| Actinomycetes contribute key pharmaceuticals to the health care industry. This research aimed, originally, to identify strains of S. coelicolor , a model actinomycete, that synthesize larger amounts of a native antibiotic, the blue-pigment actinorhodin. A high-throughput screen of thousands of transposon mutants identified, instead, several tens of mutants that sustained several types of gross rearrangements to the linear chromosome. We subsequently identified similar rearrangements in a wild-type library. We characterized these rearrangements, which deleted and amplified hundreds of S. coelicolor genes, and identified a critical role of native insertion elements, together with homologous and nonhomologous recombination, during a phenomenon called genetic instability. Despite the discovery of genetic instability more than two decades ago, the underlying mechanisms remain poorly understood. This research revealed (1) an altered pattern of circular chromosomes when S. coelicolor harbors a foreign transposon, S. fradiae Tn4560; (2) the replacement of the left arm of the chromosome, when it suffers a large deletion, by the right chromosome arm; (3) a spontaneous amplification of a large region inside the chromosome, likely an ancient mobile element, that encompasses the entire gene cluster of actinorhodin; and (4) a duplication of nearly half the chromosome (4.1 Mb) that increases the genome size by 50%. We suggest how chromosomes of bacteria evolve in nature and how gross genetic changes might occur during industrial processes such as fermentations and strain improvement programs. |
