RNA folding is unaffected by the nonrandom degenerate codon choice

Area of Science:

• Molecular Biology
• Genetics
• Bioinformatics

Background:

• Nonrandom codon usage is a known phenomenon in various organisms.
• A prevailing hypothesis suggests that codon usage bias is driven by the need for increased messenger RNA (mRNA) stability.
• This stability is thought to be achieved through specific secondary structures formed by mRNA.

Purpose of the Study:

• To investigate the correlation between nonrandom codon usage and mRNA secondary structure stability across a set of 22 genes.
• To determine if mRNA stability is a universal explanation for codon usage bias.

Main Methods:

• Analysis of codon usage patterns in 22 selected genes.
• Assessment of mRNA secondary structure stability for these genes.
• Comparison of preferred degenerate codons with mRNA stability metrics.

Main Results:

• A correlation between preferred codons and mRNA stability was observed in only a few gene families: histones, globins, and the rat preproinsulin gene.
• Histone and globin genes, ancient eukaryotic genes, exhibit high GC content (around 56%) compared to the eukaryotic average (42%).
• This high GC content in ancient genes influences codon choice, leading to more stable mRNA folding.

Conclusions:

• The hypothesis that nonrandom codon usage is solely explained by increased mRNA stability is not universally supported.
• The stability of mRNA secondary structures plays a role in codon usage bias, particularly in evolutionarily conserved gene families like histones and globins.
• High GC content in ancient genes is a significant factor contributing to both codon usage patterns and mRNA stability.