The bacterial guide to designing a diversified gene portfolio

Abstract

The stunning ability of bacteria to evolve and adapt has contributed to the success of these single cells, which have inhabited the Earth for billions of years and play vital roles in the environment and in human health. The goal of this chapter is to present and discuss the population-level organizational scheme of bacterial pangenomes, wherein genes are distributed among the strains of a species, such that each individual strain encodes only a subset of the genes available at the population level. Genes from the accessory/distributed genome (those present only in a subset of strains within a species) impart diverse functions or variations on a conserved function to strains. Moreover, horizontal gene transfer generates novel gene combinations. The maintenance and spread of any given gene arrangement are influenced by fitness. Further, the extent of genomic plasticity is regulated by restriction modification systems, phage-defense systems, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated proteins (CRISPRCas). The combination of a pangenome structure and genomic plasticity reveals a successful strategy for bacterial adaptation to ever-changing environments. From a clinical perspective, pangenome analyses inform the selection of therapeutic targets, designed to focus either on an entire species or on virulence features within a species. Further, they provide a framework for modeling the efficacy of drugs and vaccines. In summary, following the explosion in sequencing technology, pangenome studies have revealed remarkable genomic organizations at the levels of species, with important implications to our understanding of evolution, and our ability to design therapeutics and predict their long-term outcomes.