Studies On The Relative Contribution Of Different Factors That Influence Codon Usage Patterns In Different Organisms

Abstract

Codon usage bias (CUB) and mRNA structural stability are important intrinsic features of mRNA that correlate positively with mRNA expression level. However, it remains unclear whether the mRNA expression level can be regulated by adjusting these two parameters, influencing the mRNAs’ structure. Here we explored the influence of CUB and mRNA structural stability on mRNA expression levels in Saccharomyces cerevisiae, using both wild type and computationally mutated mRNAs. Although in wild type, both CUB and mRNA stability positively regulate the mRNA expression level, any deviation from natural situation breaks such equilibrium. The naturally occurring codon composition is responsible for optimizing the mRNA expression, and under such composition, the mRNA structure having highest stability is selected by nature. Codon choice which we see in the organisms have shown to evolve from its close ancestors. These changes that happen can be either synonymous or non-synonymous in nature. It has been seen that chaperones act as buffers and help in having these changes. As chaperones facilitate protein folding in the mutated proteins they enable evolution to be sustained. But, in our study we found that chaperone clients evolved slowly as compared to non-client proteins. The study was done in Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens and Thermus aquaticus. We included T.aquaticus (extremophile) to look for any natural overexpression of chaperones that may have helped in the evolution of genes but, they too showed slower evolutionary rates. Slower evolutionary rates, tends to provide codon usage restriction which has seen to result in a smoother, rapid and accurate translations. Looking from an evolutionary perspective it seems codon usage bias may result due to accuracy requirements in translation but, also a cell can’t survive without the appropriate abundance in transcripts and proteins. We did a study in codons and anti-codons present in Saccharomyces cerevisiae. It was found that tRNA pool is affecting the synonymous codon usage choices which in turn is affecting the mRNA abundance and its stability. These stable mRNAs positively affects ribosomal density that finally takes care of the protein abundance. The work elaborately presents the influence of all these factors.