Selection on codon bias in yeast: a transcriptional hypothesis

Abstract

Codons that code for the same amino acid are often used with unequal frequencies. This phenomenon is termed codon bias. Here, we report a computational analysis of codon bias in yeast using experimental and theoretical genome-wide data. We show that the most used codons in highly expressed genes can be predicted by mRNA structural data and that the codon choice at each synonymous site within an mRNA is not random with respect to the local secondary structure. Because we also found that the folding stability of intron sequences is strongly correlated with codon bias and mRNA level, our results suggest that codon bias is linked to mRNA folding structure through a mechanism that, at least partially, operates before pre-mRNA splicing. Consistent with this, we report evidence supporting the adaptation of the tRNA pool to the codon profile of the most expressed genes rather than vice versa. We show that the correlation of codon usage with the gene expression level also includes the stop codons that are normally not decoded by aminoacyl-tRNAs. The results reported here are consistent with a role for transcriptional forces in driving codon usage bias via a mechanism that improves gene expression by optimizing mRNA folding structures.

Genomic, Transcriptomic, and Proteomic Analysis Provide Insights Into the Cold Adaptation Mechanism of the Obligate Psychrophilic Fungus Mrakia psychrophila

“…There are several reasons for the codon usage bias in M. psychrophila . First, codon usage bias might influence mRNA folding structure (Trotta 2013) and special codon usage may facilitate translation at low temperatures. Second, codon usage bias may have coevolved with the copy number of the corresponding tRNAs.…”

Synonymous codons, ribosome speed, and eukaryotic gene expression regulation

“…This may restrict codon choice further, although codons decoded by abundant tRNAs often match the general GC content well. Other associations that have been detected in codon usage patterns include the optimisation of transcriptional efficiency [105], correlation with recombination activity [106], organisation of transcription factor binding [107], and start codon context [108,109].…”

Recurrent positive selection and heterogeneous codon usage bias events leading to coexistence of divergent pigeon circoviruses

“…However, changes in expression levels of genes in relation to synonymous codon usage could be relevant to the molecular adaptation in response to natural selection (Hershberg & Petrov, 2008;Plotkin & Kudla, 2011). Translational selection on synonymous codon usage has been found to be strongly correlated with gene expression (Ran & Higgs, 2012;Trotta, 2013). Therefore, codon usage bias (CUB) becomes a genetic manner to reflect the translational accuracy and efficiency in the light of evolution (Angov, 2011;Shah & Gilchrist, 2011;Sharp et al, 2010).…”