Codon Pair Bias Is a Direct Consequence of Dinucleotide Bias

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• Codon pair bias is a stable species-specific genomic characteristic.
• Recoding viral proteins with underrepresented codon pairs can attenuate viruses, but the underlying mechanisms are unclear.
• Viruses replicate within host cells, suggesting their codon usage might mirror host preferences.

Purpose of the Study:

• To investigate whether viral codon pair preferences align with host preferences.
• To explore the relationship between codon pair bias and dinucleotide bias in viruses.
• To clarify the molecular basis of virus attenuation achieved through codon pair deoptimization.

Main Methods:

• Analysis of codon pair usage in numerous human viruses.
• Comparative analysis of codon pair preferences in vertebrate, insect, and arthropod-borne viruses.
• Examination of the correlation between codon pair bias and dinucleotide bias across viral genomes.

Main Results:

• Viral codon pair preferences are only marginally influenced by host codon pair preferences.
• Arthropod-borne viruses do not preferentially use codon pairs overrepresented in arthropods.
• Codon pair bias is a direct consequence of dinucleotide bias, particularly CpG/TpA dinucleotides.

Conclusions:

• Codon pair bias does not play a significant role in encoding viral proteins.
• Virus attenuation achieved by deoptimizing codon pairs likely relies on the same molecular mechanisms as increasing CpG/TpA dinucleotides.