Inferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias.

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Codon usage bias (CUB) reflects forces like mutation and selection.
• Distinguishing selection from neutral processes, including GC-biased gene conversion (gBGC), is challenging.
• Previous methods inferred selection from CUB in highly expressed genes, with potential gBGC interference.

Purpose of the Study:

• To quantify "adaptive codon preference" as a genome-wide measure of selection on CUB.
• To investigate CUB drivers in Dictyostelium discoideum, a species lacking detectable gBGC.
• To assess the influence of expression levels and other factors on CUB.

Main Methods:

• Analysis of CUB in Dictyostelium discoideum, an AT-rich genome with no evidence of gBGC.
• Inference of neutral CUB under mutational equilibrium to define adaptive codon preference.
• Comparison of adaptive codon preference with expression-associated CUB.

Main Results:

• No evidence of gBGC was found in Dictyostelium discoideum.
• Purifying selection favors adaptive codon preference, with preferred codons being AT-rich, not GC-rich.
• Expression-associated preference partially aligns with adaptive codon preference, indicating selection beyond high expression.

Conclusions:

• Adaptive codon preference provides a robust, genome-wide measure of selection on CUB.
• Selection, not gBGC, is a primary driver of CUB in Dictyostelium discoideum.
• Factors like mRNA translation and stability influence adaptive codon preference, offering a framework for future CUB research.