SCUMBLE: a method for systematic and accurate detection of codon usage bias by maximum likelihood estimation.

Nucleic Acids Res

Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, California 94158, USA.

Published: June 2008

The genetic code is degenerate--most amino acids can be encoded by from two to as many as six different codons. The synonymous codons are not used with equal frequency: not only are some codons favored over others, but also their usage can vary significantly from species to species and between different genes in the same organism. Known causes of codon bias include differences in mutation rates as well as selection pressure related to the expression level of a gene, but the standard analysis methods can account for only a fraction of the observed codon usage variation. We here introduce an explicit model of codon usage bias, inspired by statistical physics. Combining this model with a maximum likelihood approach, we are able to clearly identify different sources of bias in various genomes. We have applied the algorithm to Saccharomyces cerevisiae as well as 325 prokaryote genomes, and in most cases our model explains essentially all observed variance.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441815PMC
http://dx.doi.org/10.1093/nar/gkn288DOI Listing

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