Comparative analysis of Mycobacterium and related Actinomycetes yields insight into the evolution of Mycobacterium tuberculosis pathogenesis.
Comparative analysis of Mycobacterium and related Actinomycetes yields insight into the evolution of Mycobacterium tuberculosis pathogenesis.
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DOI：
10.1186/1471-2164-13-120
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发表时间：
2012-03-28
期刊：
影响因子：
4.4
通讯作者：
Galagan J
中科院分区：
文献类型：
--
作者：
McGuire AM;Weiner B;Park ST;Wapinski I;Raman S;Dolganov G;Peterson M;Riley R;Zucker J;Abeel T;White J;Sisk P;Stolte C;Koehrsen M;Yamamoto RT;Iacobelli-Martinez M;Kidd MJ;Maer AM;Schoolnik GK;Regev A;Galagan J
病原体结核分枝杆菌 (Mtb) 菌株 H37Rv 的序列已获得十多年，但对该病原体的生物学仍然知之甚少。其他结核分枝杆菌菌株和密切相关细菌的基因组序列提供了应用比较基因组学的力量来了解结核分枝杆菌发病机制进化的机会。我们使用结核病数据库 (TBDB.org) 中的 31 个基因组进行了比较分析，包括 8 种结核分枝杆菌和牛分枝杆菌、11 种其他分枝杆菌、4 种棒状杆菌、2 种链霉菌、约氏红球菌 RHA1、法西诺卡氏菌、解纤维热酸菌、类球红杆菌、痤疮丙酸杆菌和长双歧杆菌。我们的结果强调了脂质代谢及其调节的功能重要性，并揭示了与饱和和不饱和脂肪酸代谢有关的基因进化谱之间的差异。它还表明 DNA 修复和钼蝶呤辅助因子在致病性分枝杆菌中很重要。通过分析序列保守性和基因表达数据，我们鉴定了近 400 个保守的非编码区域。其中包括 37 个预测的启动子调控基序，其中 14 个对应于之前验证的基序，以及 50 个潜在的非编码 RNA，我们通过实验证实了其中 4 个的表达。我们对蛋白质进化的分析强调了与环境分枝杆菌适应专性发病机制相关的基因家族。这些家族包括脂肪酸代谢、DNA 修复和钼蝶呤生物合成。我们的分析强化了最近的发现，表明小非编码 RNA 在分枝杆菌中比之前预期的更为常见。我们的数据为在比较背景下了解 Mtb 的基因组和生物学奠定了基础，并且可以在线或通过 TBDB.org 获取。
The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.
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DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
影响因子：
6.7
作者：
Astarie-Dequeker C;Le Guyader L;Malaga W;Seaphanh FK;Chalut C;Lopez A;Guilhot C
通讯作者：
Guilhot C
影响因子：
64.5
作者：
Boshoff, HIM;Reed, MB;Mizrahi, V
通讯作者：
Mizrahi, V
影响因子：
4.4
作者：
Dzierzewicz, Z;Cwalina, B;Wilczok, T
通讯作者：
Wilczok, T
影响因子：
12.3
作者：
Anantharaman V;Aravind L
通讯作者：
Aravind L