Beyond the pan-genome: current perspectives on the functional and practical outcomes of the distributed genome hypothesis

Abstract

The principle of monoclonality with regard to bacterial infections was considered immutable prior to 30 years ago. This view, espoused by Koch for acute infections, has proven inadequate regarding chronic infections as persistence requires multiple forms of heterogeneity among the bacterial population. This understanding of bacterial plurality emerged from a synthesis of what-were-then novel technologies in molecular biology and imaging science. These technologies demonstrated that bacteria have complex life cycles, polymicrobial ecologies, and evolve in situ via the horizontal exchange of genic characters. Thus, there is an ongoing generation of diversity during infection that results in far more highly complex microbial communities than previously envisioned. This perspective is based on the fundamental tenet that the bacteria within an infecting population display genotypic diversity, including gene possession differences, which result from horizontal gene transfer mechanisms including transformation, conjugation, and transduction. This understanding is embodied in the concepts of the supragenome/pan-genome and the distributed genome hypothesis (DGH). These paradigms have fostered multiple researches in diverse areas of bacterial ecology including host-bacterial interactions covering the gamut of symbiotic relationships including mutualism, commensalism, and parasitism. With regard to the human host, within each of these symbiotic relationships all bacterial species possess attributes that contribute to colonization and persistence; those species/strains that are pathogenic also encode traits for invasion and metastases. Herein we provide an update on our understanding of bacterial plurality and discuss potential applications in diagnostics, therapeutics, and vaccinology based on perspectives provided by the DGH with regard to the evolution of pathogenicity.

Keywords: bacterial pathogenesis; comparative genomics; pan-genome.

Figure 1.. Schematic demonstrating the different types of bacterial inheritance.

(A) Bacterial cell with a single circular chromosome in blue; (B) vertical transmission from mother to daughter cells with the daughter cells being genomically identical with each other and the mother cell; (C) horizontal gene transfer methods with transferred or transferrable DNA signified by red shading: (i) transformation, foreign DNA is picked up from the environment by competent bacteria which is then recombined into the bacterial chromosome via homologous recombination; (ii) conjugation, transfers either a plasmid (episome) or chromomosonal DNA via a pilus from a ‘male’—parasitizing bacteria to a recipient; (iii) transduction, transfers foreign bacterial DNA via a phage using nonhomologous recombination.

Figure 2.. Schematic showing the relationship between the size of the core and supragenomes for different bacterial species.

The area of the inner circle for each species represents the size of the core genome relative to the supragenome which is represented by the entire area of the circle. All areas are representative of the actual percentage differences between the core and supragenomes. Starting at the lower left with Mycobacterium tuberculosis and moving clockwise through Staphylococcus aureus, Corallococcus coralloides, Escherichia coli and Pseudomonas aeruginosa the relative size of the core genome decreases compared with the supragenome.