Codon selection reduces GC content bias in nucleic acids encoding for intrinsically disordered proteins.

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Protein-coding nucleic acids display distinct compositional and codon biases between intrinsically disordered regions (IDRs) and structured regions.
• Previous studies, mainly in Eukaryota, linked elevated GC content in IDR-encoding sequences to biased amino acid composition.

Purpose of the Study:

• To investigate GC content bias in IDR-encoding regions across Eukaryota, Archaea, and Bacteria.
• To determine if GC content bias is solely due to amino acid composition or if other factors are involved.
• To identify compensatory codon selection mechanisms influencing GC content in IDRs.

Main Methods:

• Analysis of GC content in IDR-encoding regions from 44 species across all three domains of life.
• Comparison of observed GC content bias with predictions based on amino acid composition.
• Empirical investigation of codon usage bias and its relationship with overall organismal GC content.

Main Results:

• Regions encoding IDRs consistently exhibit significantly elevated GC content across all domains of life.
• This elevated GC content is largely due to amino acid composition but shows a bias independent of overall GC content.
• Compensatory selection for AT-rich codons was observed, reducing GC content bias in IDRs, and this selection is dependent on the organism's overall GC content.

Conclusions:

• GC content bias in IDR-encoding regions is a conserved phenomenon across life, influenced by both amino acid composition and compensatory codon selection.
• The observed codon selection is AT-rich and organismal GC content-dependent, suggesting a complex interplay of evolutionary forces.
• Further research is needed to ascertain whether these biases are causal or symptomatic of other underlying biological drivers.