Selection on synonymous codons in mammalian rhodopsins: a possible role in optimizing translational processes

Area of Science:

• Evolutionary biology
• Genetics
• Molecular biology

Background:

• Synonymous codon usage influences gene expression, affecting translation, mRNA stability, and splicing.
• Highly expressed genes typically show stronger selection on codon usage, even in mammals.
• Rhodopsin, crucial for vision, is a highly expressed gene in vertebrates.

Purpose of the Study:

• To investigate codon usage bias patterns in mammalian rhodopsin sequences.
• To infer selection pressures on translational mechanisms like elongation, folding, mRNA stability, and splicing.
• To differentiate synonymous codon selection from mutational effects in a highly expressed gene.

Main Methods:

• Phylogenetic codon-based likelihood models were used to analyze 18 mammalian rhodopsin sequences.
• Mutation-selection models were applied to identify evidence of selection at synonymous sites.
• Codon usage bias was compared between different protein regions (loops vs. helices) and mRNA structures (paired sites, ESE regions).

Main Results:

• Significant evidence for selection at synonymous sites was found, with C-ending codons showing high relative fitness and abundance at conserved sites.
• Codon usage bias differed between rhodopsin loops and helices.
• GC-ending codons were more prevalent at paired mRNA sites, and lower synonymous mutation rates were observed in exonic splicing enhancer (ESE) regions.

Conclusions:

• Codon bias in mammalian rhodopsin balances translational speed, accuracy, and protein folding, particularly in complex regions.
• Selection at synonymous sites may enhance mRNA stability and splicing efficiency in ESE regions.
• Studying highly expressed genes phylogenetically is crucial for understanding synonymous substitution evolution.