Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved

被引:517
作者
Comas, Inaki [2 ]
Chakravartti, Jaidip [1 ]
Small, Peter M. [3 ,4 ]
Galagan, James [5 ,6 ]
Niemann, Stefan [7 ]
Kremer, Kristin [8 ]
Ernst, Joel D. [1 ]
Gagneux, Sebastien [2 ,9 ,10 ]
机构
[1] NYU, Sch Med, New York, NY 10016 USA
[2] Natl Inst Med Res, MRC, London NW7 1AA, England
[3] Inst Syst Biol, Seattle, WA USA
[4] Bill & Melinda Gates Fdn, Seattle, WA USA
[5] MIT, Broad Inst, Cambridge, MA 02139 USA
[6] Harvard Univ, Cambridge, MA 02138 USA
[7] Res Ctr Borstel, Borstel, Germany
[8] Natl Inst Publ Hlth & Environm, Mycobacteria Reference Lab CIb LIS, NL-3720 BA Bilthoven, Netherlands
[9] Swiss Trop & Publ Hlth Inst, Basel, Switzerland
[10] Univ Basel, Basel, Switzerland
基金
美国国家卫生研究院; 瑞士国家科学基金会; 英国医学研究理事会;
关键词
HUMAN-IMMUNODEFICIENCY-VIRUS; GENOME VARIATION; VACCINE; PATHOGENS; SEQUENCE; INSIGHTS; STRAINS; GENES; HIV-1; BCG;
D O I
10.1038/ng.590
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mycobacterium tuberculosis is an obligate human pathogen capable of persisting in individual hosts for decades. We sequenced the genomes of 21 strains representative of the global diversity and six major lineages of the M. tuberculosis complex (MTBC) at 40- to 90-fold coverage using Illumina next-generation DNA sequencing. We constructed a genome-wide phylogeny based on these genome sequences. Comparative analyses of the sequences showed, as expected, that essential genes in MTBC were more evolutionarily conserved than nonessential genes. Notably, however, most of the 491 experimentally confirmed human T cell epitopes showed little sequence variation and had a lower ratio of nonsynonymous to synonymous changes than seen in essential and nonessential genes. We confirmed these findings in an additional data set consisting of 16 antigens in 99 MTBC strains. These findings are consistent with strong purifying selection acting on these epitopes, implying that MTBC might benefit from recognition by human T cells.
引用
收藏
页码:498 / U41
页数:8
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