The repertoire of G-protein-coupled receptors in fully sequenced genomes

The repertoire of G-protein-coupled receptors in fully sequenced genomes
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DOI:
10.1124/mol.104.009001
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发表时间:
2005-05-01
影响因子:
3.6
通讯作者:
Schiöth, HB
Schiöth, HB
中科院分区:
医学3区
文献类型:
--
作者:
Fredriksson, R;Schiöth, HB

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G蛋白偶联受体(GPCRs)超家族是最大且研究最为深入的蛋白质家族之一。我们根据之前对人类GPCRs详细的系统发育分类中分组的GPCRs构建了隐马尔可夫模型,并添加了几个源自哺乳动物中未发现的受体的其他模型。我们利用这些模型搜索了13个基因组近乎完全测序的物种的整个基因扫描数据集。我们发现了5000多种独特的GPCRs,它们被分为15个主要群组,其中最大的视紫红质家族又被细分为13个亚类。结果表明,人类基因组中的主要家族,如谷氨酸、视紫红质、黏附、卷曲和分泌素家族,在线虫从脊索动物谱系分化之前就已经出现。此外,视紫红质家族的几个亚群在通向脊椎动物的谱系分化之前就已出现。我们还搜索了表达序列标签(EST)数据库,并确定了20000多条与GPCRs匹配的序列。尽管GPCRs通常占基因扫描预测结果的1% - 2%,但与GPCRs匹配的ESTs通常仅为0.01% - 0.001%,这表明大多数群组中的GPCRs表达水平较低。我们还提供了可搜索的数据集,可用于对GPCR家族进行注释和进一步的详细分析。这项研究对GPCRs家族和亚群的基因库扩展提供了广泛的概述。
The superfamily of G-protein-coupled receptors (GPCRs) is one of the largest and most studied families of proteins. We created Hidden Markov Models derived from sorted groups of GPCRs from our previous detailed phylogenetic classification of human GPCRs and added several other models derived from receptors not found in mammals. We used these models to search entire Genscan data sets from 13 species whose genomes are nearly completely sequenced. We found more than 5000 unique GPCRs that were divided into 15 main groups, and the largest one, the Rhodopsin family, was subdivided into 13 subclasses. The results show that the main families in the human genome, Glutamate, Rhodopsin, Adhesion, Frizzled, and Secretin, arose before the split of nematodes from the chordate lineage. Moreover, several of the subgroups of the Rhodopsin family arose before the split of the linage leading to vertebrates. We also searched expressed sequence tag ( EST) databases and identified more than 20,000 sequences that match GPCRs. Although the GPCRs represent typically 1 to 2% of the Genscan predictions, the ESTs that match GPCRs are typically only 0.01 to 0.001%, indicating that GPCRs in most of the groups are expressed at low levels. We also provide searchable data sets that may be used for annotation and further detailed analysis of the GPCR family. This study provides an extensive overview of the expansion of the gene repertoire for families and subgroups of GPCRs.