Bioinformatics Seminar

An occasional seminar series on bioinformatics, at Berkeley and beyond!

Title: Inferring Evolutionary Histories and Predicting Functional Residues by Modeling Evolutionary Heterogeneity

Speaker: Bryan Kolaczkowski, Ph.D, Center for Ecology and Evolutionary Biology, University of Oregon

Time: 2:00-3:00pm, Wednesday, March 19th, 2008

Place: 321 Stanley Hall

Abstract:
One of the central questions in molecular evolution is, ‘How are similarities and differences among species generated by evolutionary changes in DNA and protein molecules?’ Answering this question requires not only a detailed understanding of the evolutionary relationships among species but also the ability to separate functionally important substitutions from those that are largely neutral. Here I introduce a phylogenetic model of site-specific evolutionary rate changes and describe how it can be used to 1) improve the accuracy of inferred evolutionary relationships and 2) predict the specific substitutions responsible for important functional shifts in protein evolution. The motivation for the development of this model is the observation that different positions in the molecule regularly change their rates of evolution as they evolve. As I show, these changes in site-specific rates not only interfere with accurate phylogenetic inference but also provide clues as to which sites are likely to be responsible for shifts in molecular function. The model incorporates site-specific rate changes by analyzing a sequence alignment using a number of independently optimized branch length sets along the tree rather than the single set of branch lengths used in current models. I show that the incorporation of evolutionary rate changes produces more accurate phylogenies than existing methods. The model can also be used to assign specific sites in the alignment to particular branch length sets, providing an estimate of site-specific evolutionary dynamics that can be exploited to predict the functional importance of each site.



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