Mechanisms governing codon usage bias and the implications for protein expression in the chloroplast of Chlamydomonas reinhardtii

Abstract

Chloroplasts possess a considerably reduced genome that is decoded via an almost minimal set of tRNAs. These features make an excellent platform for gaining insights into fundamental mechanisms that govern protein expression. Here, we present a comprehensive and revised perspective of the mechanisms that drive codon selection in the chloroplast of Chlamydomonas reinhardtii and the functional consequences for protein expression. In order to extract this information, we applied several codon usage descriptors to genes with different expression levels. We show that highly expressed genes strongly favor translationally optimal codons, while genes with lower functional importance are rather affected by directional mutational bias. We demonstrate that codon optimality can be deduced from codon-anticodon pairing affinity and, for a small number of amino acids (leucine, arginine, serine, and isoleucine), tRNA concentrations. Finally, we review, analyze, and expand on the impact of codon usage on protein yield, secondary structures of mRNA, translation initiation and termination, and amino acid composition of proteins, as well as cotranslational protein folding. The comprehensive analysis of codon choice provides crucial insights into heterologous gene expression in the chloroplast of C. reinhardtii, which may also be applicable to other chloroplastcontaining organisms and bacteria.

Analysis of Codon Usage Bias in Xyloglucan Endotransglycosylase (XET) Genes

“…The biological process of genetic information from mRNA to protein depends on codon coding [ 34 ]. Codon is an important part of the output of nucleic acid information [ 35 , 36 ]. Previous research has found that codon usage bias is mainly influenced by mutation pressure and natural selection [ 37 ].…”

Comprehensive analysis of codon bias in 13 Ganoderma mitochondrial genomes

“…Codon bias can have a significant impact on a variety of cellular processes and characteristics, such as transcription, translation efficiency and accuracy, mRNA stability, and protein expression, structure, function, and folding during cotranslation ( Chaney and Clark, 2015 ; Fages-Lartaud et al, 2022 ). Codon bias has an influence on transcription due to its effect on chromatin structure and mRNA folding, which in turn affects translation efficiency by influencing the rate of translation elongation ( Hia et al, 2019 ; Hia and Takeuchi, 2021 ).…”

Structural Characterization of Trivalvaria costata Chloroplast Genome and Molecular Evolution of rps12 Gene in Magnoliids

“…After long-term development and evolution, organisms develop a certain preference for codons. The primary goals of codon usage preferences are to optimize translation yield and accuracy, protect protein structure and function, and manage resources to optimize cellular adaptation [10]. Studying codon usage patterns is an excellent way to understand biological evolution and phylogeny, as well as predict the expression and functional dynamics of unknown genes more accurately [11].…”