Different selection dynamics of S and RdRp between SARS-CoV-2 genomes with and without the dominant mutations

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) drives the ongoing COVID-19 pandemic.
• Genomic and peptide sequences are vital for developing diagnostics and therapeutics.
• Understanding viral mutation rates is critical for tracking viral evolution and fitness.

Purpose of the Study:

• To investigate the selection dynamics and mutation rates of SARS-CoV-2 genes.
• To compare these dynamics between isolates with specific common mutations (14408C>T in RdRp, 23403A>G in S gene) and those without.
• To elucidate the roles of the S gene and RdRp in viral fitness and infectivity.

Main Methods:

• Comparative genomic analysis of SARS-CoV-2 isolates.
• Analysis of mutation rates and selection pressures on specific genes (S gene, RdRp coding region).
• Stratification of isolates based on the presence or absence of key mutations (14408C>T and 23403A>G).

Main Results:

• The S gene and RdRp coding region exhibit the highest genetic variance between genotypes.
• Contrasting selection dynamics were observed: the S gene showed early positive selection followed by increasing negative selection in mutant isolates.
• The RdRp region in mutant isolates demonstrated consistent strong negative selection throughout the pandemic.

Conclusions:

• The S gene and RdRp coding region are hotspots for genetic variation in SARS-CoV-2.
• Specific mutations influence the selection pressures on these key viral genes.
• Understanding these dynamics is crucial for predicting viral evolution and informing public health strategies.