Mutational Patterns Cannot Explain Genome Composition: Are There Any Neutral Sites in the Genomes of Bacteria?
The GC composition of genomes is strongly correlated with second codon (GC2) and 4-fold degenerate positions (GC4) .
Second codon positions show low variability due to purifying selection on non-synonymous changes. 4-fold degenerate positions vary between 5% and 97% GC among published genomes. In the classical neutral scenario (red), 4-fold degenerate positions are nearly neutral and their composition results essentially from mutational patterns. These patterns are modified in bacteria that lose repair genes, such as mutators, which show additional AT pressure (grey area) . In the selectionist view (blue), the composition of 4-fold degenerate positions results from selection for GC content, the mutational patterns are AT-rich relative to genome composition, and there are no neutral positions. Naturally, this is an idealized view of genomes that code for many additional overlapping signals that are under selection, e.g., codon usage bias, regulatory signals, etc.