摘要
基因组学的发展已经经历了近二十年的历史。随着新测序方法的出现,大大加快了基因组测序的步伐。如何处理和分析这些基因组数据成为基因组学研究中的主要困难。
本论文建立的两种全新的生物信息学方法均能够大大加快比较基因组学的工作速度,并且得到更准确的分析结果。以这两个方法为主要工具,结合其他功能基因组和比较基因组学方法,本论文对8个细菌基因组进行了生物信息学分析,并且发现其各自的重要特性。
通过这些方法的建立和研究的进行,我们能够进一步加深对微生物的理解,特别是加深对微生物遗传信息的了解,并且极大促进相关分子生物学的生理生化特性的研究工作。
Ⅰ
随着高通量测序法的发展,基因组的数量急剧膨胀,使比较基因组学成为后基因组时代的研究热点。比较基因组学通过比较全基因组序列来分析生物之间进化关系,遗传差异和潜在表型差异。直系同源基因的寻找是比较基因组学的基础问题,为比较基因组学的后续工作提供基础。直系同源基因寻找程序主要分为基于BLAST的方法和基于进化树重建的方法,但是现有的所有直系同源基因寻找程序都依赖于原有的注释。
本论文选取大肠杆菌种和古菌界的完整基因组序列为研究材料,设计了全新的基于基因与基因组比较的直系同源基因寻找程序。这个程序使用BLAST方法进行基因预测,并使用Inparanoid方法将基因比较为直系同源基因对,最后使用MCL程序将基因对进一步聚类,形成直系同源基因群。
程序突破了直系同源基因寻找依赖于原有注释的瓶颈,在大肠杆菌和古菌中发现了比原来更多的核心基因群,并重建了两个种属的进化树,同时发现在大肠杆菌中有显著的基因消减现象。
Ⅱ
比较基因组学的一个关键问题是对生物的进化关系的重建。分子遗传学中重建进化树的基础是生物DNA或氨基酸序列上的碱基改变。突变是造成这种碱基改变的一个重要原因,突变随着时间经过而发生,从而形成进化中的树状结构；然而,同源重组也是导致碱基改变的一个重要原因。同源重组用一个异源的片段替换基因组的原本片段,从而在短时间内引入大量的碱基改变。重组可以在远源的物种之间发生,从而打乱生物的树状进化结构。这两种造成碱基改变的方式通常难以区分,但是对进化树重建有重要影响。
本论文中引入泊松分布模型来描述随机突变,并通过统计学方式初步区分重组与突变。为了确定重组影响的程度和范围,我们还是用独创的MaxFisher方式对相邻片段间的碱基分布进行区分,进而将基因组区分为重组区和突变区。
使用区分后的突变,可以进行进化树重建,得到更加准确的进化结果。同时,论文中发现,重组不但可以影响进化树的枝长,从而误导进化分子钟的推算,还可以直接影响进化树的拓扑结构,从而使我们无法得到真正的物种亲缘关系。
Ⅲ
极端嗜酸的甲烷氧化细菌Methylacidiphilum inferorum V4可以在极端酸性的地裂环境中降解地壳喷发的甲烷,降低温室气体的排放。极端酸性的地裂环境中每年释放大量的甲烷,然而先前的研究中,使用通用引物无法在酸性环境下发现甲烷氧化细菌。目前已知的甲烷氧化细菌都属于原细菌门,最低生长PH值仅为4.0。
本论文中描述了一个极端嗜酸的甲烷氧化细菌Methylacidiphilum inferorum V4,并使用全基因组测序方法取得了V4的全基因组序列。
与原有的甲烷氧化细菌不同,V4属于疣微菌门,并且可以在2.0-2.5的pH值下生长。本研究在甲烷氧化细菌Methylacidiphilum inferorum V4的基因组中发现了独特的甲烷氧化途径,并分析了V4的核心代谢和其他重要功能途径,并且在全基因组中发现大量的横向转移事件。
Ⅳ
目前已进行的大肠杆菌基因组研究缺乏对具有亲缘关系的克隆之间的详尽遗传改变的研究。大肠杆菌O157：H7是重要的肠出血型致病大肠杆菌,它在世界范围内造成过多次大流行,而与它亲缘关系最近的O55：H7属于另一个致病类型,这两者之间的特性差异是由于基因组上的遗传改变造成。
本论文中完成了对一株O55：H7菌株的全基因组测序,并且将它与两个O157：H7菌株进行基因组学和蛋白质组学水平的比较。本论文对它们之间的包括突变,重组和横向基因转移等大多数遗传差异都进行了定位,并使用同义突变来对它们的分化时间做出了估计。作为参照,我们还研究了3株密切联系的肠外致病大肠杆菌基因组。
O55：H7和O157：H7的主要差别包括一个导致O抗原变换的重组区域。此外,O55：H7中有一个特异的二型分泌系统,而O157：H7中则有更多的三型分泌系统作用因子。他们之间噬菌体也发生了很大的改变。如果使用之前在霍乱弧菌中的进化速率,O55：H7和O157：H7分化时间大约为400年前,如果使用传统分子钟,分化时间大约为14,000到70,000年左右。通过肠外致病大肠杆菌簇的验证,本研究发现大肠杆菌中重组频率比霍乱弧菌中要低。
V
大肠杆菌标准菌株K-12菌株MC4100是最常用的实验室菌株之一。在80年代使用冻干保存之前,K-12菌株在世界各地的实验室中经过了长期的传代过程,其中包括大量记录的和未被记录的遗传改变。这些改变使不同的K-12菌株之间遗传背景出现差异,并导致了全局调控和表型的差异。
本研究对大肠杆菌K-12菌株MC4100进行了全基因组测序,并将其与其它3株已测序的K-12菌株进行比较。在所有已测序K-12菌株内部发现了193个特异的点突变以及许多插入和缺失事件。
通过将这些点突变和插入缺失事件关联,可以解释许多K-12菌株之间的表型差异,然而还有很多点突变的功能未知。这些遗传改变中的大部分都不是人工操作的结果,而是随机的遗传改变。这些变异说明即使在实验室环境中,也需要考虑遗传背景差异带来的潜在实验差异。
Ⅵ
物种进化的多态性是进化中的一个关键问题。传统认为这种多态性是由于环境中复杂的选择压力造成。然而最新的研究证明,即使在单一的选择压力环境下,物种也倾向于通过多种不同的方式适应环境。
本论文通过对大肠杆菌MC4100在同一实验室恒化条件下产生的5个子代进行全基因组测序和蛋白质组学研究,深入解析由磷限制带来的遗传改变,发现细菌通过以rpoS为核心的调控基因的改变来增强对环境的适应能力。
经过一个月左右的进化,MC4100单一菌株的子代出现了显著的分化。进行测序的5个子代通过对不同调控基因的突变改变了自身的环境适应能力。本论文通过这一实验说明细菌在单一选择压力下可以通过不同的调控基因改变来适应环境。
There have been about twenty years since the emergency of the genomics. More and more genomes were sequenced after the application of new generation sequencing method in 2004. How to deal with these massive genomic data becomes the most important problem in the post-genomic researches.
Both of the two new bioinformatic methods in this work can greatly improve the comparative genomic analysis. Using these methods, together with other functional and comparative genomics methods, we analyzed 8 bacterial genomes and deduced the evolution and charatistic of them.
Due to these methods and researches, we improved our knowledges, especially on the genetic nature of micro-organisms.
Ⅰ
Due to the development of high-throughput sequencing and the explosion of completed genomes, comparative genomics becomes more and more important at the post-genomic Era. Comparative genomics compares the genomes from different organisms to re-construct their phylogenic relationships and differences in genotypes, as well as the potential changes in phenotypes. The detection of orthologs is the basis of comparative genomics and other further researches. However, all the present methods for the detection of orthologs are based on the given annotations, which are full of errors.
Using the Escherichia coli and archaea, we designed a new ortholog detect method that compares genes against genomes directly. We apply tblastn to predict putative homologs, use Inparanoid to generate ortholog pairs, and finally cluster the pairs and generate the ortholog groups using MCL method.
This method does not need original annotation and can find much larger core-genomes in both E. coli and archaea. The phylogenic relationships of both of the species were re-build and gene contraction was found in E. coli.
Ⅱ
A key problem in comparative genomics is to rebuild the phylogenic relationships. The basis of the phylogenetic analysis is the base changes in the DNA or amino acid sequences. Mutation is one of the important power to cause base changes and lead to a tree-like structure in the evolution of an organism. However, recombination can bring in foreign fragments that carry many base changes in a very short time. These two types of base changes can not be easily identified and will interrupt our phylogenetic analysis.
The Poisson model was imported to describe the random mutations in this part. Then the recombinations and mutations can be identified using statistic method. The MaxFisher method was adopted to verify the bounders and differ the genome to be alternative recombinant or mutational blocks.
We can rebuild the tree phylogenetic relationships using the mutations. We found the recombinations affect not only the branch length, but also the topology of the tree.
Ⅲ
Methylacidiphilum inferorum V4 can oxidation methane in the extremely acidophilic environment of the geothermal area, from which tons of methane was emitted per year. Previous researches have failed to detect any methanotroph in the extremely acidophilic geothermal area and all known methanotrophs have a lower limit of pH 4.0.
We isolated and sequenced the genome of Methylacidiphilum inferorum V4, which can ultilize methane at a low pH of 2.0-2.5, and found a new pathway involved in methanotrophy. We also analyzed the central metabolic pathway and some other important pathways, and found that the genome of V4 was constructed by many LGT events.
IV
There have been no genome studies of closely related clones which aimed at exposing the details of evolutionary change in evolution. E. coli O157:H7 is important EHEC that cause epidemics over the world. It is most related to 055:H7, which belongs to another pathogenic type of E. coli. The differences of the characteristic in these two lineages are caused by genetics differences in their genomes.
We sequenced an 055:H7 strain and compared it to 2 completed O157:H7 genomes based on proteomics and bioinformatics results. We were able to allocate most of the genetic changes, including indels, mutations and recombinations, to different lineages. We estimated their divergence time based on the synonymous mutations. We also explored the recombination rate in 3 closely related ExPEC strains.
The major difference between O55:H7 and 0157:117 is the recombinational event that shifts the O-antigen. Other than that, a unique T2SS is present in the chromosome of O55:H7. There are more T3SS effectors in O157:H7 than in O55:H7. The prophages in their chromosomes are greatly changed, as well. They were thought to be diverged within 400 years if we calculated based on the mutation rate from our previous researches on Vibrio cholerae. And the divergence time is 14k to 70k years if we using traditional mutation rate.
V
The E. coli K-12 strain MC4100 is one of the mostly used type strains in the labs. The K-12 strains are kept on plates and many record or unknown genetic changes occur until the 1980s, from when the lyophilization was used to store the bacterium. These genetic changes cause the differences of the genotypes and phenotypes, especially the global regulations, in different K-12 strains.
We sequenced the genome of K-12 strain MC4100 and compared it to other 3 completed K-12 genomes.194 SNPs and many indels events were found between those genomes.
Many phenotype differences can be related to these SNPs and indels. However, the effect of most of these changes kept unknown. Most of these changes occur randomly and spontaneously rather than manual operations. We must consider the genetic differences before our explanation of the experiments using these K-12 strains.
Ⅵ
The theoretical basis of the evolutionary divergence has been discussed in the past century. Traditionally we believed the divergence is due to the complicated adaptation pressure in the environment. However, recent researches proved that the organisms trend to diverged events in a simple constant environment.
The genome sequencing and proteomic researches were applied on 5 phenotypical different derivatives of the E. coli MC4100 that were cultured in Pi-limited chemostat environment for 37 days. We found the E. coli mutated different regulatory genes that related to rpoS to fit the environment. This study indicates the E. coli can increase their fitness to environment by changing different regulatory genes.
引文
[1]Fitch, W. M. Distinguishing homologous from analogous proteins. Syst Zool, 1970,19(2):99-113.
[2]Fitch, W. M. Homology a personal view on some of the problems. Trends Genet,2000,16(5):227-31.
[3]Gerlt, J. A., and P. C. Babbitt. Can sequence determine function? Genome Biol, 2000, 1(5):REVIEWS0005.
[4]Jensen, R. A. Orthologs and paralogs-we need to get it right. Genome Biol, 2001,2(8):INTERACTIONS1002.
[5]Gabaldon, T. Large-scale assignment of orthology:back to phylogenetics? Genome Biol,2008,9(10):235.
[6]Hirsh, A. E., and H. B. Fraser. Protein dispensability and rate of evolution. Nature,2001,411(6841):1046-9.
[7]Koski, L. B., and G. B. Golding. The closest BLAST hit is often not the nearest neighbor. JMol Evol,2001,52(6):540-2.
[8]Tatusov, R.L.,M. Y. Galperin, D. A. Natale,et al.The CPG database:a tool for genome-scale analysis of protein functions and evolution. Nucleic A cids Res,2000,28(1):33-6.
[9]Tatusov, R. L., D. A. Natale, I. V. Garkavtsev, et al. The COG database:new developments in phylogenetic classification of proteins from complete genomes. Nucleic Acids Res,2001,29(1):22-8.
[10]Muller, J., D. Szklarczyk, P. Julien, el al. eggNOG v2.0:extending the evolutionary genealogy of genes with enhanced non-supervised orthologous groups, species and functional annotations. Nucleic Acids Res,2010, 38(Database issue):D190-5.
[11]von Mering, C., M. Huynen, D. Jaeggi, et al. STRING:a database of predicted functional associations between proteins. Nucleic Acids Res,2003, 31(1):258-61.
[12]von Mering, C., L. J. Jensen, B. Snel, et al. STRING:known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res,2005,33(Database issue):D433-7.
[13]O'Brien, K. P., M. Remm, and E. L. Sonnhammer. Inparanoid:a comprehensive database of eukaryotic orthologs. Nucleic Acids Res,2005, 33(Database issue):D476-80.
[14]Li, L., C. J. Stoeckert, Jr., and D. S. Roos. OrthoMCL:identification of ortholog groups for eukaryotic genomes. Genome Res,2003,13(9):2178-89.
[15]Remm, M., C. E. Storm, and E. L. Sonnhammer. Automatic clustering of orthologs and in-paralogs from pairwise species comparisons. JMol Biol, 2001,314(5):1041-52.
[16]Enright, A. J., S. Van Dongen, and C. A. Ouzounis. An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res,2002, 30(7):1575-84.
[17]Morris Goodman, J. C., G. William Moore, A. E. Romero-Herrera and Genji Matsuda. Fitting the Gene Lineage into its Species Lineage, a Parsimony Strategy Illustrated by Cladograms Constructed from Globin Sequences. Systematic Zoology,1979,28(2):132-163.
[18]Zmasek, C. M., and S. R. Eddy. A simple algorithm to infer gene duplication and speciation events on a gene tree. Bioinformatics,2001,17(9):821-8.
[19]Page, R. D., and M. A. Charleston. From gene to organismal phylogeny: reconciled trees and the gene tree/species tree problem. Mol Phylogenet Evol, 1997,7(2):231-40.
[20]Dufayard, J. F., L. Duret, S. Penel, et al. Tree pattern matching in phylogenetic trees:automatic search for orthologs or paralogs in homologous gene sequence databases. Bioinformatics,2005,21(11):2596-603.
[21]Zmasek, C. M., and S. R. Eddy. RIO:analyzing proteomes by automated phylogenomics using resampled inference of orthologs. BMC Bioinformatics, 2002,30:14.
[22]Dehal, P. S., and J. L. Boore. A phylogenomic gene cluster resource:the Phylogenetically Inferred Groups (PhIGs) database. BMC Bioinformatics, 2006,70:201.
[23]Chiu, J. C., E. K. Lee, M. G. Egan, et al. OrthologID:automation of genome-scale ortholog identification within a parsimony framework. Bioinformatics,2006,22(6):699-707.
[24]Rasmussen, M. D., and M. Kellis. Accurate gene-tree reconstruction by learning gene-and species-specific substitution rates across multiple complete genomes. Genome Res,2007,17(12):1932-42.
[25]Hulsen, T., M. A. Huynen, J. de Vlieg, et al. Benchmarking ortholog identification methods using functional genomics data. Genome Biol,2006, 7(4):R31.
[26]Li, H., A. Coghlan, J. Ruan, et al. TreeFam:a curated database of phylogenetic trees of animal gene families. Nucleic Acids Res,2006, 34(Database issue):D572-80.
[27]Chen, F., A. J. Mackey, J. K. Vermunt, et al. Assessing performance of orthology detection strategies applied to eukaryotic genomes. PLoS ONE, 2007,2(4):e383.
[28]Feng, L., P. R. Reeves, R. Lan, et al. A recalibrated molecular clock and independent origins for the cholera pandemic clones. PLoS ONE,2008, 3(12):e4053.
[29]Lefebure, T., and M. J. Stanhope. Evolution of the core and pan-genome of Streptococcus:positive selection, recombination, and genome composition. Genome Biol,2007,8(5):R71.
[30]Makarova, K. S., M. V. Omelchenko, E. K. Gaidamakova, et al. Deinococcus geothermalis:the pool of extreme radiation resistance genes shrinks. PLoS ONE,2007,2(9):e955.
[31]Cui, X., T. Vinar, B. Brejova, et al. Homology search for genes. Bioinformatics,2007,23(13):i97-103.
[32]She, R., J. S. Chu, K. Wang, et al. GenBlastA:enabling BLAST to identify homologous gene sequences. Genome Res,2009,19(1):143-9.
[33]Parkhill, J., B. W. Wren, N. R. Thomson, et al. Genome sequence of Yersinia pestis, the causative agent of plague. Nature,2001,413(6855):523-7.
[34]Parkhill, J., M. Sebaihia, A. Preston, et al. Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica. Nat Genet,2003,35(1):32-40.
[35]Lerat, E., and H. Ochman. Psi-Phi:exploring the outer limits of bacterial pseudogenes. Genome Res,2004,14(11):2273-8.
[36]Kumar, S., K. Tamura, and M. Nei. MEGA:Molecular Evolutionary Genetics Analysis software for microcomputers. Comput Appl Biosci,1994, 10(2):189-91.
[37]Schmidt, H. A., K. Strimmer, M. Vingron, et al. TREE-PUZZLE:maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics,2002,18(3):502-4.
[38]Huson, D. H., and D. Bryant. Application of phylogenetic networks in evolutionary studies. Mol Biol Evol, 2006,23(2):254-67.
[39]Retief, J. D. Phylogenetic analysis using PHYLIP. Methods Mol Biol, 2000, 1320:243-58.
[40]Ochman, H., E. Lerat, and V.Daubin.Examining bacterial species under the specter of gene transfer and exchange. Proc Nail Acad Sci USA,2005, 102(Suppl 1):6595-9.
[41]Touchon, M., C. Hoede, O. Tenaillon, et al. Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths. PLoS Genet, 2009,5(1):e1000344.
[42]Rasko, D. A., M. J. Rosovitz, G. S. Myers, et al. The pangenome structure of Escherichia coli:comparative genomic analysis of E. coli commensal and pathogenic isolates. JBacteriol,2008,190(20):6881-93.
[43]Zhou, Z., X. Li, B. Liu, et al. Derivation of Escherichia coli O157:H7 from its O55:H7 precursor. PLoS ONE,2010,5(1):e8700.
[44]Ogura, Y., T. Ooka, A. Iguchi, et al. Comparative genomics reveal the mechanism of the parallel evolution of 0157 and non-0157 enterohemorrhagic Escherichia coli. Proc Natl Acad Sci U S A,2009, 106(42):17939-44.
[45]Deng, W., J. L. Puente, S. Gruenheid, et al. Dissecting virulence:systematic and functional analyses of a pathogenicity island. Proc Natl Acad Sci U S A, 2004,101(10):3597-602.
[46]Delcher, A. L., D. Harmon, S. Kasif, et al. Improved microbial gene identification with GLIMMER. Nucleic Acids Res,1999,27(23):4636-41.
[47]Yang, F., J. Yang, X. Zhang, et al. Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery. Nucleic Acids Res,2005, 33(19):6445-58.
[48]Iguchi, A., N. R. Thomson, Y. Ogura, et al. Complete genome sequence and comparative genome analysis of enteropathogenic Escherichia coli O127:H6 strain E2348/69. J Bacteriol,2009,191(1):347-54.
[49]Wirth, T., D. Falush, R. Lan, et al. Sex and virulence in Escherichia coli:an evolutionary perspective. Mol Microbiol,2006,60(5):1136-51.
[50]Ohnishi, M., K. Kurokawa, and T. Hayashi. Diversification of Escherichia coli genomes:are bacteriophages the major contributors? Trends Microbiol,2001, 9(10):481-5.
[51]Ohnishi, M., J. Terajima, K. Kurokawa, et al. Genomic diversity of enterohemorrhagic Escherichia coli 0157 revealed by whole genome PCR scanning. Proc Natl Acad Sci USA,2002,99(26):17043-8.
[52]Feil, E. J., M. C. Maiden, M. Achtman, et al. The relative contributions of recombination and mutation to the divergence of clones of Neisseria meningitidis. Mol Biol Evol,1999,16(11):1496-502.
[53]Kimura, M. The neutral theory of molecular evolution. Sci Am,1979, 241(5):98-100
[54]Smith, J. M., N. H. Smith, M. O'Rourke, et al. How clonal are bacteria? Proc Natl Acad Sci USA,1993,90(10):4384-8.
[55]Kuzminov, A. Recombinational repair of DNA damage in Escherichia coli and bacteriophage lambda. Microbiol Mol Biol Rev,1999,63(4):751-813
[56]Courcelle, J., and P. G. Hanawalt. RecA-dependent recovery of arrested DNA replication forks. Annu Rev Genet,2003,37():611-46.
[57]Feil, E. J., E. C. Holmes, D. E. Bessen, et al. Recombination within natural populations of pathogenic bacteria:short-term empirical estimates and long-term phylogenetic consequences. Proc Natl Acad Sci U S A,2001, 98(1):182-7.
[58]Marais, G., D. Mouchiroud, and L. Duret. Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes. Proc Natl Acad Sci USA,2001,98(10):5688-92.
[59]Drysdale, C. M., D. W. McGraw, C. B. Stack, et al. Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA,2000, 97(19):10483-8.
[60]Didelot, X., and D. Falush. Inference of bacterial microevolution using multilocus sequence data. Genetics,2007,175(3):1251-66.
[61]Schierup, M. H., and J. Hein. Consequences of recombination on traditional phylogenetic analysis. Genetics,2000,156(2):879-91.
[62]Schierup, M. H., and J. Hein. Recombination and the molecular clock. Mol Biol Evol,2000,17(10):1578-9.
[63]Weiller, G. F. Phylogenetic profiles:a graphical method for detecting genetic recombinations in homologous sequences. Mol Biol Evol,1998,15(3):326-35.
[64]Hein, J. Reconstructing evolution of sequences subject to recombination using parsimony. Math Biosci,1990,98(2):185-200.
[65]Grassly, N. C., and E. C. Holmes. A likelihood method for the detection of selection and recombination using nucleotide sequences. Mol Biol Evol,1997, 14(3):239-47.
[66]Holmes, E. C., M. Worobey, and A. Rambaut. Phylogenetic evidence for recombination in dengue virus. Mol Biol Evol,1999,16(3):405-9.
[67]Jakobsen, I. B., and S. Easteal. A program for calculating and displaying compatibility matrices as an aid in determining reticulate evolution in molecular sequences. Comput Appl Biosci,1996,12(4):291-5.
[68]Jakobsen, I. B., S. R. Wilson, and S. Easteal. The partition matrix:exploring variable phylogenetic signals along nucleotide sequence alignments. Mol Biol Evol,1997,14(5):474-84.
[69]Sawyer, S. Statistical tests for detecting gene conversion. Mol Biol Evol,1989, 6(5):526-38.
[70]DuBose, R. F., D. E. Dykhuizen, and D. L. Hartl. Genetic exchange among natural isolates of bacteria:recombination within the phoA gene of Escherichia coli. Proc Natl Acad Sci U S A,1988,85(18):7036-40.
[71]Smith, J. M. Analyzing the mosaic structure of genes. J Mol Evol,1992, 34(2):126-9.
[72]Posada, D., and K. A. Crandall. Evaluation of methods for detecting recombination from DNA sequences:computer simulations. Proc Natl Acad Sci USA,2001,98(24):13757-62.
[73]Posada, D. Evaluation of methods for detecting recombination from DNA sequences:empirical data. Mol Biol Evol,2002,19(5):708-17.
[74]Graham, S. W., R. G. Olmstead, and S. C. Barrett. Rooting phylogenetic trees with distant outgroups:a case study from the commelinoid monocots. Mol Biol Evol,2002,19(10):1769-81.
[75]Darling, A. E., T. J. Treangen, X. Messeguer, et al. Analyzing patterns of microbial evolution using the mauve genome alignment system. Methods Mol Biol,2007,396():135-52.
[76]Moran, N. A., H. J. McLaughlin, and R. Sorek. The dynamics and time scale of ongoing genomic erosion in symbiotic bacteria. Science,2009, 323(5912):379-82.
[77]Hanson, R., and T. Hanson. Methanotrophic bacteria. Microbiol Rev,1996, 60(2):439-471.
[78]Dunfield, P., V. Khmelenina, N. Suzina, et al. Methylocella silvestris sp. nov., a novel methanotroph isolated from an acidic forest cambisol. Int J Syst Evol Microbiol,2003,53(Pt 5):1231-1239.
[79]Dedysh, S., N. Panikov, W. Liesack, et al. Isolation of acidophilic methane-oxidizing bacteria from northern peat wetlands. Science,1998, 282(5387):281-284.
[80]Dedysh, S., V. Khmelenina, N. Suzina, et al. Methylocapsa acidiphila gen. nov., sp. nov., a novel methane-oxidizing and dinitrogen-fixing acidophilic bacterium from Sphagnum bog. Int J Syst Evol Microbiol,2002,52(Pt 1):251-261.
[81]Dunfield, P., A. Yuryev, P. Senin, et al. Methane oxidation by an extremely acidophilic bacterium of the phylum Verrucomicrobia. Nature,2007, 450(7171):879-882.
[82]Pol, A., K. Heijmans, H. Harhangi, et al. Methanotrophy below pH 1 by a new Verrucomicrobia species. Nature,2007,450(7171):874-878.
[83]Islam, T., S. Jensen, L. Reigstad, et al. Methane oxidation at 55 degreesC and pH 2 by a thermoacidophilic bacterium belonging to the Verrucomicrobia phylum. Proc Natl Acad Sci USA,2008,105(1):300-304.
[84]Wagner, M., and M. Horn. The Planctomycetes, Verrucomicrobia, Chlamydiae and sister phyla comprise a superphylum with biotechnological and medical relevance. Curr Opin Biotechnol,2006,17(3):241-249.
[85]Strous, M., E. Pelletier, S. Mangenot, et al. Deciphering the evolution and metabolism of an anammox bacterium from a community genome. Nature, 2006,440(7085):790-794.
[86]Hou, S., J. Saw, K. Lee, et al. Genome sequence of the deep-sea gamma-proteobacterium Idiomarina loihiensis reveals amino acid fermentation as a source of carbon and energy. Proc Natl Acad Sci USA,2004, 101(52):18036-18041.
[87]Batzoglou, S., D. Jaffe, K. Stanley, et al. ARACHNE:a whole-genome shotgun assembler. Genome Res,2002,12(1):177-189.
[88]Jaffe, D., J. Butler, S. Gnerre, et al. Whole-genome sequence assembly for mammalian genomes:Arachne 2. Genome Res,2003,13(1):91-96.
[89]Lowe, T. M., and S. R. Eddy. tRNAscan-SE:a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res, 1997,25(5):955-64.
[90]Griffiths-Jones, S., S. Moxon, M. Marshall, et al. Rfam:annotating non-coding RNAs in complete genomes. Nucleic Acids Res,2005, 33(Database issue):D121-D124.
[91]Altschul, S., T. Madden, A. Schaffer, et al. Gapped BLAST and PSJ-BLAST-A new generation of protein database search programs. Nucleic Acids Res, 1997,25(17):3389-3402.
[92]Kanehisa, M., M.Araki, S. Goto, et al. KEGG for linking genomes to life and the environment. Nucleic Acids Res,2008,36(Database issue):D480-D484.
[93]Jobb, G, A. von Haeseler, and K. Strimmer. TREEFINDER:a powerful graphical analysis environment for molecular phylogenetics. BMC Evol Biol, 2004,40:18.
[94]Whelan, S., and N. Goldman. A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol,2001,18(5):691-699.
[95]Rice, P., I. Longden, and A. Bleasby. EMBOSS:the European Molecular Biology Open Software Suite. Trends Genet,2000,16(6):276-277.
[96]Makarova, K., A. Sorokin, P. Novichkov, et al. Clusters of orthologous genes for 41 archaeal genomes and implications for evolutionary genomics of archaea. Biol Direct,2007,2():33.
[97]Thioulouse, J., D. Chessel, S. Doledec, et al. ADE-4:A multivariate analysis and graphical display software. Statistics and Computing,1997,7():75-83.
[98]Kohonen, T. Self-Organizing Maps.2nd ed. German:Springer,1997:22-45.
[99]Grigoriev, A. Analyzing genomes with cumulative skew diagrams. Nucleic Acids Res,1998,26():2286-2290.
[100]Mahillon, J., and M. Chandler. Insertion sequences. Microbiol Mol Biol Rev, 1998,62(3):725-774.
[101]Albrecht, W., A. Fischer, J. Smida, et al. Verrucomicrobium spinosum, an eubacterium representing an ancient line of descent. System Appl Microbiol, 1987,10():57-62.
[102]Ward-Rainey, N., F. Rainey, H. Schlesner, et al. Assignment of hitherto unidentied 16S rDNA species to a main line of descent within the domain Bacteria. Microbiology,1995,141():3247-3250.
[103]Hedlund, B., J. Gosink, and J. Staley. Phylogeny of Prosthecobacter, the fusiform caulobacters:members of a recently discovered division of the bacteria. Int J Syst Bacteriol,1996,46(4):960-966.
[104]Ward, N., F. Rainey, B. Hedlund, et al. Comparative phylogenetic analyses of members of the order Planctomycetales and the division Verrucomicrobia: 23 S rRNA gene sequence analysis supports the 16S rRNA gene sequence-derived phylogeny. Int J Syst Evol Microbiol,2000,50(Pt 6):1965-1972.
[105]Griffiths, E., and R. Gupta. Phylogeny and shared conserved inserts in proteins provide evidence that Verrucomicrobia are the closest known free-living relatives of chlamydiae. Microbiology,2007,153(Pt 8):2648-2654.
[106]Mirkin, B., T. Fenner. M. Galperin, et al. Algorithms for computing parsimonious evolutioriary scenarios for genome evolution, the last universal common ancestor and dominance of horizontal gene transfer in the evolution of prokaryotes. BMC Evol Biol,2003,3():2.
[107]Omelchenko, M., Y. Wolf, E. Gaidamakova, et al. Comparative genomics of Thermus thermophilus and Deinococcus radiodurans:divergent routes of adaptation to thermophily and radiation resistance. BMC Evol Biol,2005, 50:57
[108]Wiener, M. TonB-dependent outer membrane transport:going for Baroque? Curr Opin Struct Biol,2005,15(4):394-400.
[109]Andersen, C. Channel-tunnels:outer membrane components of type I secretion systems and multidrug efflux pumps of Gram-negative bacteria. Rev Physiol Biochem Pharmacol,2003,147():122-165.
[110]Alexander, D., and A. St John. Characterization of the carbon starvation-inducible and stationary phase-inducible gene sip encoding an outer membrane lipoprotein in Escherichia coli. Mol Microbiol,1994, 11(6):1059-1071.
[111]Kane, S., A. Chakicherla, P. Chain, et al. Whole-genome analysis of the methyl tert-butyl ether-degrading beta-proteobacterium Methylibium petroleiphilum PM1.JBacteriol,2007,189(5):1931-1945.
[112]Wilson, S., M. Gleisten, and T. Donohue. Identification of proteins involved in formaldehyde metabolism by Rhodobacter sphaeroides. Microbiology,2008, 154(Pt 1):296-305.
[113]Giovannoni, S., D. Hayakawa, H. Tripp, et al. The small genome of an abundant coastal ocean methylotroph. Environ Microbiol,2008,10(7):1771 1782.
[114]Chistoserdova, L., S. Chen, A. Lapidus, et al. Methylotrophy in Methylobacterium extorquens AM1 from a genomic point of view. J Bacteriol, 2003,185(10):2980-2987.
[115]Jordan, D., and W. Ogren. Species variation in kinetic properties of ribulose 1,5-bisphosphate carboxylase/oxygenase. Arch Biochem Biophys,1983, 227(2):425-433.
[116]Chistoserdov, A., L. Chistoserdova, W. McIntire, et al. Genetic organization of the mau gene cluster in Methylobacterium extorquens AM1:complete nucleotide sequence and generation and characteristics of mau mutants.J Bacteriol,1994,176(13):4052-4065.
[117]Davidson, V. Methylamine dehydrogenase. Structure and function of electron transfer complexes. Subcell Biochem,2000,35():119-143.
[118]Anthony, C. The Biochemistry of Methylotrophs. USA:Academic Pr, 1982:110-7.
[119]Kelly, D., C. Anthony, and J. Murrell. Insights into the obligate methanotroph Methylococcus capsulatus. Trends Microbiol,2005,13(5):195-198.
[120]Chistoserdova, L., A. Lapidus, C. Han, et al. Genome of Methylobacillus flagellatus, molecular basis for obligate methylotrophy, and polyphyletic origin of methylotrophy. J Bacteriol,2007,189(11):4020-4027.
[121]Ward, N., O. Larsen, J. Sakwa, et al Genomic insights into methanotrophy: the complete genome sequence of Methylococcus capsulatus (Bath). PLoS Biol,2004,2(10):e303.
[122]El Yacoubi, B., S. Bonnett. J. Anderson, et al. Discovery of a new prokaryotic type I GTP cyclohydrolase family. J Biol Chem,2006,281(49):37586-37593.
[123]Levin, I., M. Mevarech, and B. Palfey. Characterization of a novel bifunctional dihydropteroate synthase/dihydropteroate reductase enzyme from Helicobacter pylori. J Bacteriol,2007,189(11):4062-4069.
[124]Meister, A., and P. Fraser. Enzymatic formation of L-asparagine by transamination. J Biol Chem,1954,210(1):37-43.
[125]Oakley, C., and J. Murrell. Cloning of nitrogenase structural genes from the obligate methanotroph Methylococcus capsulatus (Bath). FEMS Microbiol Lett,1991,62(2-3):121-125.
[126]Pilhofer, M., G. Rosati, W. Ludwig, et al. Coexistence of tubulins and ftsZ in different Prosthecobacter species. Mol Biol Evol,2007,24(7):1439-1442.
[127]Jenkins, C., R. Samudrala, I. Anderson, et al. Genes for the cytoskeletal protein tubulin in the bacterial genus Prosthecobacter. Proc Natl Acad Sci USA,2002,99(26):17049-17054.
[128]Staley, J., H. Bouzek, and C. Jenkins. Eukaryotic signature proteins of Prosthecobacter dejongeii and Gemmata sp. Wa-1 as revealed by in silico analysis. FEMS Microbiol Lett,2005,243(1):9-14.
[129]Costerton, J., L. Poffenroth, J. Wilt, et al. Ultrastructural studies of the nucleoids of the pleomorphic forms of Chlamydia psittaci 6BC:a comparison with bacteria. Can J Microbiol,1976,22(1):16-28.
[130]Lindsay, M., R. Webb, M. Strous, et al. Cell compartmentalisation in planctomycetes:novel types of structural organisation for the bacterial cell. Arch Microbiol,2001,175(6):413-429.
[131]Fuerst, J. Intracellular compartmentation in planctomycetes. Annu Rev Microbiol 2005,59():299-328.
[132]Fuchsman, C., and G. Rocap. Whole-genome reciprocal BLAST analysis reveals that planctomycetes do not share an unusually large number of genes with Eukarya and Archaea. Appl Environ Microbiol,2006,72(10):6841-6844.
[133]Pilhofer, M., K. Rappl, C. Eckl, et al. Characterization and evolution of cell division and cell wall synthesis genes in the bacterial phyla Verrucomicrobia, Lentisphaerae, Chlamydiae, and Planctomycetes and phylogenetic comparison with rRNA genes. J Bacteriol,2008,190(9):3192-3202.
[134]Foster, J. Escherichia coli acid resistance:tales of an amateur acidophile. Nat Rev Microbiol,2004,2(11):898-907.
[135]Griswold, A., Y. Chen, and R. Burne. Analysis of an agmatine deiminase gene cluster in Streptococcus mutans UA159. J Bacteriol,2004,186(6):1902-1904.
[136]Stingl, K., K. Altendorf, and E. Bakker. Acid survival of Helicobacter pylori: how does urease activity trigger cytoplasmic pH homeostasis? Trends Microbiol,2002,10(2):70-74.
[137]Strausak,D.,M.Waser,and M.Solioz.Functional expression of the Enterococcus hirae NaH-antiporter in Escherichia coli. J Biol Chem,1993, 268(35):26334-26337.
[138]Makarova, K., N. Grishin, S. Shabalina et al. A putative RNA-interference-based immune system in prokaryotes:computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol Direct,2006, 1():7.
[139]Barrangou, R., C. Fremaux, H. Deveau, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science,2007,315(5819):1709-1712.
[140]Makarova, K., Y. Wolf, and E. Koonin. Potential genomic determinants of hyperthermophily. Trends Genet,2003,19(4):172-176.
[141]Gerdes, K., S. Christensen, and A. Lobner-Olesen. Prokaryotic toxin-antitoxin stress response loci. Nature reviews,2005,3(5):371-382.
[142]Matic, I., F. Taddei, and M. Radman. Genetic barriers among bacteria. Trends Microbiol,1996,4(2):69-72.
[143]Gordon, D. M., and F. FitzGibbon. The distribution of enteric bacteria from Australian mammals:host and geographical effects. Microbiology,1999,145 (Pt 10)2663-71.
[144]Souza, V., M. Rocha, A. Valera, et al. Genetic structure of natural populations of Escherichia coli in wild hosts on different continents. Appl Environ Microbiol,1999,65(8):3373-85.
[145]Kaper, J. B., J. P. Nataro, and H. L. Mobley. Pathogenic Escherichia coli. Nat Rev Microbiol,2004,2(2):123-40.
[146]Riley, L. W., R. S. Remis, S. D. Helgerson, et al. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med,1983, 308(12):681-5.
[147]Banatvala, N., P. M. Griffin, K. D. Greene, et al. The United States National Prospective Hemolytic Uremic Syndrome Study:microbiologic, serologic, clinical, and epidemiologic findings. J Infect Dis,2001,183(7):1063-70.
[148]Whittam, T. S., M. L. Wolfe, I. K. Wachsmuth, et al. Clonal relationships among Escherichia coli strains that cause hemorrhagic colitis and infantile diarrhea. Infect Immun,1993,61(5):1619-29.
[149]Feng, P., K. A. Lampel, H. Karch, et al. Genotypic and phenotypic changes in the emergence of Escherichia coli O157:H7. J Infect Dis,1998, 177(6):1750-3.
[150]Kozub-Witkowski, E., G. Krause, G. Frankel, et al. Serotypes and virutypes of enteropathogenic and enterohaemorrhagic Escherichia coli strains from stool samples of children with diarrhoea in Germany. J Appl Microbiol,2008, 104(2):403-10.
[151]Leopold, S. R., V. Magrini, N. J. Holt, et al. A precise reconstruction of the emergence and constrained radiations of Escherichia coli 0157 portrayed by backbone concatenomic analysis. Proc Natl Acad Sci U S A,2009, 106(21):8713-8.
[152]Gordon, D., C. Abajian, and P. Green. Consed:a graphical tool for sequence finishing. Genome Res,1998,8(3):195-202.
[153]Delcher, A. L., K. A. Bratke, E. C. Powers, et al. Identifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics,2007,23(6):673-9.
[154]Carver, T., M. Berriman, A. Tivey, et al. Artemis and ACT:viewing, annotating and comparing sequences stored in a relational database. Bioinformatics,2008,24(23):2672-6.
[155]Emmert, D. B., P. J. Stoehr, G. Stoesser, et al. The European Bioinformatics Institute (EBI) databases. Nucleic Acids Res,1994,22(17):3445-9.
[156]Benson, D. A., I. Karsch-Mizrachi, D. J. Lipman, et al. GenBank. Nucleic Acids Res,2000,28(1):15-8.
[157]Bairoch, A., and R. Apweiler. The SWISS-PROT protein sequence data bank and its new supplement TREMBL. Nucleic Acids Res,1996,24(1):21-5.
[158]Drake, J. W. Too many mutants with multiple mutations. Crit Rev Biochem Mol Biol,2007,42(4):247-58.
[159]Ferenci, T., Z. Zhou, T. Betteridge, et al. Genomic Sequencing Reveals Regulatory Mutations and Recombinational Events in the Widely Used MC4100 Lineage of Escherichia coli K-12. JBacteriol,2009, 191(12):4025-9.
[160]Schmidt, H. A.,Strimmer K., Vingron M., et al. TREE-PUZZLE:maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics.,2002,18(3):502-4.
[161]Gascuel, O. BIONJ:an improved version of the NJ algorithm based on a simple model of sequence data. Mol Biol Evol,1997,14(7):685-95.
[162]Guttman, D. S., and D. E. Dykhuizen. Clonal divergence in Escherichia coli as a result of recombination, not mutation. Science,1994,266(5189):1380-3.
[163]Whittam, T. S. Genetic variation and evolutionary processes in natural populations of Escherichia coli. Washington:ASM Press,1996:2708-2720.
[164]Zhang, W., W. Qi, T. J. Albert, et al. Probing genomic diversity and evolution of Escherichia coli 0157 by single nucleotide polymorphisms. Genome Res, 2006,16(6):757-67.
[165]Wick, L. M., W. Qi, D. W. Lacher, et al. Evolution of genomic content in the stepwise emergence of Escherichia coli O157:H7. J Bacteriol,2005, 187(5):1783-91.
[166]Tarr, P. I., L. M. Schoening, Y. L. Yea, et al. Acquisition of the rfb-gnd cluster in evolution of Escherichia coli 055 and 0157. J Bacteriol,2000, 182(21):6183-91.
[167]Wang, L., S. Huskic, A. Cisterne, et al. The O-antigen gene cluster of Escherichia coli 055:H7 and identification of a new UDP-GlcNAc C4 epimerase gene. JBacteriol,2002,184(10):2620-5.
[168]Milkman, R., E. Jaeger, and R. D. McBride. Molecular evolution of the Escherichia coli chromosome. Ⅵ. Two regions of high effective recombination. Genetics,2003,163(2):475-83.
[169]Link, C. D., and A. M. Reiner. Genotypic exclusion:a novel relationship between the ribitol-arabitol and galactitol genes of E. coli. Mol Gen Genet, 1983,189(2):337-9.
[170]Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev,2003,67(4):593-656.
[171]Hill, C. W. Large genomic sequence repetitions in bacteria:lessons from rRNA operons and Rhs elements. Res Microbiol,1999,150(9-10):665-74.
[172]Hayashi, T., K. Makino, M. Ohnishi, et al. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res,2001,8(1):11-22.
[173]Perna, N. T., G Plunkett,3rd, V. Burland, et al. Genome sequence of eriterohaemorrhagic Escherichia coli O151:H7. Nature,2001, 409(6819):529-33.
[174]Benz, I., and M. A. Schmidt. Cloning and expression of an adhesin (AIDA-I) involved in diffuse adherence of enteropathogenic Escherichia coli. Infect Immun,1989,57(5):1506-11.
[175]Henderson, I. R., F. Navarro-Garcia, M. Desvaux, et al. Type V protein secretion pathway:the autotransporter story. Microbiol Mol Biol Rev,2004, 68(4):692-744.
[176]Ho, T. D., B. M. Davis, J. M. Ritchie, et al. Type 2 secretion promotes enterohemorrhagic Escherichia coli adherence and intestinal colonization. Infect Immun,2008,76(5):1858-65.
[177]Morabito, S., R. Tozzoli, E. Oswald, et al. A mosaic pathogenicity island made up of the locus of enterocyte effacement and a pathogenicity island of Escherichia coli O157:H7 is frequently present in attaching and effacing E. coli. Infect Immun,2003,71(6):3343-8.
[178]Karmali, M. A., M. Mascarenhas, S. Shen, et al. Association of genomic O island 122 of Escherichia coli EDL 933 with verocytotoxin-producing Escherichia coli seropathotypes that are linked to epidemic and/or serious disease. J Clin Microbiol,2003,41(11):4930-40.
[179]Stevens, M. P., A. J. Roe, I. Vlisidou, et al. Mutation of toxB and a truncated version of the efa-1 gene in Escherichia coli O157:H7 influences the expression and secretion of locus of enterocyte effacement-encoded proteins but not intestinal colonization in calves or sheep. Infect Immun,2004, 72(9):5402-11.
[180]Beinke, C., S. Laarmann, C. Wachter, et al. Diffusely adhering Escherichia coli strains induce attaching and effacing phenotypes and secrete homologs of Esp proteins. Infect Immun,1998,66(2):528-39.
[181]Trabulsi, L. R., R. Keller, and T. A. Tardelli Gomes. Typical and atypical enteropathogenic Escherichia coli. Emerg Infect Dis,2002,8(5):508-13.
[182]Brunder, W., H. Karch, and H. Schmidt. Complete sequence of the large virulence plasmid pSFO157 of the sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H-strain 3072/96. Int J Med Microbiol,2006, 296(7):467-74.
[183]Anthony, K. G., W. A. Klimke, J. Manchak, et al. Comparison of proteins involved in pilus synthesis and mating pair stabilization from the related plasmids F and R100-1:insights into the mechanism of conjugation. J Bacteriol,1999,181(17):5149-59.
[184]Lawley, T. D., W. A. Klimke, M. J. Gubbins, et al. F factor conjugation is a true type Ⅳ secretion system. FEMS Microbiol Lett,2003,224(1):1-15.
[185]Gruenheid, S., I. Sekirov, N. A. Thomas, et al. Identification and characterization of NleA, a non-LEE-encoded type III translocated virulence factor of enterohaemorrhagic Escherichia coli O157:H7. Mol Microbiol,2004, 51(5):1233-49.
[186]Creuzburg, K., and H. Schmidt. Molecular characterization and distribution of genes encoding members of the type III effector nleA family among pathogenic Escherichia coli strains. J Clin Microbiol,2007,45(8):2498-507.
[187]Nataro, J. P., and J. B. Kaper. Diarrheagenic Escherichia coli. Clin Microbiol Rev,1998,11(1):142-201.
[188]Tobe, T., S. A. Beatson, H. Taniguchi, et al. An extensive repertoire of type III secretion effectors in Escherichia coli 0157 and the role of lambdoid phages in their dissemination. Proc Natl Acad Sci USA,2006,103(40):14941-6.
[189]Drago-Serrano, M. E., S. G. Parra, and H. A. Manjarrez-Hernandez. EspC, an autotransporter protein secreted by enteropathogenic Escherichia coli (EPEC), displays protease activity on human hemoglobin. FEMS Microbiol Lett,2006, 265(1):35-40.
[190]Stein, M., B. Kenny, M. A. Stein, et al. Characterization of EspC, a 110-kilodalton protein secreted by enteropathogenic Escherichia coli which is homologous to members of the immunoglobulin A protease-like family of secreted proteins. J Bacteriol,1996,178(22):6546-54.
[191]An, H., J. M. Fairbrother, C. Desautels, et al. Distribution of a novel locus called Paa (porcine attaching and effacing associated) among enteric Escherichia coli. Adv Exp Med Biol,1999,4730:179-84.
[192]Afset, J. E., G. Bruant, R. Brousseau, et al. Identification of virulence genes linked with diarrhea due to atypical enteropathogenic Escherichia coli by DNA microarray analysis and PCR. J Clin Microbiol,2006,44(10):3703-11.
[193]Frankel, G., and A. D. Phillips. Attaching effacing Escherichia coli and paradigms of Tir-triggered actin polymerization:getting off the pedestal. Cell Microbiol,2008,10(3):549-56.
[194]Lee, C. A., and S. Falkow. The ability of Salmonella to enter mammalian cells is affected by bacterial growth state. Proc Natl Acad Sci USA,1990, 87(11):4304-8.
[195]Rosenshine, I., S. Ruschkowski, and B. B. Finlay. Expression of attaching/effacing activity by enteropathogenic Escherichia coli depends on growth phase, temperature, and protein synthesis upon contact with epithelial cells. Infect Immun,1996,64(3):966-73.
[196]Sperandio, V., J. L. Mellies, W. Nguyen, et al. Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli. Proc Natl Acad Sci USA,1999,96(26):15196-201.
[197]Abe, H., I. Tatsuno, T. Tobe. et al. Bicarbonate ion stimulates the expression of locus of enterocyte effacement-encoded genes in enterohemorrhagic 'Escherichia coli O157:H7.Infect Immun,2002,70(7):3500-9.
[198]Bachmann, B. J. Derivations and genotypes of some mutant derivatives of Escherichia coli. Washington DC:American Society for Microbiology, 1996:2460-2488.
[199]Blattner, F. R., G. Plunkett,3rd, C. A. Bloch, et al. The complete genome sequence of Escherichia coli K-12. Science,1997,277(5331):1453-62.
[200]Hayashi, K., N. Morooka, Y. Yamamoto, et al. Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol,2006,2():2006 0007.
[201]Durfee, T., R. Nelson, S. Baldwin, et al. The complete genome sequence of Escherichia coli DH10B:insights into the biology of a laboratory workhorse. J Bacteriol,2008,190(7):2597-606.
[202]Englesberg, E., R. L. Anderson, R. Weinberg, et al. L-Arabinose-sensitive, L-ribulose 5-phosphate 4-epimerase-deficient mutants of Escherichia coli. J Bacteriol,1962,84():137-46.
[203]Liu, G. R., K. Edwards, A. Eisenstark, et al. Genomic diversification among archival strains of Salmonella enterica serovar typhimurium LT7. J Bacteriol, 2003,185(7):2131-42.
[204]Naas, T., M. Blot, W. M. Fitch, et al. Insertion sequence-related genetic variation in resting Escherichia coli K-12. Genetics,1994,136(3):721-30.
[205]Casadaban, M. J. Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage lambda and Mu. J Mol Biol, 1976,104(3):541-55.
[206]Silhavy, T. J., and J. R. Beckwith. Uses of lac fusions for the study of biological problems. Microbiol Rev,1985,49(4):398-418.
[207]Silhavy, T. J., M. J. Casadaban, H. A. Shuman, et al. Conversion of beta-galactosidase to a membrane-bound state by gene fusion. Proc Natl Acad Sci USA,1976,73(10):3423-7.
[208]Wientjes, F. B., and N. Nanninga. Rate and topography of peptidoglycan synthesis during cell division in Escherichia coli:concept of a leading edge. J Bacteriol,1989,171(6):3412-9.
[209]Khodursky, A. B., B. J. Peter, M. B. Schmid, et al. Analysis of topoisomerase function in bacterial replication fork movement:use of DNA microarrays. Proc Natl Acad Sci USA,2000,97(17):9419-24.
[210]Prasad Maharjan, R., P. L. Yu, S. Seeto, et al. The role of isocitrate lyase and the glyoxylate cycle in Escherichia coli growing under glucose limitation. Res Microbiol,2005,156(2):178-83.
[211]Lange, R., and R. Hengge-Aronis. Identification of a central regulator of stationary-phase gene expression in Escherichia coli. Mol Microbiol,1991, 5(1):49-59.
[212]Ishihama, Y, T. Schmidt, J. Rappsilber, et al. Protein abundance profiling of the Escherichia coli cytosol. BMC Genomics,2008,9():102.
[213]Maharjan, R., S. Seeto, L. Notley-McRobb, et al. Clonal adaptive radiation in a constant environment. Science,2006,313(5786):514-7.
[214]Heath, J. D., J. D. Perkins, B. Sharma, et al. NotI genomic cleavage map of Escherichia coli K-12 strain MG1655. J Bacteriol,1992,174(2):558-67.
[215]Peters, J. E., T. E. Thate, and N. L. Craig. Definition of the Escherichia coli MC4100 genome by use of a DNA array. J Bacteriol, 2003,185(6):2017-21.
[216]Sawers, R. G. Expression of fnr is constrained by an upstream IS5 insertion in certain Escherichia coli K-12 strains. J Bacteriol, 2005,187(8):2609-17.
[217]King, T., A. Ishihama, A. Kori, et al. A regulatory trade-off as a source of strain variation in the species Escherichia coli. J Bacteriol,2004, 186(17):5614-20.
[218]Spira, B., X. Hu, and T. Ferenci. Strain variation in ppGpp concentration and RpoS levels in laboratory strains of Escherichia coli K-12. Microbiology, 2008,154(Pt 9):2887-95.
[219]Margulies, M., M. Egholm, W. E. Altman, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature,2005, 437(7057):376-80.
[220]Schuster, S. C. Next-generation sequencing transforms today's biology. Nat Methods,2008,5(1):16-8.
[221]Bentley, D. R., S. Balasubramanian, H. P. Swerdlow, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature, 2008,456(7218):53-9.
[222]McKernan, K. J., H. E. Peckham, G. L. Costa, et al. Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res,2009, 19(9):1527-41.
[223]Wheeler, D. A., M. Srinivasan, M. Egholm, et al. The complete genome of an individual by massively parallel DNA sequencing. Nature,2008, 452(7189):872-6.
[224]Wang, J., W. Wang, R. Li, et al. The diploid genome sequence of an Asian individual. Nature,2008,456(7218):60-5.
[225]Zerbino, D. R., and E. Birney. Velvet:algorithms for de novo short read assembly using de Bruijn graphs. Genome Res,2008,18(5):821-9.
[226]Chaisson, M. J., D. Brinza, and P. A. Pevzner. De novo fragment assembly with short mate-paired reads:Does the read length matter? Genome Res,2009, 19(2):336-46.
[227]Li, R., Y. Li, K. Kristiansen, et al. SOAP:short oligonucleotide alignment program. Bioinformatics,2008,24(5):713-4.
[228]Boeckmann, B., A. Bairoch, R. Apweiler, et al. The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res,2003, 31(1):365-70.
[229]Goldberg, S. M., J. Johnson, D. Busam, et al. A Sanger/pyrosequencing hybrid approach for the generation of high-quality draft assemblies of marine microbial genomes. Proc Natl Acad Sci USA,2006,103(30):11240-5.
[230]Notley, L., and T. Ferenci. Differential expression of mal genes under cAMP and endogenous inducer control in nutrient-stressed Escherichia coli. Mol Microbiol,1995,16(1):121-9.
[231]Hall, B. G, and P. M. Sharp. Molecular population genetics of Escherichia coli:DNA sequence diversity at the celC,err,and gutB loci of natural isolates. Mol Biol Evol,1992,9(4):654-65.
[232]Saier, M. H., Jr., and T. M. Ramseier. The catabolite repressor/activator (Cra) protein of enteric bacteria. J Bacteriol,1996,178(12):3411-7.
[233]Becker, G., E. Klauck, and R. Hengge-Aronis. The response regulator RssB, a recognition factor for sigmaS proteolysis in Escherichia coli, can act like an anti-sigmaS factor. Mol Microbiol,2000,35(3):657-66
[234]Zhou, Y., S. Gottesman, J. R. Hoskins, et al. The RssB response regulator directly targets sigma(S) for degradation by ClpXP. Genes Dev,2001, 15(5):627-37.
[235]Bremer, E., T. J. Silhavy, and G. M. Weinstock. Transposable lambda placMu bacteriophages for creating lacZ operon fusions and kanamycin resistance insertions in Escherichia coli. J Bacteriol,1985,162(3):1092-9.
[236]Lindsey, D. F., D. A. Mullin, and J. R. Walker. Characterization of the cryptic lambdoid prophage DLP12 of Escherichia coli and overlap of the DLP12 integrase gene with the tRNA gene argU. JBacteriol,1989, 171(11):6197-205.
[237]Herring, C. D., A. Raghunathan, C. Honisch, et al. Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale. Nat Genet,2006,38(12):1406-12.
[238]Barrick, J. E., D. S. Yu, S. H. Yoon, et al. Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature,2009, 461(7268):1243-7.
[239]Kassen, R., and P. B. Rainey. The ecology and genetics of microbial diversity. Annu Rev Microbiol,2004,58():207-31.
[240]Rozen, D. E., N. Philippe, J. Arjan de Visser, et al. Death and cannibalism in a seasonal environment facilitate bacterial coexistence. Ecol Lett,2009, 12(1):34-44.
[241]Rainey, P. B., and M. Travisano. Adaptive radiation in a heterogeneous environment. Nature,1998,394(6688):69-72.
[242]Barrett, R. D., and G. Bell. The dynamics of diversification in evolving Pseudomonas populations. Evolution,2006,60(3):484-90.
[243]Zhong, S., A. Khodursky, D. E. Dykhuizen, et al. Evolutionary genomics of ecological specialization. Proc Natl Acad Sci U S A,2004,101(32):11719-24.
[244]Treves, D. S., S. Manning, and J. Adams. Repeated evolution of an acetate-crossfeeding polymorphism in long-term populations of Escherichia coli. Mol Biol Evol,1998,15(7):789-97.
[245]Schluter, D. Evidence for ecological speciation and its alternative. Science, 2009,323(5915):737-41.
[246]Gudelj, I., R. E. Beardmore, S. S. Arkin, et al. Constraints on microbial metabolism drive evolutionary diversification in homogeneous environments. J Evol Biol,2007,20(5):1882-9.
[247]Maharjan, R. P., S. Seeto, and T. Ferenci. Divergence and redundancy of transport and metabolic rate-yield strategies in a single Escherichia coli population. J Bacteriol,2007,189(6):2350-8.
[248]Edelman, G. M., and J. A. Gally. Degeneracy and complexity in biological systems. Proc Natl Acad Sci USA,2001,98(24):13763-8.
[249]Carroll, S. B. Evo-devo and an expanding evolutionary synthesis:a genetic theory of morphological evolution. Cell,2008,134(1):25-36.
[250]Chang, Y.W., F. G. Robert Liu. N. Yu, et al. Roles of cis-and trans-changes in the regulatory evolution of genes in the gluconeogenic pathway in yeast. Mol Biol Evol,2008,25(9):1863-75.
[251]Hunter, P. The great leap forward. Major evolutionary jumps might be caused by changes in gene regulation rather than the emergence of new genes. EMBO Rep,2008,9(7):608-11.
[252]Wittkopp, P. J., B. K. Haerum, and A. G. Clark. Evolutionary changes in cis and trans gene regulation. Nature,2004,430(6995):85-8.
[253]Barrier, M., R. H. Robichaux, and M. D. Purugganan. Accelerated regulatory gene evolution in an adaptive radiation. Proc Natl Acad Sci USA,2001, 98(18):10208-13.
[254]Philippe, N., E. Crozat, R. E. Lenski, et al. Evolution of global regulatory networks during a long-term experiment with Escherichia coli. Bioessays, 2007,29(9):846-60.
[255]Cooper, T. F., S. K. Remold, R. E. Lenski, et al. Expression profiles reveal parallel evolution of epistatic interactions involving the CRP regulon in Escherichia coli. PLoS Genet,2008,4(2):e35.
[256]Kinnersley, M. A., W. E. Holben, and F. Rosenzweig. E Unibus Plurum: genomic analysis of an experimentally evolved polymorphism in Escherichia coli. PLoS Genet,2009,5(11):e1000713.
[257]Torriani, A. From cell membrane to nucleotides:the phosphate regulon in Escherichia coli. Bioessays,1990,12(8):371-6.
[258]Ferenci, T. Regulation by nutrient limitation. Curr Opin Microbiol,1999, 2(2):208-13.
[259]Bougdour, A., S. Wickner, and S. Gottesman. Modulating RssB activity:IraP, a novel regulator of sigma(S) stability in Escherichia coli. Genes Dev,2006, 20(7):884-97.
[260]Weber, H., T. Polen, J. Heuveling, et al. Genome-wide analysis of the general stress response network in Escherichia coli:sigmaS-dependent genes, promoters, and sigma factor selectivity. J Bacteriol,2005,187(5):1591-603.
[261]Spira, B., N. Silberstein, and E. Yagil. Guanosine 3',5'-bispyrophosphate (ppGpp) synthesis in cells of Escherichia coli starved for Pi. J Bacteriol,1995, 177(14):4053-8.
[262]Durfee, T., A. M. Hansen, H. Zhi, et al. Transcription profiling of the stringent response in Escherichia coli. J Bacteriol,2008,190(3):1084-96.
[263]Ferenci, T. Bacterial physiology, regulation and mutational adaptation in a chemostat environment. Adv Microb Physiol,2008,53():169-229.
[264]Li, H., and R. Durbin. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics,2010,26(5):589-95.
[265]Taschner, N. P., E. Yagil, and B. Spira. A differential effect of sigmaS on the expression of the PHO regulon genes of Escherichia coli. Microbiology,2004, 150(Pt 9):2985-92.
[266]Gottesman, S. The small RNA regulators of Escherichia coli:roles and mechanisms*. Annu Rev Microbiol,2004,58():303-28.
[267]Tsui, H. C., H. C. Leung, and M. E. Winkler. Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12. Mol Microbiol,1994,13(1):35-49.
[268]Hengge-Aronis, R. Signal transduction and regulatory mechanisms involved in control of the sigma(S) (RpoS) subunit of RNA polymerase. Microbiol Mol Biol Rev,2002,66(3):373-95
[269]Valentin-Hansen, P., J. Johansen, and A. A. Rasmussen. Small RNAs controlling outer membrane porins. Curr Opin Microbiol,2007,10(2):152-5.
[270]Repoila, F., N. Majdalani, and S. Gottesman. Small non-coding RNAs, co-ordinators of adaptation processes in Escherichia coli:the RpoS paradigm. Mol Microbiol,2003,48(4):855-61.
[271]Ferenci, T. Maintaining a healthy SPANC balance through regulatory and mutational adaptation. Mol Microbiol,2005,57(1):1-8.
[272]Gentry, D. R., and M. Cashel. Mutational analysis of the Escherichia coli spoT gene identifies distinct but overlapping regions involved in ppGpp synthesis and degradation. Mol Microbiol,1996,19(6):1373-84.
[273]Hoffmann, A. A., R. Hallas, C. Sinclair, et al. Levels of variation in stress resistance in drosophila among strains, local populations, and geographic regions:patterns for desiccation, starvation, cold resistance, and associated traits. Evolution,2001,55(8):1621-30.
[274]De Paepe, M., and F. Taddei. Viruses' life history:towards a mechanistic basis of a trade-off between survival and reproduction among phages. PLoS Biol, 2006,4(7):e193.
[275]Lenski, R. E., J. E. Barrick, and C. Ofria. Balancing robustness and evolvability. PLoS Biol,2006,4(12):e428.
[276]Rosenzweig, R. F., R. R. Sharp, D. S. Treves, et al. Microbial evolution in a simple unstructured environment:genetic differentiation in Escherichia coli. Genetics,1994,137(4):903-17.
[277]Fitzpatrick, B. M., J. A. Fordyce, and S. Gavrilets. What, if anything, is sympatric speciation? JEvol Biol,2008,21(6):1452-9.