Streptomyces are filamentous bacteria that produce more than two-thirds of known antibiotics. Due to their multicellular lifestyle as well as their prolific production of secondary metabolites, Str...Show moreStreptomyces are filamentous bacteria that produce more than two-thirds of known antibiotics. Due to their multicellular lifestyle as well as their prolific production of secondary metabolites, Streptomyces are of unique fundamental and applied importance. However, Streptomyces have unstable genomes, an attribute that can cause genomic rearrangements and dramatically alter their phenotype. Previous studies have failed to explain this phenomenon. In this dissertation, we investigate the evolutionary functions and mechanisms of genomic instability in Streptomyces coelicolor. We first find that a subpopulation of cells generated through large genomic rearrangements becomes specialized to produce antibiotics. This results in a division of labor which benefits the entire colony, while the yield and diversity of antibiotics are maximized, despite significant fitness costs to this altruistic subpopulation. Next, we show that these altruistic mutants continue to lose fitness due to the irreversible accumulation of large deletions and deleterious mutations, coupled to an increased mutation rate. Finally, we explore the molecular consequences of large genomic rearrangements for development and antibiotic production using detailed proteomics and metabolomics analyses, which highlight key pathways that are impacted by these genomic events. Overall, this dissertation provides new insights of genomic instability in Streptomyces. Show less
