Pan-Genomic Study of Mycobacterium tuberculosis Reflecting the Primary/Secondary Genes, Generality/Individuality, and the Interconversion Through Copy Number Variations

Frontiers in Microbiology

Jingfa Xiao¹  Jun Zhong²  Liya Yue²  Ju Zhang²  Guannan Ma²  Nan Ding²  Fei Chen³  Yanhong Sun⁴  Yongjie Sheng⁴  Qian Liang⁵  Hairong Huang⁵  Guirong Wang⁵  Xia Yu⁵  Xinmiao Jia⁶  Tingting Yang⁷  Cuidan Li⁷ 

[1] BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;Collaborative Innovation Center for Genetics and Development, Beijing, China;Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun, China;National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China;Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;University of Chinese Academy of Sciences, Beijing, China;

关键词: Mycobacterium tuberculosis (Mtb);    pan-genome;    core gene;    selection pressure;    adaptive evolution;    infectious disease;   

DOI  :  10.3389/fmicb.2018.01886

来源: DOAJ

【 摘 要 】

Tuberculosis (TB) has surpassed HIV as the leading infectious disease killer worldwide since 2014. The main pathogen, Mycobacterium tuberculosis (Mtb), contains ~4,000 genes that account for ~90% of the genome. However, it is still unclear which of these genes are primary/secondary, which are responsible for generality/individuality, and which interconvert during evolution. Here we utilized a pan-genomic analysis of 36 Mtb genomes to address these questions. We identified 3,679 Mtb core (i.e., primary) genes, determining their phenotypic generality (e.g., virulence, slow growth, dormancy). We also observed 1,122 dispensable and 964 strain-specific secondary genes, reflecting partially shared and lineage-/strain-specific individualities. Among which, five L2 lineage-specific genes might be related to the increased virulence of the L2 lineage. Notably, we discovered 28 Mtb “Super Core Genes” (SCGs: more than a copy in at least 90% strains), which might be of increased importance, and reflected the “super phenotype generality.” Most SCGs encode PE/PPE, virulence factors, antigens, and transposases, and have been verified as playing crucial roles in Mtb pathogenicity. Further investigation of the 28 SCGs demonstrated the interconversion among SCGs, single-copy core, dispensable, and strain-specific genes through copy number variations (CNVs) during evolution; different mutations on different copies highlight the delicate adaptive-evolution regulation amongst Mtb lineages. This reflects that the importance of genes varied through CNVs, which might be driven by selective pressure from environment/host-adaptation. In addition, compared with Mycobacterium bovis (Mbo), Mtb possesses 48 specific single core genes that partially reflect the differences between Mtb and Mbo individuality.

【 授权许可】

Unknown