Comparative Analysis Of Completely Sequenced Genomes

完全测序的基因组的比较分析

• 批准号: 6988458
• 负责人: Eugene V Koonin
• 金额: --
• 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/6988458
• 关键词: Archaea; bacteria; biochemical evolution; bioinformatics; computer assisted sequence analysis; eukaryote; evolution; functional /structural genomics; genome; molecular biology information system; nucleic acid sequence; protein sequence; protein structure function; species difference

The rapidly growing database of completely sequenced genomes of bacteria, archaea and eukaryotes (approximately 200 genomes available by the end of 2004 and many more in progress) creates both new opportunities and new challenges for genome research. In order to take advantage of this information, we developed a system of Clusters of Orthologous Groups of proteins (COGs) from 30 completely sequenced genomes. This database is being continuously updated to incorporate newly appearing genomes. The COG approach allows nearly automatic functional annotation of 60-80% of the proteins encoded in each of the tested bacterial and archaeal genomes. During last year, the COG analysis was substantially expanded to include euakryotic genomes. Functional and evolutionary patterns in the recently constructed set of 5,873 clusters of predicted orthologs (eukaryotic orthologous groups or KOGs) from seven eukaryotic genomes: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe and Encephalitozoon cuniculi, were examined in detail. Conservation of KOGs through the phyletic range of eukaryotes strongly correlates with their functions and with the effect of gene knockout on the organism's viability. The approximately 40% of KOGs that are represented in six or seven species are enriched in proteins responsible for housekeeping functions, particularly translation and RNA processing. These conserved KOGs are often essential for survival and might approximate the minimal set of essential eukaryotic genes. The 131 single-member, pan-eukaryotic KOGs we identified were examined in detail. For around 20 that remained uncharacterized, functions were predicted by in-depth sequence analysis and examination of genomic context. Nearly all these proteins are subunits of known or predicted multiprotein complexes, in agreement with the balance hypothesis of evolution of gene copy number. Other KOGs show a variety of phyletic patterns, which points to major contributions of lineage-specific gene loss and the 'invention' of genes new to eukaryotic evolution. Examination of the sets of KOGs lost in individual lineages reveals co-elimination of functionally connected genes. Parsimonious scenarios of eukaryotic genome evolution and gene sets for ancestral eukaryotic forms were reconstructed. The gene set of the last common ancestor of the crown group consists of 3,413 KOGs and largely includes proteins involved in genome replication and expression, and central metabolism. Only 44% of the KOGs, mostly from the reconstructed gene set of the last common ancestor of the crown group, have detectable homologs in prokaryotes; the remainder apparently evolved via duplication with divergence and invention of new genes. CONCLUSIONS: The KOG analysis reveals a conserved core of largely essential eukaryotic genes as well as major diversification and innovation associated with evolution of eukaryotic genomes. The results provide quantitative support for major trends of eukaryotic evolution noticed previously at the qualitative level and a basis for detailed reconstruction of evolution of eukaryotic genomes and biology of ancestral forms.

细菌，古细菌和真核生物的完全测序基因组的快速增长的数据库（到2004年底，大约200个基因组可用，并且正在进行的更多基因组）为基因组研究带来了新的机会和新的机会。为了利用这些信息，我们从30个完全测序的基因组中开发了一个直系同源蛋白（COG）组的系统。该数据库正在不断更新以结合新出现的基因组。 COG方法允许在每个测试的细菌和古细菌基因组中编码的60-80％的蛋白质几乎自动功能注释。去年，COG分析大大扩展为包括欧洲蛋白酶基因组。 Functional and evolutionary patterns in the recently constructed set of 5,873 clusters of predicted orthologs (eukaryotic orthologous groups or KOGs) from seven eukaryotic genomes: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe and详细检查了脑静脉曲张。通过真核生物的植物范围来保护KOG与它们的功能以及基因敲除对生物体生存能力的影响密切相关。在六到七个物种中代表的KOG中，大约40％富含负责管家功能的蛋白质，尤其是翻译和RNA处理。这些保守的KOG通常对于生存至关重要，可能会近似最小的必需真核基因集。我们确定的131个单人核，泛核kog详细检查了。对于仍然没有特征的大约20个，通过深入的序列分析和基因组环境的检查来预测功能。几乎所有这些蛋白质都是已知或预测的多蛋白复合物的亚基，与基因拷贝数的进化的平衡假设一致。其他KOG显示了各种植物模式，这表明了谱系特异性基因丧失和真核进化新基因的“发明”的主要贡献。对单个谱系中丢失的KOG集合的检查表明，功能连接的基因的共灭态性。重建了真核生物基因组进化和基因集的简约场景。皇冠群的最后一个共同祖先的基因集由3,413个KOG组成，并且在很大程度上包括参与基因组复制和表达的蛋白质以及中央代谢。只有44％的KOG，主要来自皇冠群的最后一个共同祖先的重建基因集，在原核生物中具有可检测的同源物。其余的显然是通过复制和新基因发明而演变的。结论：KOG分析揭示了与真核基因组进化相关的主要必不可少的真核基因以及主要的多元化和创新的保守核心。该结果为先前在定性水平上注意到的真核进化的主要趋势提供了定量支持，并为真核基因组进化的详细重建和祖先形式的生物学重建提供了基础。