DIMACS Workshop on Phylogenetic Trees and Rapidly Evolving Pathogens

June 21 - 22, 2006
DIMACS Center, CoRE Building, Rutgers University

Allen Rodrigo, University of Auckland, a.rodrigo@auckland.ac.nz
Mike Steel, University of Canterbury, M.Steel@math.canterbury.ac.nz
Presented under the auspices of the Special Focus on Computational and Mathematical Epidemiology.

DIMACS Tutorial on Phylogenetic Trees and Rapidly Evolving Pathogens, June 19 - 20, 2006.

DIMACS Working Group on Phylogenetic Trees and Rapidly Evolving Diseases II, June 23, 2006.

DIMACS Working Group on Phylogenetic Trees and Rapidly Evolving Diseases I, September 7 - 8, 2004.

This workshop will build on phylogenetic methods developed by computational biologists to explore ways in which such methods can be applied and developed to shed new light on the origin, evolution, and likely future development of viruses and other pathogens. Phylogeny is now a central tool for studies into the origin and diversity of viruses such as HIV (see, e.g., [Pybus, Rambaut and Harvey (2000), Rambaut, Robertson, Pybus, Peeters and Holmes (2001),]) and dengue fever virus [Rambaut (2000)]. These and other investigations have provided new insights, such as identifying the possible pattern of transfer of HIV-type viruses between primate species. Phylogenetic techniques have also proved useful in mapping the evolution of different strains of the human influenza A virus [Bush, Bender, Subbarao, Cox and Fitch (1999a), Bush, Fitch, Bender and Cox (1999b)], with the goal of predicting which strain is most likely to cause future epidemics, with applications to vaccine development. Many of the phylogenetic techniques in use were originally developed to investigate more traditional and well-behaved evolutionary problems, where historical relationships are typically represented by a binary tree with a small number of species appearing as the leaves (tip vertices). In epidemiology the picture is more complex and this observation underlies the task of this working group. Even if there is a single underlying tree, it may typically have thousands of vertices, and many of these may be of high degree. Furthermore, data may be available not just for the species at the leaves of the tree, but for species distributed at vertices throughout the tree, particularly when the evolution of a virus is studied by serial sampling in patients. This is true for retroviruses which have a very high substitution rate, and whose molecular evolution may be up to 106 times more rapid than eukaryotic or prokaryotic genes [Drummond and Rodrigo (2000), Rodrigo, Shpaer, Delwart, Iversen, Gallo, Jurgen Brojatsch, Hirsch, Walker and Mullins (1999), Shankarappa, Margolick, Gange, Rodrigo, Upchurch, Farzadegan, Gupta, Rinaldo, Learn, He, Huang and Mullins (1999)]. New methods for dealing with these complications will be investigated. To complicate the picture further, it may well be more appropriate to represent the evolution of a virus by a collection of trees, or by a digraph (or network) to recognize the "quasispecies" nature of viruses, such as in the application of split decomposition by Dopazo, Dress, and von Haeseler [Dopazo, Dress and von Haeseler (1993)]; we shall pursue this direction of research. Relating population genetics considerations (currently handled by the "coalescent" model) to phylogeny considerations is also potentially useful [Rodrigo and Felsenstein (1999)]. However, even here, theory has yet to be developed. For instance, the fact that retroviral evolution occurs within a host means that viral sequences sampled from different hosts must take account of the different dynamics of between-host transmission histories and within-host viral genealogies [Rodrigo (1999)]. This has consequences for the inference of epidemiological parameters based on viral sequences obtained from several hosts, and we will investigate them. Finally, if one wishes to test particular epidemiological hypotheses it would be helpful to have techniques that avoid having to fix attention on one particular tree. This suggests devising fast methods that would average the quantities of interest over all likely trees, weighted by how well they describe the data - a challenge for modern computational tools and our working group.


Bush, R.M., Bender, C.A., Subbarao, K. Cox, N.J., and Fitch, W.M. (1999a), "Predicting the evolution of human influenza A," Science, 286, 1921-1925.

Bush, R.M., Fitch, W.M., Bender, C.A., and Cox, N.J. (1999b), "Positive selection on the H3 Hemagglutinin gene of human influenza virus A," Mol. Biol. Evol., 16, 1457-1465.

Dopazo, J., Dress, A., and von Haeseler, A. (1993), "Split decomposition: A technique to analyse viral evolution," Proc. Natl. Acad. Sci. USA, 90, 10320-10324.

Drummond, A., and Rodrigo, A.G. (2000), "Reconstructing genealogies of serial samples under the assumption of a molecular clock using serial-sample UPGMA (sUPGMA)," Molecular Biology and Evolution, 17, 1807-1815.

Pybus, O. Rambaut, A., and Harvey, P.H. (2000), "An integrated framework for the inference of viral population history from reconstructed genealogies," Genetics, 155, 1429-1437.

Rambaut, A. (2000), "Estimating the rate of molecular evolution: incorporating non-contemporaneous sequences into maximum likelihood phylogenies," Bioinformatics, 16, 395-399.

Rambaut, A., Robertson, D.L., Pybus, O.G., Peeters, M., and Holmes, E. (2001), "Phylogeny and the origin of HIV-1," Nature, 410, 1047-1048.

Rodrigo, A.G. (1999), "HIV evolutionary genetics [Commentary]," Proceedings of the National Academy of Sciences, 96, 10559-10561.

Rodrigo, A.G., and Felsenstein, J. (1999), "Coalescent approaches to HIV-1 Population Genetics," in K.A. Crandall (ed.), Molecular Evolution of HIV, Johns Hopkins University Press.

Rodrigo, A.G., Shpaer, E.G., Delwart, E.L., Iversen, A.K.N., Gallo, M.V., Jurgen Brojatsch, J., Hirsch, M.S., Walker, B.D., and Mullins, J.I. (1999), "Coalescent estimates of HIV-1 generation time in vivo," Proceedings of the National Academy of Science, 96, 2187-2191.

Shankarappa, R., Margolick, R.B., Gange, S.J., Rodrigo, A.G., Upchurch, D., Farzadegan, H., Gupta, P., Rinaldo, C.R., Learn, G.H., He, X., Huang, X-L., and Mullins, J.I. (1999), "Consistent viral evolutionary changes associated with progression of HIV-1 infection," Journal of Virology, 73, 10489-10502.

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Document last modified on December 14, 2005.