Bjarnadóttir Thóra K, Gloriam David E, Hellstrand Sofia H, Kristiansson Helena, Fredriksson Robert, Schiöth Helgi B
Department of Neuroscience, Biomedical Center, Uppsala University, Box 593, 751 24 Uppsala, Sweden.
Genomics. 2006 Sep;88(3):263-73. doi: 10.1016/j.ygeno.2006.04.001. Epub 2006 Jun 6.
Understanding differences in the repertoire of orthologous gene pairs is vital for interpretation of pharmacological and physiological experiments if conclusions are conveyed between species. Here we present a comprehensive dataset for G protein-coupled receptors (GPCRs) in both human and mouse with a phylogenetic road map. We performed systematic searches applying several search tools such as BLAST, BLAT, and Hidden Markov models and searches in literature data. We aimed to gather a full-length version of each human or mouse GPCR in only one copy referring to a single chromosomal position. Moreover, we performed detailed phylogenetic analysis of the transmembrane regions of the receptors to establish accurate orthologous pairs. The results show the identity of 495 mouse and 400 human functional nonolfactory GPCRs. Overall, 329 of the receptors are found in one-to-one orthologous pairs, while 119 mouse and 31 human receptors originate from species-specific expansions or deletions. The average percentage similarity of the orthologue pairs is 85%, while it varies between the main GRAFS families from an average of 59 to 94%. The orthologous pairs for the lipid-binding GPCRs had the lowest levels of conservation, while the biogenic amines had highest levels of conservation. Moreover, we searched for expressed sequence tags (ESTs) and identified more than 17,000 ESTs matching GPCRs in mouse and human, providing information about their expression patterns. On the whole, this is the most comprehensive study of the gene repertoire that codes for human and mouse GPCRs. The datasets are available for downloading.
如果要在不同物种间传达实验结论，那么了解直系同源基因对库的差异对于药理学和生理学实验的解读至关重要。在此，我们提供了一个包含人类和小鼠G蛋白偶联受体（GPCR）的综合数据集，并绘制了系统发育路线图。我们使用了多种搜索工具，如BLAST、BLAT和隐马尔可夫模型进行系统搜索，并在文献数据中进行检索。我们的目标是仅以单拷贝形式获取每个人类或小鼠GPCR的全长版本，并将其定位到单个染色体位置。此外，我们对受体的跨膜区域进行了详细的系统发育分析，以确定准确的直系同源对。结果显示，小鼠有495个和人类有400个功能性非嗅觉GPCR。总体而言，329个受体以一对一的直系同源对形式存在，而119个小鼠受体和31个人类受体则源于物种特异性的扩增或缺失。直系同源对的平均相似百分比为85%，而在主要的GRAFS家族之间，这一比例从平均59%到94%不等。脂质结合型GPCR的直系同源对保守水平最低，而生物胺的保守水平最高。此外，我们搜索了表达序列标签（EST），并在小鼠和人类中鉴定出超过17000个与GPCR匹配的EST，提供了有关它们表达模式的信息。总体而言，这是对编码人类和小鼠GPCR的基因库最全面的研究。这些数据集可供下载。
