Gene expression diversity among Mycobacterium tuberculosis clinical isolates

Gao, Qian; Kripke, Katharine; Saldanha, Alok J.; Wang, Yan; Holmes, Susan; Small, Peter M.

doi:10.1099/mic.0.27539-0

Cited by 81 publications

(76 citation statements)

References 38 publications

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“…Indeed, recombination between distantly positioned PE/PPE genes could bring newly recombined sequences under the control of a heterologous promoter, thus increasing the heterogeneity of expression patterns between different isolates. Such an event could explain the heterogeneity in PE/PPE expression between clinical isolates previously reported by cDNA microarray (20,51). LSP Tun5 involved a single gene, PPE54, which is one of the largest PPE genes.…”

Section: Discussionmentioning

confidence: 99%

Frequent Homologous Recombination Events in Mycobacterium tuberculosis PE/PPE Multigene Families: Potential Role in Antigenic Variability

et al. 2008

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The PE and PPE (PE/PPE) multigene families of Mycobacterium tuberculosis are particularly GC-rich and share extensive homologous repetitive sequences. We hypothesized that they may undergo homologous recombination events, a mechanism rarely described in the natural evolution of mycobacteria. To test our hypothesis, we developed a specific oligonucleotide-based microarray targeting nearly all of the PE/PPE genes, aimed at detecting signals for homologous recombination. Such a microarray has never before been reported due to the multiplicity and highly repetitive and homologous nature of these sequences. Application of the microarray to a collection of M. tuberculosis clinical isolates (n ‫؍‬ 33) representing prevalent spoligotype strain families in Tunisia allowed successful detection of six deleted genomic regions involving a total of two PE and seven PPE genes. Some of these deleted genes are known to be immunodominant or involved in virulence. The four precisely determined deletions were flanked by 400-to 500-bp stretches of nearly identical sequences lying mainly at the conserved N-terminal region of the PE/PPE genes. These highly homologous sequences thus serve as substrates to mediate both intergenic and intragenic homologous recombination events, indicating an important function in generating strain variation. Importantly, all recombination events yielded a new inframe fusion chimeric gene. Hence, homologous recombination within and between PE/PPE genes likely increased their antigenic variability, which may have profound implications in pathogenicity and/or host adaptation. The finding of high prevalence (ϳ45% and ϳ58%) for at least two of the genomic deletions suggests that they likely confer advantageous biological attributes.

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Section: Discussionmentioning

confidence: 99%

Frequent Homologous Recombination Events in Mycobacterium tuberculosis PE/PPE Multigene Families: Potential Role in Antigenic Variability

et al. 2008

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“…setClass("ZscoreEcoli",representation(pro be_id = "character", expressionmat = "matrix")) readdata.ZscoreEcoliExp<-function(xz){xa<-readLines(con = xz); tempy<-NULL;for (i in seq ( along = xa)){tempx<-unlist(strsplit(xa[i],"\t"));tempy<-c(tempy, new("ZscoreEcoli", probe_id (Gao et al, 2005). This Boolean network consists of 8 genes.…”

Section: Examining the Expression Pattern Of Genes In Clinical Strainmentioning

confidence: 99%

Biological Data Modelling and Scripting in R

Ramachandran¹,

Chaudhuri²,

Verma³

et al. 2011

Systems and Computational Biology - Bioinformatics and Computational Modeling

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“…Clinical M. tuberculosis isolates have variable gene expression profiles (25) and have different numbers of genes deleted from their chromosome (32). In animal models, M. tuberculosis appears to engender a range of immune responses and variable degrees of virulence depending on the infecting strain (5,7,47,55).…”

mentioning

confidence: 99%

Global Phylogeny ofMycobacterium tuberculosisBased on Single Nucleotide Polymorphism (SNP) Analysis: Insights into Tuberculosis Evolution, Phylogenetic Accuracy of Other DNA Fingerprinting Systems, and Recommendations for a Minimal Standard SNP Set

et al. 2006

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We analyzed a global collection of Mycobacterium tuberculosis strains using 212 single nucleotide polymorphism (SNP) markers. SNP nucleotide diversity was high (average across all SNPs, 0.19), and 96% of the SNP locus pairs were in complete linkage disequilibrium. Cluster analyses identified six deeply branching, phylogenetically distinct SNP cluster groups (SCGs) and five subgroups. The SCGs were strongly associated with the geographical origin of the M. tuberculosis samples and the birthplace of the human hosts. The most ancestral cluster (SCG-1) predominated in patients from the Indian subcontinent, while SCG-1 and another ancestral cluster (SCG-2) predominated in patients from East Asia, suggesting that M. tuberculosis first arose in the Indian subcontinent and spread worldwide through East Asia. Restricted SCG diversity and the prevalence of less ancestral SCGs in indigenous populations in Uganda and Mexico suggested a more recent introduction of M. tuberculosis into these regions. The East African Indian and Beijing spoligotypes were concordant with SCG-1 and SCG-2, respectively; X and Central Asian spoligotypes were also associated with one SCG or subgroup combination. Other clades had less consistent associations with SCGs. Mycobacterial interspersed repetitive unit (MIRU) analysis provided less robust phylogenetic information, and only 6 of the 12 MIRU microsatellite loci were highly differentiated between SCGs as measured by G ST . Finally, an algorithm was devised to identify two minimal sets of either 45 or 6 SNPs that could be used in future investigations to enable global collaborations for studies on evolution, strain differentiation, and biological differences of M. tuberculosis.Compared to many bacterial species, Mycobacterium tuberculosis harbors relatively little genetic diversity (21, 34, 37); however, there is increasing evidence that the interstrain variation that exists is biologically significant. Clinical M. tuberculosis isolates have variable gene expression profiles (25) and have different numbers of genes deleted from their chromosome (32). In animal models, M. tuberculosis appears to engender a range of immune responses and variable degrees of virulence depending on the infecting strain (5,7,47,55). In human infections, molecular epidemiological studies have suggested that certain M. tuberculosis types, identified by DNA fingerprinting, can be especially prone to drug resistance acquisition (17, 59, 65) or to global dissemination (3, 9, 27, 40, 66,

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Gene expression diversity among Mycobacterium tuberculosis clinical isolates

Cited by 81 publications

References 38 publications

Frequent Homologous Recombination Events in Mycobacterium tuberculosis PE/PPE Multigene Families: Potential Role in Antigenic Variability

Frequent Homologous Recombination Events in Mycobacterium tuberculosis PE/PPE Multigene Families: Potential Role in Antigenic Variability

Biological Data Modelling and Scripting in R

Global Phylogeny ofMycobacterium tuberculosisBased on Single Nucleotide Polymorphism (SNP) Analysis: Insights into Tuberculosis Evolution, Phylogenetic Accuracy of Other DNA Fingerprinting Systems, and Recommendations for a Minimal Standard SNP Set

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