Global Assessment of Genomic Regions Required for Growth in Mycobacterium tuberculosis

PLoS Pathogens

James C. Sacchettini¹  Curtis Huttenhower²  Thomas R. Ioerger³  Yanjia J. Zhang⁴  Eric J. Rubin⁴  Christopher M. Sassetti⁵  Jarukit E. Long⁵ 

[1] Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America;Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America;Department of Computer Science, Texas A&M University, College Station, Texas, United States of America;Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America;Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America

关键词: Transposable elements;    Genomic libraries;    Mycobacterium tuberculosis;    DNA libraries;    DNA transposons;    Protein domains;    Genomic library construction;    Genetic elements;   

DOI  :  10.1371/journal.ppat.1002946

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY