title: Global assessment of genomic regions required for growth in Mycobacterium tuberculosis.
abstract: Identifying genomic elements required for viability is central to our understanding of the basic physiology of bacterial pathogens. Recently, the combination of high-density mutagenesis and deep sequencing has allowed for the identification of required and conditionally required genes in many bacteria. Genes, however, make up only a part of the complex genomes of important bacterial pathogens. Here, we use an unbiased analysis to comprehensively identify genomic regions, including genes, domains, and intergenic elements, required for the optimal growth of Mycobacterium tuberculosis, a major global health pathogen. We found that several proteins jointly contain both domains required for optimal growth and domains that are dispensable. In addition, many non-coding regions, including regulatory elements and non-coding RNAs, are critical for mycobacterial growth. Our analysis shows that the genetic requirements for growth are more complex than can be appreciated using gene-centric analysis.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Yanjia J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ioerger
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.forename: Jarukit E
authors.initials: JE
authors.lastname: Long
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Sassetti
authors.forename: James C
authors.initials: JC
authors.lastname: Sacchettini
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rubin
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D020869:Gene Expression Profiling; D016678:Genome; D016680:Genome, Bacterial; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
chemical_list: D001426:Bacterial Proteins; D022661:RNA, Untranslated