000172421 001__ 172421
000172421 005__ 20181203022557.0
000172421 0247_ $$2doi$$a10.1128/JB.00536-10
000172421 02470 $$2ISI$$a000281327900004
000172421 037__ $$aARTICLE
000172421 245__ $$aMassive Gene Duplication Event among Clinical Isolates of the Mycobacterium tuberculosis W/Beijing Family
000172421 269__ $$a2010
000172421 260__ $$c2010
000172421 336__ $$aJournal Articles
000172421 520__ $$aAs part of our effort to uncover the molecular basis for the phenotypic variation among clinical Mycobacterium tuberculosis isolates, we have previously reported that isolates belonging to the W/Beijing lineage constitutively overexpress the DosR-regulated transcriptional program. While generating dosR knockouts in two independent W/Beijing sublineages, we were surprised to discover that they possess two copies of dosR. This dosR amplification is part of a massive genomic duplication spanning 350 kb and encompassing >300 genes. In total, this equates to 8% of the genome being present as two copies. The presence of IS6110 elements at both ends of the region of duplication, and in the novel junction region, suggests that it arose through unequal homologous recombination of sister chromatids at the IS6110 sequences. Analysis of isolates representing the major M. tuberculosis lineages has revealed that the 350-kb duplication is restricted to the most recently evolved sublineages of the W/Beijing family. Within these isolates, the duplication is partly responsible for the constitutive dosR overexpression phenotype. Although the nature of the selection event giving rise to the duplication remains unresolved, its evolution is almost certainly the result of specific selective pressure(s) encountered inside the host. A preliminary in vitro screen has failed to reveal a role of the duplication in conferring resistance to common antitubercular drugs, a trait frequently associated with W/Beijing isolates. Nevertheless, this first description of a genetic remodeling event of this nature for M. tuberculosis further highlights the potential for the evolution of diversity in this important global pathogen.
000172421 6531_ $$aBeijing Genotype
000172421 6531_ $$aGlobal Dissemination
000172421 6531_ $$aGenomic Deletions
000172421 6531_ $$aDrug-Resistance
000172421 6531_ $$aStrains
000172421 6531_ $$aEvolution
000172421 6531_ $$aLineage
000172421 6531_ $$aDiversity
000172421 6531_ $$aAmplification
000172421 6531_ $$aPolymorphism
000172421 700__ $$aDomenech, Pilar
000172421 700__ $$aKolly, Gaelle S.
000172421 700__ $$aLeon-Solis, Lizbel
000172421 700__ $$aFallow, Ashley
000172421 700__ $$aReed, Michael B.
000172421 773__ $$j192$$tJournal Of Bacteriology$$q4562-4570
000172421 909C0 $$xU11742$$0252302$$pUPCOL
000172421 909CO $$pSV$$particle$$ooai:infoscience.tind.io:172421
000172421 917Z8 $$x164606
000172421 937__ $$aEPFL-ARTICLE-172421
000172421 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000172421 980__ $$aARTICLE