Evidence of bias towards buffered codons in human transcripts.

Area of Science:

• Genetics
• Molecular Biology
• Evolutionary Biology

Background:

• Codon usage bias is a known phenomenon across species, often explained by mutation-selection balance affecting translation speed and accuracy.
• Existing models link codon bias to tRNA availability and properties, focusing on translational efficiency.

Purpose of the Study:

• To explore codon usage bias from a novel perspective: selection favoring codons with higher resistance to mutation.
• To introduce and validate measures for quantifying sequence buffering capacity against mutations.

Main Methods:

• Development of two complementary metrics to calculate the average buffering capacity of genetic sequences.
• Comparative analysis of buffering capacity in human coding sequences versus random sequences and shifted reading frames.

Main Results:

• Human coding sequences demonstrate a higher buffering capacity compared to random sequences and shifted reading frames.
• Highly expressed genes exhibit significantly greater buffering capacity than non-housekeeping genes.
• This enhanced buffering in highly expressed genes aligns with their essential cellular roles (housekeeping).

Conclusions:

• Selection may favor codons that are more buffered against mutations, enhancing organismal survival by maintaining protein sequence integrity.
• Buffering capacity serves as a crucial factor in codon usage bias, particularly for essential genes.
• The findings offer a new framework for understanding the evolutionary pressures shaping codon usage.