麻风分枝杆菌基因组1.5兆碱基的多重测序。

Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.

作者信息

Smith D R, Richterich P, Rubenfield M, Rice P W, Butler C, Lee H M, Kirst S, Gundersen K, Abendschan K, Xu Q, Chung M, Deloughery C, Aldredge T, Maher J, Lundstrom R, Tulig C, Falls K, Imrich J, Torrey D, Engelstein M, Breton G, Madan D, Nietupski R, Seitz B, Connelly S, McDougall S, Safer H, Gibson R, Doucette-Stamm L, Eiglmeier K, Bergh S, Cole S T, Robison K, Richterich L, Johnson J, Church G M, Mao J I

机构信息

Genome Therapeutics Corporation, Collaborative Research Division, Waltham, Massachusetts 02154, USA.

出版信息

Genome Res. 1997 Aug;7(8):802-19. doi: 10.1101/gr.7.8.802.

DOI:10.1101/gr.7.8.802

PMID:9267804

Abstract

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.

摘要

利用计算机辅助多重测序技术测定了麻风分枝杆菌1.5 Mb基因组DNA的核苷酸序列。这使得2.8 Mb的麻风分枝杆菌基因组序列完成度达到了约66%。这些序列来自43个重组黏粒，包含1046个推定的蛋白质编码基因、44个重复区域、3个tRNA和15个tRNA。每1.4 kb有一个基因的基因密度略低于支原体（每1.2 kb一个基因）。在蛋白质编码基因中，44%与功能明确的基因有显著匹配。对1157个麻风分枝杆菌蛋白和1564个结核分枝杆菌蛋白的比较显示，同源基因组块呈现复杂的镶嵌模式，在保守的图谱顺序中有多达22个相邻蛋白。与已知的酶、抗原、膜、细胞壁、细胞分裂、多药耐药和毒力蛋白的匹配提示了治疗和疫苗靶点。麻风分枝杆菌基因组的异常特征包括大型聚酮合酶（pks）操纵子、内含肽和高度碎片化的假基因。