Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
BMC Genomics. 2012 Mar 28;13:120. doi: 10.1186/1471-2164-13-120.
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.
病原体结核分枝杆菌（Mtb）菌株 H37Rv 的序列已经有十多年的历史了，但病原体的生物学仍然知之甚少。来自其他 Mtb 菌株和密切相关细菌的基因组序列提供了一个机会，可以应用比较基因组学的力量来了解 Mtb 发病机制的演变。我们利用来自结核病数据库（TBDB.org）的 31 个基因组进行了比较分析，包括 8 株 Mtb 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、Rhodococcus jostii RHA1、Nocardia farcinia、Acidothermus cellulolyticus、Rhodobacter sphaeroides、Propionibacterium acnes 和 Bifidobacterium longum。
我们的结果突出了脂质代谢及其调控的功能重要性，并揭示了参与饱和和不饱和脂肪酸代谢的基因进化特征之间的差异。这也表明 DNA 修复和钼辅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。其中包括 37 个预测的启动子调控基序，其中 14 个对应于先前验证的基序，以及 50 个潜在的非编码 RNA，其中我们实验证实了 4 个的表达。
我们对蛋白质进化的分析突出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 修复和钼辅因子生物合成。我们的分析加强了最近的发现，表明小非编码 RNA 在分枝杆菌中比以前预期的更为普遍。我们的数据为在比较背景下理解 Mtb 的基因组和生物学提供了基础，并可在线获取和通过 TBDB.org 获得。
