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Gene expression diversity among Mycobacterium tuberculosis clinical isolates

Qian Gao^1,*,

Weihong Yan^1,

¹ Department of Medicine, Division of Infectious Disease and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305-5107, USA
² Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5307, USA
³ Statistics Department, Sequoia Hall, Stanford, CA 94305, USA

Correspondence
Peter M. Small
peters{at}gatesfoundation.org

Intraspecies genetic diversity has been demonstrated to be important in the pathogenesis and epidemiology of several pathogens, such as HIV, influenza, Helicobacter and Salmonella. It is also important to consider strain-to-strain variation when identifying drug targets and vaccine antigens and developing tools for molecular diagnostics. Here, the authors present a description of the variability in gene expression patterns among ten clinical isolates of Mycobacterium tuberculosis, plus the laboratory strains H37Rv and H37Ra, growing in liquid culture. They identified 527 genes (15 % of those tested) that are variably expressed among the isolates studied. The remaining genes were divided into three categories based on their expression levels: unexpressed (38 %), low to undetectable expression (31 %) and consistently expressed (16 %). The expression categories were compared with functional categories and three biologically interesting gene lists: genes that are deleted among clinical isolates, T-cell antigens and essential genes. There were significant associations between expression variability and the classification of genes as T-cell antigens, involved in lipid metabolism, PE/PPE, insertion sequences and phages, and deleted among clinical isolates. This survey of mRNA expression among clinical isolates of M. tuberculosis demonstrates that genes with important functions can vary in their expression levels between strains grown under identical conditions.

*These authors contributed equally to the work and the order of their names was determined by chance.

Present address: Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China.

Present address: Keck Bioinformatics User Center, UCLA, Los Angeles, CA 90095, USA.

Genes listed in Tuberculist that do not appear in our dataset, either because they are not on the microarray, or because they were removed from the dataset due to not enough good data are available in Supplementary Table S1; all genes in the data set, with expression level and functional categories in Supplementary Table S2; identity graphs, in which the log ratios from each replicate array in a set were plotted against the corresponding values from another array of the same strain, as Supplementary Figure S1; a hierarchical cluster diagram of genes as Supplementary Figure S2; a histogram of non-specific hybridization as Supplementary Figure S3 at http://mic.sgmjournals.org.

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