Energy efficiency trade-offs drive nucleotide usage in transcribed regions

Area of Science:

• Genomics
• Molecular Biology
• Biophysics

Background:

• Efficient nutrient usage is a fundamental biological principle driving cellular resource allocation.
• Nucleotide synthesis constitutes a significant cellular expense, making their efficient utilization crucial for survival and replication.
• Transcribed sequences, amplified significantly, are expected to exhibit preferential usage of less expensive nucleotides.

Purpose of the Study:

• To investigate the influence of resource limitation and transcription amplification on nucleotide usage biases in prokaryotic genomes.
• To develop a theoretical model explaining observed nucleotide skews based on mutation-selection-drift equilibrium.
• To reconcile the opposing selective pressures on nucleotide usage between transcription and translation.

Main Methods:

• Development of a mutation-selection-drift equilibrium model to analyze nucleotide skews (A vs. T, G vs. C).
• Analysis of nucleotide composition across 1,550 prokaryotic genomes.
• Evaluation of the impact of codon table trade-offs on nucleotide usage at synonymous and non-synonymous sites.

Main Results:

• The derived model successfully explains nucleotide skews in prokaryotic genomes as a result of selection for efficient resource use.
• Transcription-related selection favors cheaper nucleotides (U, C) at synonymous sites.
• Unexpected trade-offs in the codon table lead to a bias towards more expensive nucleotides (A, G) at non-synonymous sites due to energetic costs of encoded amino acids.

Conclusions:

• Cellular resource efficiency drives nucleotide usage patterns, with distinct pressures acting on transcribed and translated sequences.
• The universal bias towards more expensive nucleotides at non-synonymous sites highlights complex evolutionary trade-offs between nucleotide cost and amino acid synthesis.
• Understanding these biases provides insights into genome evolution and the fundamental constraints on cellular metabolism.