Alleleomes characterize the survivors of 3.5 billion years of bacterial evolution

Abstract Bacteria are thought to have appeared on Earth some 3.5 billion years ago. Widespread sequencing has uncovered the set of surviving genetic alleles (termed the alleleome ) for tens of thousands of bacterial strains. Here, we characterize over 1.3 billion mutations across 54,191 sequenced genomes that define the alleleomes of 184 bacterial species. The alleleomes are surprisingly conserved, and even the most variable codons encode only a few alternate amino acids with predictably-benign consequences on protein function. Furthermore, the evolutionary stabilities of amino acids are shared across species. Lastly, the global ratio of nonsynonymous-to-synonymous mutations (dN/dS) is 0.32. Notably, human pathogens exhibit the most variation and the highest dN/dS ratios, suggesting that their genes are under increasingly positive selection. As more genome sequences become available, alleleomes provide a context to study sequence diversity across the phylogentic tree and can reveal data-driven insights into the genetic basis for natural selection in bacteria.