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The evolutionary characterisation of bacterial diversity from DNA sequence data

DNA 序列数据的细菌多样性的进化表征

基本信息

批准号：
BB/G004250/1
负责人：
Timothy Barraclough
金额：
$ 40.39万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG004250%2F1
关键词：
evolutionary characterisation bacterial diversity DNA

项目摘要

DNA sequence data are being increasingly used to characterise biodiversity, not least in groups of organisms in which traditional taxonomic approaches have proved of limited use. One group that is particularly dependent on DNA approaches, and particularly challenging, is the bacteria. Only a tiny fraction of bacteria are culturable and the true species richness of bacteria, as defined by current methodology, could number in the billions. However, although a wealth of sequence data for bacteria is becoming available, there remain major theoretical challenges to characterising the diversity of bacteria. First and foremost, bacteria have proved difficult to accommodate within traditional species definitions developed for plants and animals, because of important differences in their mode of inheritance. Bacteria are clonal (they reproduce by simple division of cells), yet they can exchange DNA by a variety of mechanisms, some of which occur most often between closer relatives whereas others occur between distantly related strains. However, the same basic processes cause diversification in bacteria as in plants and animals: the question is to what extent do these processes act together to produce units equivalent to species, rather than acting separately on different genes to produce a more complex pattern of diversity. On top of this problem, methods for identifying evolutionarily and biologically meaningful units of diversity from DNA data are in their infancy: most studies use crude thresholds of DNA divergence to delimit species, or graphical approaches to delimit species by eye, rather than statistical models to test for the action of different processes known to be important for causing diversity to evolve. This project will develop new methods for characterising the diversity of bacteria and use them to test whether bacteria do fall into simple units of diversity equivalent to species, or whether a more complex model of diversity is needed. First, we will develop a broadly applicable suite of new methods for identifying units of diversity from DNA sequence data. The methods will range from those suitable when only a single gene region has been sequenced from each individual, to those suitable when several genes have been sequenced from each individual, called multi-locus sequence analysis (MLSA). Software will be made freely available to enable other researchers to apply our methods in a broad range of applications. The software will be tested in relation to two existing databases, one compiling sequences of a single gene region (16S rRNA) from several hundred thousand isolates of bacteria, and one sampling bacterial genomes from environmental samples. To answer our central question concerning the simplicity or complexity of bacterial diversity, we will generate a new dataset compiling gene sequence data for the Bacillus cereus species complex. This group includes strains with beneficial roles in soil and the plant surfaces, such as nutrient cycling and blocking of plant pathogens, whereas genetically similar strains are disease agents in humans, other mammals or insects. Going beyond previous studies, we will sequence genes with important ecological functions, such as those involved in attacking host defences, as well as the so-called 'house-keeping' genes involved in basic biological processes that are normally used in MLSA studies. This will allow a more comprehensive test of different scenarios for diversification, in particular comparing functional units with different ecological attributes. The results will indicate whether simple units of diversity exist or whether the pattern of diversification is different depending on which set of genes or which aspect of diversity is being considered. The outputs will establish new methods and evidence both for practical delimitation of bacterial diversity and for theoretical debates on the evolution of diversity and the nature of species.

DNA序列数据正越来越多地用于生物多样性的分类，尤其是在传统分类方法已被证明用途有限的生物群体中。一个特别依赖DNA方法的群体，特别具有挑战性的是细菌。只有一小部分细菌是可培养的，而按照目前的方法学定义，细菌的真正物种丰富度可能达到数十亿。然而，尽管细菌的大量序列数据变得可用，但在表征细菌多样性方面仍然存在重大的理论挑战。首先，细菌已被证明难以适应为植物和动物开发的传统物种定义，因为它们的遗传模式存在重大差异。细菌是克隆的（它们通过简单的细胞分裂繁殖），但它们可以通过各种机制交换DNA，其中一些最常发生在近亲之间，而另一些则发生在远亲菌株之间。然而，与植物和动物相同的基本过程导致细菌的多样性：问题是这些过程在多大程度上共同作用以产生相当于物种的单位，而不是单独作用于不同的基因以产生更复杂的多样性模式。除了这个问题之外，从DNA数据中识别具有进化和生物学意义的多样性单位的方法还处于起步阶段：大多数研究使用DNA分歧的粗略阈值来划分物种，或者使用图形方法来通过眼睛划分物种，而不是使用统计模型来测试已知对导致多样性进化很重要的不同过程的作用。该项目将开发表征细菌多样性的新方法，并使用它们来测试细菌是否属于相当于物种的简单多样性单位，或者是否需要更复杂的多样性模型。首先，我们将开发一套广泛适用的新方法，用于从DNA序列数据中识别多样性单位。这些方法的范围将从那些适合于从每个个体中仅测序单个基因区域的方法，到那些适合于从每个个体中测序几个基因的方法，称为多位点序列分析（MLSA）。软件将免费提供，使其他研究人员能够在广泛的应用中应用我们的方法。该软件将在两个现有的数据库中进行测试，一个数据库汇编了数十万细菌分离物的单个基因区域（16S rRNA）的序列，另一个数据库从环境样本中采集细菌基因组。为了回答我们关于细菌多样性的简单性或复杂性的中心问题，我们将生成一个新的数据集，该数据集汇编了蜡样芽孢杆菌物种复合体的基因序列数据。这一组包括在土壤和植物表面具有有益作用的菌株，例如营养循环和阻断植物病原体，而遗传相似的菌株是人类、其他哺乳动物或昆虫的病原体。超越以前的研究，我们将测序具有重要生态功能的基因，例如参与攻击宿主防御的基因，以及通常用于MLSA研究的基本生物过程中所涉及的所谓“管家”基因。这将有助于对多样化的不同设想进行更全面的测试，特别是对具有不同生态属性的功能单位进行比较。研究结果将表明是否存在简单的多样性单位，或者多样化的模式是否不同，这取决于所考虑的基因组或多样性的哪个方面。这些结果将为细菌多样性的实际界定和关于多样性进化和物种性质的理论辩论建立新的方法和证据。