Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases

Area of Science:

• Virology
• Molecular Biology
• Evolutionary Biology

Background:

• Middle East respiratory syndrome coronavirus (MERS-CoV) is a fatal emerging virus.
• MERS-CoV encodes two key proteases: 3C-like protease (3CLpro) and papain-like protease (PLpro).
• These proteases are crucial for processing viral polyproteins into functional nonstructural proteins.

Purpose of the Study:

• To investigate the distinct genetic and evolutionary influences on MERS-CoV 3CLpro and PLpro.
• To analyze how these influences shape protein sequence, codon usage patterns, and codon usage bias.
• To understand the functional implications of differing evolutionary pressures on these viral proteases.

Main Methods:

• Comparative analysis of MERS-CoV 3CLpro and PLpro sequences.
• Assessment of codon usage bias and nucleotide composition (AT preference).
• Application of correspondence analysis to identify genetic clusters and evolutionary influences.

Main Results:

• Both proteases show AT nucleotide preference, but differ in codon usage bias (T in PLpro, G in 3CLpro).
• Mutation pressure significantly impacts 3CLpro codon usage, while translational selection is evident in PLpro.
• PLpro is influenced by a wider range of factors (compositional, mutational) compared to 3CLpro.
• Both proteases exhibit low CpG frequencies, suggesting reduced immunogenicity.

Conclusions:

• MERS-CoV 3CLpro and PLpro are shaped by unique evolutionary trajectories.
• PLpro's complex functions (deubiquitination, immune suppression) correlate with broader evolutionary influences.
• Understanding these differences is vital for comprehending MERS-CoV replication and pathogenesis.