Genomic Legacies of Ancient Adaptation Illuminate GC-Content Evolution in Bacteria

Bacterial evolution is characterized by strong purifying selection as well as rapid adaptive evolution in changing environments. In this context, the genomic GC content (genomic GC) varies greatly but presents some level of phylogenetic stability, making it challenging to explain based on current hypotheses. To illuminate the evolutionary mechanisms of the genomic GC, we analyzed the base composition and functional inventory of 11,083 representative genomes. A phylogenetically constrained bimodal distribution of the genomic GC, which mainly originated from parallel divergences in the early evolution, was demonstrated. Such variation of the genomic GC can be well explained by DNA replication and repair (DRR), in which multiple pathways correlate with the genomic GC. Furthermore, the biased conservation of various stress-related genes, especially the DRR-related ones, implies distinct adaptive processes in the ancestral lineages of high- or low-GC clades which are likely induced by major environmental changes. Our findings support that the mutational biases resulting from these legacies of ancient adaptation have changed the course of adaptive evolution and generated great variation in the genomic GC. This highlights the importance of indirect effects of natural selection, which indicates a new model for bacterial evolution. IMPORTANCE GC content has been shown to be an important factor in microbial ecology and evolution, and the genomic GC of bacteria can be characterized by great intergenomic heterogeneity, high intragenomic homogeneity, and strong phylogenetic inertia, as well as being associated with the environment. Current hypotheses concerning direct selection or mutational biases cannot well explain these features simultaneously. Our findings of the genomic GC showing that ancient adaptations have transformed the DRR system and that the resulting mutational biases further contributed to a bimodal distribution of it offer a more reasonable scenario for the mechanism. This would imply that, when thinking about the evolution of life, diverse processes of adaptation exist, and combined effects of natural selection should be considered.