Similar compositional biases are caused by very different mutational effects.

Area of Science:

• Genomics
• Molecular Evolution
• Bioinformatics

Background:

• Compositional replication strand bias (GC skew) is a common feature in diverse genomes.
• Cytosine deamination (C-->T) is often cited as the primary cause, but its exact role and other mutational influences remain unclear.
• It is unknown if mutational asymmetries are conserved across species, stable over time, or near equilibrium.

Purpose of the Study:

• To investigate the contributions of various substitution types to GC skew.
• To determine if mutational asymmetries are conserved across bacterial taxa.
• To assess if genomes are at mutational equilibrium.

Main Methods:

• Analysis of nearly neutral sites in bacterial genomes.
• Inference of substitution spectra at fourfold degenerate positions in non-highly expressed genes.
• Application of a bootstrap procedure to identify replication-associated compositional biases and asymmetries.

Main Results:

• All analyzed taxa exhibit an overrepresentation of G over C on the leading strand, with notable A/T imbalances.
• Significant substitution asymmetries were observed, but varied widely among taxa; no single substitution type was universally biased.
• In highly biased genomes, A-->G substitutions, not C-->T, were the dominant factor shaping compositional bias.

Conclusions:

• Replication strand bias is a multifactorial process with varying mutational underpinnings across different genomes.
• Most genomes are not at compositional equilibrium, indicating deep imprints of mutational heterotachy.
• Observed compositional biases do not necessarily reflect similar underlying mutational processes, necessitating caution in interpretation.