [CV]




Todd Parsons completed his PhD in applied mathematics at the University of Toronto, on stochastic population models.




Jeremy Draghi completed his PhD in biology at Yale, on the evolution of evolvability.




Helene Morlon completed her PhD in environmental science at the University of Bordeaux, on mathematical ecology.




Sergey Kryazhimskiy completed his PhD in applied mathematics at Princeton, on models of influenza dynamics and evolution.




Michael Levy completed his PhD in biology at Emory University, on the transmission of Chagas disease in Peru.




Anchal Vishnoi completed her PhD in Bioinformatics at JNU, New Delhi on comparitive evolutionary genomics. (Joint with Sridhar Hannenhalli lab)




Gasper Tkacik completed his PhD in physics at Princeton, on information transmission in biological networks. (Joint with Nelson and Balasubramanian groups)




Serena Rezny is a graduate student in Applied Mathematics at Penn. She received a BA in Applied Mathematics from Harvard, and an MS in Statistics from the University of Chicago.




Ricky Der is a graduate student in mathematics at Penn, joint with Charles Epstein. He completed his BS and MS in electrical engineering at McGill University.




Erica Foley is a graduate student in biology at Penn, joint with Dustin Brisson. She completed her BS in Biology at Penn State.




Sebastian Akle is a senior Biology major at Penn.



ALUMNI



Grzegorz Kudla is currently a fellow at the University of Edinburgh.




Daril Vilhena is currently a graduate student at the University of Washington, in Biology.



RECENT VISITORS

Lena Gieschen, David Krakauer.



RECENT COLLABORATORS

Charlie Epstein, Sridhar Hannenhalli, Jonathan Dushoff, David Earn, Hunter Fraser, Julius Lucks, David Nelson, Jessica Green, Michael Desai, Andrew Murray, Tristram Seidler, Matthew Potts, Harlan Robins, Arnie Levine, Mark Lipsitch, David Krakauer, Alice Chen-Plotkin, Christopher Quince

POSTDOCS

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.


GRADUATE STUDENTS

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.


UNDERGRADUATE STUDENTS

Students with a strong computational background and an interest in evolution or ecology are encouraged to contact Dr. Plotkin regarding the possibility of for-credit or for-pay term or summer projects. Send an email explaining what you hope to get out of an undergraduate research experience, along with brief CV, including GPA, to jplotkin (at) sas.upenn.edu.


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

46. Goldstein E, Dushoff J, Ma J, Plotkin JB, Earn DJ, Lipsitch M. Deconvolution and estimation for epidemic data: death curves, incidence curves, infectivity ratios and reproductive numbers. Proc. Natl. Acad. Sci. USA (in press).

45. Kryazhimskiy S, Tkacik G, Plotkin JB. The dynamics of adaptation on correlated fitness landscapes. Proc. Natl. Acad. Sci. USA (in press) [pdf]

44. Kudla G, Murray AW, Tollervey D, Plotkin JB. Coding-sequence determinants of gene expression in Escherichia coli. Science 324:255-258 (2009). [pdf]

43. 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]

42. 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]

41. 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).

40. Kryazhimskiy S, Plotkin JB. The population genetics of dN/dS. PLoS Genetics 4: 1000304 (2008) [pdf]

39. Desai MM, Plotkin JB. The polymorphism frequency spectrum of finitely many sites under selection. Genetics 180: 2175-2191 (2008) [pdf]

38. 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]

37. Kryazhimskiy S, Basykin GA, Plotkin JB, Dushoff J. Directionality in the evolution of influenza A hemagglutinin. Proceedings of the Royal Society 275: 2455-2464 (2008) [pdf]

36. Sethupathy P, Giang H, Plotkin JB, Hannenhalii S. Genome-wide analysis of natural selection on human cis-elements. PLoS One 3: 3137 (2008) [pdf]

35. Lucks JB, Nelson DR, Kudla G, Plotkin JB. Genome landscapes and bacteriophage codon usage. PLoS Computational Biology 4:1 (2008) [pdf]

34. 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)

33. 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)

32. Fraser HB, Plotkin JB. Using protein complexes to predict phenotypic effects of gene mutation. Genome Biology 8:252 (2007) [pdf]

31. Green JL, Plotkin JB. A statistical theory for sampling species abundances. Ecology Letters 10: 1037-1045 (2007) [pdf]

30. Plotkin JB, Fraser HB. Assessing the determinants of evolutionary rates in the presence of noise. Molecular Biology and Evolution 24: 1113-1121 (2007) [pdf]

29. Dushoff J, Plotkin JB, Viboud C, Simonesen L, Miller M. Vaccinating to protect a vulnerable subpopulation. PLoS Medicine 4:174 (2007) [pdf]

28. Plotkin JB, Dushoff J, Desai MM, Fraser HB. Codon usage and selection on proteins. Journal of Molecular Evolution 63: 635-553 (2006) [pdf]

27. Plotkin JB, Dushoff J, Desai MM, Fraser HB. Estimating selection pressures from limited comparative data. Molecular Biology and Evolution 23: 1457-1459 (2006) [pdf]

26. 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]

25. Seidler T, Plotkin JB. Seed dispersal and spatial pattern in tropical trees. PLoS Biology 4: 344- (2006) [pdf]

24. 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]

23. HB Fraser, P Khaitovich, JB Plotkin, S Paabo, MB Eisen. Aging and gene expression in the primate brain. PLoS Biology 3: 274- (2005) [pdf]

22. 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]

21. Plotkin JB, Dushoff J, Fraser HB. Codon bias and selection on single genomes -- reply. Nature 433 E7-E8 (2005) [pdf]

20. Dushoff J, Plotkin JB, Levin SA, Earn DE. Dynamic resonance can explain the seasonality of influenza incidence. Proceedings of the National Academy of Sciences 101: 16915-16916 (2004) [pdf]

19. Plotkin JB, Robins H, Levine A. Tissue specific codon usage and the expression of human genes. Proceedings of the National Academy of Sciences 101: 12588-12591 (2004) [pdf]

18. 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]

17. Levin SA, Dushoff J, Plotkin JB. Evolution and persistence of Influenza A and other diseases. Mathematical Biosciences 188: 12-28 (2004) [pdf]

16. Plotkin JB, Dushoff J. Codon bias and frequency-dependent selection on the hemagglutinin epitopes of Influenza A virus. Proceedings of the National Academy of Sciences 100: 7152-7157 (2003) [pdf]

15. Plotkin JB, Dushoff J, Levin SA. Hemagglutinin sequence clusters and the antigenic evolution of Influenza A virus. Proceedings of the National Academy of Sciences 99: 6263-6268 (2002) [pdf]

14. Plotkin JB, Nowak MA. The different effects of apoptosis and DNA repair on tumorigenesis. Journal of Theoretical Biology[pdf]

13. Krakauer D, Plotkin JB. Redundancy, anti-redundancy, and the stability of genomes. Proceedings of the National Academy of Sciences 99: 1405-1409 (2002) [pdf]

12. Krakauer D, Plotkin JB. Principles and parameters of molecular robustness. In Robust Design, ed. Erica Jen, Santa Fe Press (2002) [pdf]

11. Plotkin JB, Muller-Landau H. Sampling the species composition of a landscape. Ecology 83: 3344-3356 (2002) [pdf]

10. Plotkin JB, Chave J, Ashton PS. Cluster analysis of spatial patterns in Malaysian tree species. The American Naturalist 160: 629-644 (2002) [pdf]

9. 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]

8. Plotkin JB, Levin SA. The spatial distribution and abundances of species: Lessons from tropical forests. Comments on Theoretical Biology 6: 251-278 (2001) [pdf]

7. Plotkin JB, Nowak MA. Major transitions in language evolution. Entropy 4: 227-246 (2001)

6. Potts MD, Plotkin JB, Lee HS, Manokaran N. Sampling biodiversity: effects of plot shape. The Malaysian Forester 64: 29-34 (2001)

5. 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. Proceedings of the National Academy of Sciences 97:10850-10854 (2000) [pdf]

4. Nowak M, Plotkin JB, Jansen V. The evolution of syntactic communication. Nature 404: 495-498 (2000) [pdf]

3. Plotkin JB, Nowak MA. Language evolution and information theory. Journal of Theoretical Biology 205: 147-159 (2000) [pdf]

2. 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]

1. Nowak MA, Plotkin JB, Krakauer D. The evolutionary language game. Journal of Theoretical Biology 200: 147-162 (1999) [pdf]



We use mathematics and computation to study questions in evolutionary biology and ecology. Research in the group is primarily concerned with the origin and maintenance of genetic variation within populations. (read more)