Triplet-Based Codon Organization Optimizes the Impact of Synonymous Mutation on Nucleic Acid Molecular Dynamics

Area of Science:

• Molecular Biology
• Genetics
• Biophysics

Background:

• The genetic code's codon organization has nonrandom aspects not fully explained.
• The 'dual-use' codon hypothesis suggests degeneracy encodes tRNA abundance, DNA shape, and protein dynamics.

Purpose of the Study:

• Investigate the 'dual-use' codon hypothesis.
• Analyze the impact of synonymous and nonsynonymous mutations on molecular dynamics.
• Determine if the standard genetic code offers structural optimization.

Main Methods:

• Performed 7680 GPU-accelerated molecular dynamic simulations.
• Analyzed 13823 identically degenerate alternative codon reorganizations.
• Compared standard genetic code to all possible alternative assignments for aRNA and bDNA.

Main Results:

• The standard genetic code minimizes atomic fluctuations from synonymous mutations.
• It facilitates DNA polymer flexibility and resists thermostability changes.
• This optimization was more pronounced in RNA, supporting an RNA world origin.

Conclusions:

• The standard genetic code's structure likely arose from preadaptation in an RNA world.
• Dual-use codons may have enabled multiplexing of gene regulatory information.
• The code's evolution may have involved adaptive expansion from a primordial doublet code.