Codon usage of highly expressed genes affects proteome-wide translation efficiency

Area of Science:

• Genetics
• Molecular Biology
• Bioinformatics

Background:

• The genetic code shows redundancy, but synonymous codons are not equally frequent (codon usage bias).
• Synonymous codon changes can affect gene expression (cis-effects).
• The impact of codon composition on other genes' translation efficiency is less understood.

Purpose of the Study:

• To investigate how codon usage bias influences the cellular economy of translation.
• To determine if manipulating codon usage in highly expressed genes affects cellular fitness and translation efficiency.

Main Methods:

• Massively converted abundant codons to rare synonymous counterparts in highly expressed Escherichia coli genes.
• Observed effects on cellular fitness and translation efficiency.
• Tested phenotypic rescue by increasing tRNA supply for specific codons.

Main Results:

• Perturbing codon usage reduced cellular fitness and translation efficiency in genes with high initiation rates and enriched manipulated codons.
• Phenotypes were alleviated by increasing the supply of tRNA for the demanded codon.
• This supports the hypothesis that codon usage is selected to maintain global translation efficiency.

Conclusions:

• Codon usage bias in highly expressed genes is crucial for maintaining efficient global protein translation.
• Evolutionary selection favors codon usage that optimizes resource allocation for translation.
• Understanding codon usage bias is key to comprehending cellular economy and gene expression regulation.