Our research integrates mechanistic models of biological processes with population-genetic models to understand the forces shaping genome architecture. The research program is focused on four areas of biology:
1. Evolution of codon usage bias and protein translation – By building detailed biophysical models of protein translation, we seek to explain the mechanistic bases of protein production in a cell as well as the factors that drive the evolution of biased codon usage.
2. Epistasis in protein evolution – By combining models of protein stability with a population-genetic framework, we seek to explain how mutations individually and collectively influence protein evolution.
3. Evolution of mutation rates – By building biophysical models of DNA structures and their interactions with DNA-binding proteins, we work to understand what sets mutation rates and biases.
4. Phylogenetics – We work to identify regions of diversification rate variation, and to integrate models of selection on codon usage into phylogenetic methods.
Weinberg DE*, Shah P*, et al. Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation. Cell Reports (2016)
Shah P*, McCandlish DM* and Plotkin JB. Contingency and entrenchment in protein evolution under purifying selection.PNAS 112: E3226–E3235 (2015)
Shah P, et al. Rate-limiting steps in yeast protein translation.Cell 153 (7): 1589-1601 (2013)
Xu Y, Ma P, Shah P, et al. Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Nature 495: 116-120 (2013)
Shah P, and Gilchrist MA. Explaining complex codon usage patterns with selection for translational efficiency, mutation bias, and genetic drift. PNAS 108: 10231-6 (2011)
Shah P, and Gilchrist MA. Effect of correlated tRNA abundances on translation errors and the evolution of codon usage bias.PLOS Genetics 6 (9): e1001128 (2010)