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、古生菌和真核生物基因组完全测序数据库的迅速增长（到2004年底大约有200个基因组，还有更多的基因组正在开发中）为基因组研究创造了新的机会，也提出了新的挑战。为了利用这一信息，我们开发了一个系统的集群的蛋白质（COG）从30个完全测序的基因组。该数据库正在不断更新，以纳入新出现的基因组。COG方法允许对每个测试的细菌和古细菌基因组中编码的60-80%的蛋白质进行几乎自动的功能注释。去年，COG分析大大扩展到包括真核生物基因组。最近构建的一组5,873簇预测的直向同源物（真核直向同源物组或KOG）的功能和进化模式，从七个真核生物基因组：秀丽隐杆线虫，黑腹果蝇，智人，拟南芥，酿酒酵母，裂殖酵母粟酒裂殖酵母和兔脑孢子虫，进行了详细检查。通过真核生物的系统发育范围的KOG的保护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。大约40%的KOG在六个或七个物种中代表，富含负责管家功能的蛋白质，特别是翻译和RNA加工。这些保守的KOG通常是生存所必需的，并且可能接近最小的必需真核基因集。详细检查了我们鉴定的131个单成员泛真核KOG。对于大约20个尚未鉴定的基因，通过深入的序列分析和基因组背景的检查预测了功能。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，与基因拷贝数进化的平衡假说一致。其他KOG显示了各种各样的系统模式，这表明了谱系特异性基因丢失和真核生物进化新基因的“发明”的主要贡献。对个体谱系中丢失的KOG组的检查揭示了功能相关基因的共同消除。真核生物基因组进化和基因组的祖先真核生物形式的简约方案进行了重建。冠群最后一个共同祖先的基因组由3，413个KOG组成，主要包括参与基因组复制和表达以及中心代谢的蛋白质。只有44%的KOG，主要来自冠群最后一个共同祖先的重建基因组，在原核生物中有可检测的同源物;其余的显然是通过复制与分歧和新基因的发明进化而来的。结论：KOG分析揭示了在很大程度上必需的真核基因的保守核心以及与真核基因组进化相关的主要多样化和创新。这些结果为以前在定性水平上注意到的真核生物进化的主要趋势提供了定量支持，并为真核生物基因组进化和祖先形式生物学的详细重建奠定了基础。