Comparative Analysis Of Completely Sequenced Genomes

完全测序的基因组的比较分析

• 批准号: 9160910
• 负责人: Eugene V Koonin
• 金额: $ 30.47万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9160910
• 关键词: Accounting; Adopted; Affect; Animals; Archaea; Bacteria; Bacteriophages; Beryllium; Clustered Regularly Interspaced Short Palindromic Repeats; Collection; Computing Methodologies; Data; Databases; Double Stranded DNA Virus; Double Stranded RNA Virus; Double-Stranded RNA; Elements; Eukaryota; Evolution; Family; Gene Frequency; Genes; Genetic Variation; Genome; Genome engineering; Genomics; Goals; Horizontal Gene Transfer; Immune system; Immunoglobulin Genes; Individual; Life; Methods; Minority; Mobile Genetic Elements; Modeling; Modification; Nature; Organism; Orthologous Gene; Phylogenetic Analysis; Phylogeny; Plant Roots; Plasmids; Probability; Process; Prokaryotic Cells; RNA Viruses; Recording of previous events; Relative (related person); Research; Retroelements; Role; Sampling; Single Stranded DNA Virus; Source; Surveys; System; Technology; Tectiviruses; Theoretical Studies; Trees; V(D)J Recombination; Vertebrates; Viral; Virion; Virus; adaptive immunity; comparative; ds-DNA; experience; fusion gene; genetic element; genome editing; genome sequencing; genome-wide; insight; long term memory; mathematical methods; mathematical model; paralogous gene; plasmid DNA; recombinase; tool; trend; virome

The rapidly growing database of completely and nearly completely sequenced genomes of bacteria, archaea, eukaryotes and viruses (several thousand genomes already available and many more in progress) creates both new opportunities and new challenges for genome research. During the last year, we performed a variety of studies that took advantage of the genomic information to establish fundamental principles of genome evolution. A comprehensive phylogenomic analysis of viruses infecting eukaryotic hosts and the related mobile elements was performed. Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangible clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order "Megavirales" that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources along with additional acquisitions of diverse genes. We developed a general scenario of evolution of adaptive immunity systems and possibly other genome manipulation machineries from mobile genetic elements. Adaptive immune systems in prokaryotes and animals give rise to long-term memory through modification of specific genomic loci, such as by insertion of foreign (viral or plasmid) DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci in prokaryotes and by V(D)J recombination of immunoglobulin genes in vertebrates. Strikingly, recombinases derived from unrelated mobile genetic elements have essential roles in both prokaryotic and vertebrate adaptive immune systems. Mobile elements, which are ubiquitous in cellular life forms, provide the only known, naturally evolved tools for genome engineering that are successfully adopted by both innate immune systems and genome-editing technologies. We performed a theoretical study of the evolution of bacterial and archaeal supergenomes. Because prokaryotic genomes experience a rapid flux of genes, selection may act at a higher level than an individual genome. We explore a quantitative model of the distributed genome whereby groups of genomes evolve by acquiring genes from a fixed reservoir which we denote as supergenome. Previous attempts to understand the nature of the supergenome treated genomes as random, independent collections of genes and assumed that the supergenome consists of a small number of homogeneous sub-reservoirs. Here we explore the consequences of relaxing both assumptions. We surveyed several methods for estimating the size and composition of the supergenome. The methods assumed that genomes were either random, independent samples of the supergenome or that they evolved from a common ancestor along a known tree via stochastic sampling from the reservoir. The reservoir was assumed to be either a collection of homogeneous sub-reservoirs or alternatively composed of genes with Gamma distributed gain probabilities. Empirical gene frequencies were used to either compute the likelihood of the data directly or first to reconstruct the history of gene gains and then compute the likelihood of the reconstructed numbers of gains. Supergenome size estimates using the empirical gene frequencies directly are not robust with respect to the choice of the model. By contrast, using the gene frequencies and the phylogenetic tree to reconstruct multiple gene gains produces reliable estimates of the supergenome size and indicates that a homogeneous supergenome is more consistent with the data than a supergenome with Gamma distributed gain probabilities. Taken together, these studies advance the existing understanding of the genome evolution in diverse life forms, in particular viruses and mobile elements, and provide new insights into general principles of genome evolution.

细菌，古细菌，真核生物和病毒（已经有几千个基因组，正在进行的更多基因组，正在进行的更多基因组）的完全且几乎完全测序的基因组的快速增长数据库为基因组研究带来了新的机会和新的挑战。在过去的一年中，我们进行了各种研究，利用基因组信息来建立基因组进化的基本原理。 对感染真核宿主的病毒和相关的移动元素进行了全面的系统基因分析。就身体丰度和遗传多样性而言，病毒和其他自私的遗传因素是生物圈中的主要实体。各种自私元素在所有细胞生命形式上都寄生。原核生物和真核生物之间不同类别的病毒的相对丰度截然不同。在原核生物中，绝大多数病毒具有双链（DS）DNA基因组，具有少数单链（SS）DNA病毒，并且只有有限的RNA病毒。相反，在真核生物中，尽管ssDNA和dsDNA病毒也很常见，但RNA病毒占了大多数病毒多样性。系统基因分析为主要类型的真核病毒的起源提供了切实的线索，尤其是它们在原核生物中的根源。具体而言，真核生物的正链RNA病毒的祖先基因组可能是从源自原核生物恢复和细菌的基因组装而来的，尽管该类别病毒的原始起源不能排除。不同的双链RNA病毒源自DSRNA噬菌体或阳性链RNA病毒。真核生物ssDNA病毒显然是通过原核滚动圆圈复制质粒和阳性链RNA病毒的基因融合而发展的。不同的真核DSDNA病毒家族似乎至少在两个独立的情况下起源于特定的噬菌体。 Polinton是最大的已知真核转座子，预计还形成了病毒颗粒，很可能是细菌构造病毒与几组真核DSDNA病毒之间的进化中间体，包括拟议的“巨型大型和巨大病毒的多样家庭）。令人惊讶的是，所有类别的真核病毒的演变似乎都涉及从不同来源得出的结构和复制基因模块之间的融合以及多种基因的其他获得。 我们开发了一种从移动遗传元素中的自适应免疫系统以及其他基因组操纵机器的演变的一般情况。 Adaptive immune systems in prokaryotes and animals give rise to long-term memory through modification of specific genomic loci, such as by insertion of foreign (viral or plasmid) DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci in prokaryotes and by V(D)J recombination of immunoglobulin genes in vertebrates.引人注目的是，来自无关的移动遗传元素衍生的重组酶在原核生物和脊椎动物适应性免疫系统中都具有重要作用。在细胞生命形式中无处不在的移动元素为基因组工程的唯一已知，自然发展的工具提供了由先天免疫系统和基因组编辑技术成功采用的基因组工程。 我们对细菌和古细菌超基因组的进化进行了理论研究。由于原核基因组经历了基因的快速通量，因此选择可以比单个基因组更高的水平起作用。我们探索了分布式基因组的定量模型，从而通过从固定储层中获取基因来进化，我们将其表示为超基因组。以前的尝试将超基因组治疗的基因组视为随机的，独立的基因集合的尝试，并假设超基因组由少量均质亚储库组成。在这里，我们探讨了放松这两个假设的后果。 我们调查了几种估计超基因组大小和组成的方法。该方法假设基因组是超基因组的随机，独立的样本，或者它们是通过储层的随机采样从已知树沿着已知树的共同祖先演变而来的。该储层被认为是同质亚库的集合，或者由具有伽马分布的增益概率的基因组成。经验基因频率被用来直接计算数据的可能性，或者首先要重建基因增长的历史，然后计算重建数量增长数量的可能性。使用经验基因频率直接相对于模型的选择，超基因组大小的估计并不强大。相比之下，使用基因频率和系统发育树来重建多个基因增益会产生对超基因组大小的可靠估计，并表明均质超基因组与数据比具有GAMMA分布的增益概率的超基因组更一致。 综上所述，这些研究提高了对各种生命形式的基因组进化的现有理解，尤其是病毒和移动元素，并为基因组进化的一般原理提供了新的见解。