Constraint on di-nucleotides by codon usage bias in bacterial genomes

Area of Science:

• Genomics
• Bioinformatics
• Molecular Evolution

Background:

• Relative dinucleotide frequency (RDF) acts as a genome signature in bacteria, showing similarity within genomes but variation between them.
• The underlying mechanisms governing RDF constancy—mutational bias versus selection—remain unclear.

Purpose of the Study:

• To comparatively analyze RDF in intergenic and coding sequences across 17 bacterial genomes with available gene expression data.
• To investigate the role of selection and codon usage bias (CUB) in shaping dinucleotide constraints within bacterial genomes.

Main Methods:

• Comparative analysis of RDF in coding and intergenic regions of 17 bacterial genomes.
• Analysis of RDF at the 2nd and 3rd codon positions in simulated coding sequences with unaltered codon usage bias (CUB).
• Comparative analysis of RDF in high expression genes (HEG) rpoB and rpoC across 199 bacteria.

Main Results:

• Dinucleotide constraint is higher in coding sequences than intergenic regions, with greater constraint at the 2nd codon position.
• Highly expressed genes (HEG) exhibit greater dinucleotide constraint at the 2nd codon position compared to low expression genes (LEG) and whole genomes.
• Simulated coding sequences show significantly lower constraint, indicating selection on CUB is crucial for observed dinucleotide constraints in HEGs.

Conclusions:

• Stronger selection on codon usage bias (CUB) in highly expressed genes drives the increased constraint on dinucleotides.
• Selection on CUB is a key factor influencing dinucleotide constraints at specific codon positions in bacterial genomes.
• This study highlights the significant role of CUB in shaping dinucleotide constraints across bacterial genomes.