The genetic code is highly redundant with multiple codons coding for a particular amino acid. Even before the first genome was sequenced, it became apparent that synonymous codons of an amino acid are used unequally in coding sequences. Ever since, the relative importance of adaptive and non-adaptive factors affecting such codon usage bias (CUB) have been actively debated. The lack of a coherent framework to test alternate hypotheses, and a focus on heuristic indices have hindered our ability to disentangle the effects of different evolutionary pressures on codon bias.

We are developing a framework that integrates mechanistic models of protein translation with population-genetics models to understand and distinguish the effects of various adaptive and non-adaptive forces on the evolution of codon biases. Such models will allow us to make quantitative predictions on how codon usage would change with varying mutation and selection regimes.


A codon model of nucleotide substitution with selection on synonymous codon usage. Kubatko et al. Mol Phylo Evol 2016

Estimating gene expression and codon specific translational efficiencies, mutation biases, and selection coefficients from genomic data alone. Gilchrist et al. Genome Biol Evol 2015

Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Xu et al. Nature 2013

Weak 5′-mRNA Secondary Structures in Short Eukaryotic Genes. Ding et al. Genome Biol Evol 2012

Explaining complex codon usage patterns with selection for translational efficiency, mutation bias, and genetic drift. Shah & Gilchrist PNAS 2011

Effect of correlated tRNA abundances on translation errors and evolution of codon usage bias. Shah & Gilchrist PLOS Genet 2010

Measuring and detecting molecular adaptation in codon usage against nonsense errors during protein translation. Gilchrist et al. Genetics 2009