Genome rearrangement and genetic instability in Streptomyces spp

compounds. Theseinclude numerous excreted hydrolytic enzymes, enzyme inhibitors, immunomodifiers, andover60% ofnaturally occurring antibiotics (5). Thegenome sizeis typically intherangeof5 x 103to7 x 103kilobases (kb) (19), whichissurprisingly large, being 1.5to2times thesize ofthatofEscherichia coli. Ithasa highG+C content of73 to75% (19)andsignificant levels ofbothrepetitive sequences(4to11%)and"foldback" DNA (2%). Thereisone majorgenetic linkage group whichtakestheformofa circular chromosome thatisfrequently present inmultiple copies per hyphalcompartment butispresent onlyas a single copy inthespores(25). Oneparticularly interesting aspect ofStreptomyces spp.is thephenomenon ofgenetic instability, whichmanifests itself asextraordinarily highmutation ratesaffecting certain species-specific traits. Unstable phenotypes areirreversibly lost atspontaneous frequencies ashigh as0.1%ofplated spores, butthese frequencies canbemadetoapproach 100%bythe use ofbothmutagenic (ethidium bromide andUV irradiation) andapparently nonmutagenic (cold storage) treatments (29). Themajority oftheseinstabilities are theresult of extensive chromosomal deletions which, interestingly, are frequently accompanied byintense DNA amplifications that takeplace intheabsence ofanyobvious selection pressure. Thedeletions can extend toinexcessof800kb(7), andthe physically linked amplified arrayscanextend to3,000 kb(20, 21),constituting 18and45%ofthechromosome, respectively. The lastdecadehasseen muchprogresstowards an understanding oftheseevents,reflecting theincreasing importance ofthegenus andthedevelopment ofefficient genetic systems(28) foritsmanipulation andexploitation. In thisminireview, we present an overview oftheinstability phenomenon andtheassociated chromosomal deletion and amplification events, withparticular reference toone ofthe best-characterized systems, S.glaucescens.