Human SARS-CoV-2 has evolved to reduce CG dinucleotide in its open reading frames.

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• COVID-19, caused by SARS-CoV-2, poses a significant global health threat.
• Understanding viral genome composition is crucial for comprehending viral replication and pathogenesis.

Purpose of the Study:

• To investigate the CG dinucleotide abundance in the SARS-CoV-2 genome.
• To elucidate the mechanisms and implications of CG reduction in SARS-CoV-2.

Main Methods:

• Bioinformatic analysis of the SARS-CoV-2 genome.
• Comparative genomic analysis with cellular organisms.

Main Results:

• SARS-CoV-2 demonstrates extremely low CG dinucleotide abundance in its open reading frames.
• CG reduction is primarily driven by C/G to A/T mutations, with CG being the preferred target.
• The 5'-untranslated region of SARS-CoV-2 has high CG content and can form an internal ribosome entry site (IRES) for host ribosome recruitment.
• Low CG content facilitates efficient viral RNA translation by minimizing energy expenditure for disrupting genomic RNA stem-loops.
• Cellular organism genomes also exhibit low CG abundance, suggesting a universal mutation pattern.

Conclusions:

• The genomic composition of SARS-CoV-2, particularly its low CG abundance and IRES capability, contributes to efficient viral replication.
• The universal C/G to A/T mutation pattern across life forms warrants further investigation into its evolutionary and functional significance.
• The association of CG dinucleotides with CpG islands, mutational hotspots, and SNPs in cellular organisms requires deeper exploration.