On the biased nucleotide composition of the human coronavirus RNA genome

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• Coronaviruses (CoVs) possess a single-stranded RNA genome.
• Previous studies noted general nucleotide biases in CoVs, such as high uracil (U) and low cytosine (C) content.
• The functional significance of these nucleotide biases remains largely unexplored.

Purpose of the Study:

• To investigate the nucleotide composition of the RNA genome across six human coronavirus species.
• To identify species-specific nucleotide signatures and their variability.
• To explore the potential biological function and evolutionary implications of observed nucleotide biases.

Main Methods:

• Comparative analysis of RNA genome sequences from six human coronavirus species.
• Quantification of nucleotide frequencies (A, U, G, C) for each isolate.
• Correlation analysis to assess relationships between nucleotide proportions, particularly U and C.
• Examination of nucleotide bias distribution within structured and unstructured regions of the viral RNA.

Main Results:

• General coronavirus nucleotide biases (high U, low C) were confirmed, but significant species-specific variations were detected.
• A striking inverse relationship between uracil (U) and cytosine (C) proportions was observed, acting as communicating vessels (U: 30.7%-40.3%, C: 20.0%-12.9%).
• Nucleotide biases were more pronounced in unpaired RNA regions, suggesting potential functional relevance.

Conclusions:

• The variable and inversely correlated nucleotide biases in human coronaviruses, particularly U and C, represent a distinct signature.
• These atypical nucleotide biases are proposed to be the direct cause of characteristic codon usage in coronaviruses.
• The findings have implications for understanding the evolution of human coronaviruses, including novel pathogens like MERS and SARS.