Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Codon usage variations in mammals are debated regarding their role in fine-tuning mRNA translation.
• Recent studies suggest Gene Ontological (GO) pathways may regulate protein production via codon and anticodon pool modifications.

Purpose of the Study:

• To investigate whether codon usage variations in mammalian genes impact mRNA translation efficiency.
• To determine the underlying mechanisms driving codon usage differences in mammalian transcriptomes.

Main Methods:

• Comparative analysis of gene sequence content within specific GO categories against the exonic genome background.
• Quantification of translational efficiency in healthy and cancerous human and mouse tissues.

Main Results:

• While random sampling explains some codon usage variability, nearly half of GO sets exhibited more variation than expected.
• Translational efficiency remained stable across different mRNA sets, regardless of cell-type specificity, with a given tRNA pool.
• The disconnect between codon usage variation and stable translational efficiency is attributed to GC content differences between gene sets.

Conclusions:

• Codon usage differences in mammalian transcriptomes are primarily driven by mutational biases, such as GC content variations resulting from genome repair and duplication.
• Selective pressures from codon-driven translational rates are unlikely to be the main driver of codon usage differences in mammals.