Large-scale taxonomic profiling of eukaryotic model organisms: A comparison of orthologous proteins encoded by the human, fly, nematode, and yeast genomes
Large-scale taxonomic profiling of eukaryotic model organisms: A comparison of orthologous proteins encoded by the human, fly, nematode, and yeast genomes
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DOI：
10.1101/gr.8.6.590
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发表时间：
1998-06-01
期刊：
影响因子：
7
通讯作者：
Liu, LX
中科院分区：
文献类型：
--
作者：
Mushegian, AR;Garey, JR;Liu, LX
人类和模型生物（包括酿酒酵母、线虫秀丽隐杆线虫和果蝇）之间 DNA 和蛋白质序列的比较是有关正常和疾病状态下人类基因和蛋白质功能的重要信息来源。有关跨物种序列比较的重要问题仍未得到解答，包括（1）人类和各种模型共享的代谢、信号传导和调节途径的比例有机体； (2)基于序列同源性的函数推理的有效性。我们通过分析人类、果蝇、线虫和酵母基因组中直向同源蛋白质编码基因的可用部分来解决这些问题，并应用严格的标准来区分候选直向同源和旁系同源蛋白质。 42 个四联蛋白可以被鉴定为候选直向同源物，24 个果蝇蛋白序列比相应的线虫蛋白更类似于它们的人类直向同源物。对该数据集中的序列替换和进化距离的分析表明，大多数线虫基因比果蝇基因进化得更快，这表明不平等的进化速率可能导致与人类蛋白质序列相似性的差异。果蝇蛋白质的可用部分似乎缺乏许多蛋白质家族和结构域的代表，反映出该物种的基因组数据相对缺乏。
Comparisons of DNA and protein sequences between humans and model organisms, including the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, and the Fruit fly Drosophila melanogaster, are a significant source of information about the function of human genes and proteins in both normal and disease states, Important questions regarding cross-species sequence comparison remain unanswered, including (1) the fraction of the metabolic, signaling, and regulatory pathways that is shared by humans and the various model organisms; and (2) the validity of functional inferences based on sequence homology. We addressed these questions by analyzing the available fractions of human, fly, nematode, and yeast genomes for orthologous protein-coding genes, applying strict criteria to distinguish between candidate orthologous and paralogous proteins. Forty-two quartets of proteins could be identified as candidate orthologs, Twenty-four Drosophila protein sequences were more similar to their human orthologs than the corresponding nematode proteins. Analysis of sequence substitutions and evolutionary distances in this data set revealed that most C. elegans genes are evolving more rapidly than Drosophila genes, suggesting that unequal evolutionary rates may contribute to the differences in similarity to human protein sequences. The available fraction of Drosophila proteins appears to lack representatives of many protein families and domains, reflecting the relative paucity of genomic data From this species.