Increased Mutation Rate is Linked to Genome Reduction in Prokaryotes

The evolutionary processes that drive variation in genome size across the tree of life remain unresolved. Effective population size (Ne) is thought to play an important role in shaping genome size, a key example being the reduced genomes of insect endosymbionts, which undergo population bottlenecks during transmission. However, the existence of reduced genomes in marine and terrestrial prokaryote species with large Ne demand an alternative explanation. One such alternative is enhanced mutation rate, which might increase an organism’s ability to adapt to novel environments, but might also promote gene loss. We employed a novel approach involving molecular evolutionary and phylogenomic analyses of nine lineages of prokaryotes that display various levels of genome reduction: Blattabacterium and Buchnera insect endosymbionts, marine Prochlorococcus and Synechococcus, the thermophilic archaean Thermococcus, and five lineages of free-living bacteria belonging to the Proteobacteria, Actinobacteria, and Bacteroidetes. We found that rates of gene loss strongly correlate with mutation rates in all of these groups, with the exception of two lineages of free-living bacteria, and show weak or no correlation with the ratio of nonsynonymous/synonymous substitution rates (dN/dS). This indicates that genome reduction is largely associated with increased mutation rate, while the association between gene loss and changes in Ne is less well defined. Lineages with relatively high dS and dN, as well as smaller genomes, lacked multiple DNA repair genes, providing a proximate cause for increased mutation rates. Our findings suggest that similar underlying mechanisms drive genome reduction in both intracellular and free-living prokaryotes, with implications for developing a comprehensive theory of prokaryote genome size evolution.