Theoretical minimal RNA rings designed according to coding constraints mimic deamination gradients

Area of Science:

• Molecular Biology
• Genetics
• Evolutionary Biology

Background:

• Deaminations (A->G, C->T) are spontaneous mutations increasing with DNA single-strandedness.
• These mutations can create genomic mutational and nucleotide frequency gradients.
• Gene positioning may evolve to avoid deamination, impacting codon positions.

Purpose of the Study:

• To investigate deamination gradients in theoretical minimal RNA rings simulating prebiotic RNAs.
• To explore the relationship between RNA structure, coding properties, and deamination patterns.
• To understand how the genetic code might influence early RNA evolution and mutation avoidance.

Main Methods:

• Simulated 22-nucleotide RNA rings with start/stop and single amino acid codons.
• Designed RNA rings to form stem-loop structures, mimicking tRNA-like features.
• Analyzed deamination gradients within these theoretical RNA rings based on their sequence and coding potential.

Main Results:

• Deamination gradients were observed in RNA rings even without explicit design for them.
• Homology with transfer RNAs (tRNAs) provided stronger evidence for deamination gradients than coding properties alone.
• Gradients initiated at predicted anticodons, correlating with early amino acid integration into the genetic code.

Conclusions:

• The universal genetic code dictates nucleotide deamination gradients in minimal RNA rings.
• These findings suggest evolutionary adaptations to mitigate deamination mutation consequences.
• The genetic code's structure likely influenced the evolution of tRNAs, synthetases, and polymerases.