Evidence of selection upon genomic GC-content in bacteria

Abstract

The genomic GC-content of bacteria varies dramatically, from less than 20% to more than 70%. This variation is generally ascribed to differences in the pattern of mutation between bacteria. Here we test this hypothesis by examining patterns of synonymous polymorphism using datasets from 149 bacterial species. We find a large excess of synonymous GC→AT mutations over AT→GC mutations segregating in all but the most AT-rich bacteria, across a broad range of phylogenetically diverse species. We show that the excess of GC→AT mutations is inconsistent with mutation bias, since it would imply that most GC-rich bacteria are declining in GC-content; such a pattern would be unsustainable. We also show that the patterns are probably not due to translational selection or biased gene conversion, because optimal codons tend to be AT-rich, and the excess of GC→AT SNPs is observed in datasets with no evidence of recombination. We therefore conclude that there is selection to increase synonymous GC-content in many species. Since synonymous GC-content is highly correlated to genomic GC-content, we further conclude that there is selection on genomic base composition in many bacteria.

Figure 1. The pattern of synonymous SNPs.

The figure shows the correlation between Z, the proportion of GC↔AT SNPs that are GC→AT, and GC4, across 149 bacterial species.

Figure 2. The infinite sites assumption.

The figure shows the predicted value of Z, allowing for a violation of the infinite sites assumption, assuming that base composition is due to mutation bias alone and base composition is stationary, plotted against GC4 under the (A) constant rate and (B) exponential rate models, along with the effect of removing this bias from the observed value (Z-Z_pred) for the (C) constant and (D) exponential models.

Figure 3. The equilibrium GC content under the mutation bias model.

The figure shows the relationship between GC4_pred, the GC4 to which each species is predicted to evolve under mutation pressure, and the current GC4.

Figure 4. Translational selection.

The figure shows the relationship between GC4 for putatively highly expressed genes and GC4 for all other annotated genes. The line is for GC4_high = GC4_other.

Figure 5. Selection on GC-content.

The figure shows the effect of selection in favour of GC on Z. The relationship between Z_pred and S (2N_es) for three values of f, the equilibrium GC-content when there is no selection (i.e. the mutation bias); from top to bottom f is 0.7, 0.5 and 0.3. In these examples 2N_eμ = 0.1 and n = 10; qualitatively similar patterns are observed for other values of these two parameters.