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、古生物和真核生物全序列基因组数据库的迅速增长(到2004年底约有200个基因组可用，还有许多正在进行中)为基因组研究创造了新的机遇和新的挑战。为了利用这一信息，我们从30个完全测序的基因组中开发了一个由同源蛋白质组(COG)组成的系统。这个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。在去年，COG的分析大大扩展到包括真核细胞基因组。最近构建的一组5873个预测的同源物(真核同源组或KOG)的功能和进化模式被详细研究了，这些同源物来自七个真核基因组：秀丽线虫、黑腹果蝇、智人、拟南芥、酿酒酵母、庞氏裂殖酵母和楔脑虫。在真核生物的系统发育范围内，KOG的保守性与它们的功能以及基因敲除对生物体生存的影响密切相关。在6到7个物种中，大约40%的KOG富含负责家务功能的蛋白质，特别是翻译和RNA加工。这些保守的KOG通常是生存所必需的，可能接近最小的必需真核基因集。对我们鉴定的131个单成员、泛真核KOG进行了详细的研究。对于仍未确定特征的约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体的亚基，这与基因拷贝数进化的平衡假说一致。其他的KOG显示了各种各样的系统模式，这表明了谱系特有的基因丢失和真核生物进化中新基因的“发明”的主要贡献。对个体谱系中丢失的KOG集合的检查显示，功能相关的基因共同消除。重建了真核生物基因组进化的简约场景和祖先真核生物形式的基因集。冠群最后一个共同祖先的基因集由3,413个KOG组成，主要包括参与基因组复制和表达以及中央代谢的蛋白质。只有44%的KOG在原核生物中有可检测到的同源物；其余的显然是通过复制和发散以及新基因的发明而进化的，这些KOG大多来自于冠群最后一个共同祖先的重建基因集。结论：KOG分析揭示了主要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性和创新。这些结果为定性水平上观察到的真核生物进化的主要趋势提供了定量支持，并为详细重建真核生物基因组进化和祖先形式生物学奠定了基础。