Codon equilibrium II: Its use in estimating silent-substitution rates

Area of Science:

• Molecular evolution
• Genomics
• Bioinformatics

Background:

• Eukaryotic organisms exhibit non-uniform synonymous codon usage, suggesting selective pressures.
• Understanding silent substitution rates is crucial for evolutionary and genomic analyses.

Purpose of the Study:

• To determine equilibrium-based substitution rates for synonymous codons in eukaryotes.
• To investigate the impact of incorporating divergence data on inferred selection strength.
• To estimate human-mouse divergence times using different codon set data.

Main Methods:

• Derived five equilibrium equations for silent substitution rates.
• Applied maximum entropy and man-mouse divergence data to calculate rate sets.
• Utilized simulations to validate rate calculation reliability.
• Estimated divergence times using quartet, C/T-ending duet, and A/G-ending duet codon sets.

Main Results:

• Two sets of eukaryotic codon substitution rates were determined.
• Including divergence data doubled the inferred strength of selection.
• Human-mouse divergence times varied significantly across codon sets.
• Transition rates in duet-codon sets are higher than in quartet-codon sets, particularly for A-G substitutions.

Conclusions:

• Equilibrium and divergence data provide robust methods for estimating codon substitution rates.
• Synonymous codon usage is influenced by selection, even under near-neutral conditions.
• The choice of codon sets significantly impacts evolutionary rate estimations and divergence time calculations.