Natural selection retains overrepresented out-of-frame stop codons against frameshift peptides in prokaryotes

BMC Genomics

Research Article

Hoi-Wah Tsoi¹  Esther PT Lam¹  Kwok-Yung Yuen²  Herman Tse²  James J Cai³ 

[1] Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Hong Kong, China;Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Hong Kong, China;Research Centre of Infection and Immunity, The University of Hong Kong, Hong Kong, China;Department of Biology, Stanford University, Stanford, California, USA;Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, Texas, USA;

关键词: Codon;    Codon Usage;    Codon Position;    Synonymous Codon;    Codon Usage Bias;   

DOI  :  10.1186/1471-2164-11-491

 received in 2010-03-13, accepted in 2010-09-09,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundOut-of-frame stop codons (OSCs) occur naturally in coding sequences of all organisms, providing a mechanism of early termination of translation in incorrect reading frame so that the metabolic cost associated with frameshift events can be reduced. Given such a functional significance, we expect statistically overrepresented OSCs in coding sequences as a result of a widespread selection. Accordingly, we examined available prokaryotic genomes to look for evidence of this selection.ResultsThe complete genome sequences of 990 prokaryotes were obtained from NCBI GenBank. We found that low G+C content coding sequences contain significantly more OSCs and G+C content at specific codon positions were the principal determinants of OSC usage bias in the different reading frames. To investigate if there is overrepresentation of OSCs, we modeled the trinucleotide and hexanucleotide biases of the coding sequences using Markov models, and calculated the expected OSC frequencies for each organism using a Monte Carlo approach. More than 93% of 342 phylogenetically representative prokaryotic genomes contain excess OSCs. Interestingly the degree of OSC overrepresentation correlates positively with G+C content, which may represent a compensatory mechanism for the negative correlation of OSC frequency with G+C content. We extended the analysis using additional compositional bias models and showed that lower-order bias like codon usage and dipeptide bias could not explain the OSC overrepresentation. The degree of OSC overrepresentation was found to correlate negatively with the optimal growth temperature of the organism after correcting for the G+C% and AT skew of the coding sequence.ConclusionsThe present study uses approaches with statistical rigor to show that OSC overrepresentation is a widespread phenomenon among prokaryotes. Our results support the hypothesis that OSCs carry functional significance and have been selected in the course of genome evolution to act against unintended frameshift occurrences. Some results also hint that OSC overrepresentation being a compensatory mechanism to make up for the decrease in OSCs in high G+C organisms, thus revealing the interplay between two different determinants of OSC frequency.

【 授权许可】

Unknown   
© Tse et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.