This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
Nucleotide substitution is an important mechanism by which genomes change over evolutionary time. This project seeks to improve our understanding of nucleotide substitution by focusing on an aspect that is currently poorly characterized: how the context of neighboring nucleotides biases substitution. At present the best described bias effects are those due to immediately adjacent nucleotides. However, it is known that more distant nucleotides also affect substitution. The goal of the project is to develop and apply a method to systematically characterize more distant context effects. The information obtained can later be used to improve models of nucleotide substitution. Such improvements could potentially contribute to areas such as reconstructing phylogeny and inferring which parts of the genome are functional.
The project will contribute to the training of biologists with strong quantitative backgrounds. It will be carried out by undergraduate students at Harvey Mudd College (HMC), a selective liberal arts college focused on science and engineering. Students at the college receive unusually broad training in the physical sciences, mathematics and computer science as part of the college's core curriculum. Such students have a great deal to offer biology. Molecular evolution and computational biology are natural areas for them to apply their skills. This project helps introduce students to these disciplines through research opportunities and connections with coursework. Because 25% of HMC's graduates receive a Ph.D. within nine years of graduation, the project work will contribute to the training of a new generation of biological researchers with strong quantitative skills. An additional impact is that the software developed for this project will be distributed freely on the web.