Different evolutionary processes shaped the mouse and human olfactory receptor gene families

Different evolutionary processes shaped the mouse and human olfactory receptor gene families
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DOI:
10.1093/hmg/11.5.535
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发表时间:
2002-03-01
影响因子:
3.5
通讯作者:
Trask, BJ
Trask, BJ
中科院分区:
生物学2区
文献类型:
--
作者:
Young, JM;Friedman, C;Trask, BJ

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我们报告了人类和小鼠嗅觉受体(OR)基因的全面比较分析。OR家族是已知的最大的哺乳动物基因家族。在估计的1500个小鼠OR中,我们识别出了93%的相似性,超过了先前的估计和人类OR的50%。只有20%是假基因,在小鼠中提供的功能性OR库是人类的三倍。由完整的人类OR编码的蛋白质比小鼠的那些蛋白质保守性低,其模式表明甚至一些明显完整的人类OR基因也可能编码非功能性蛋白质。小鼠OR聚集在46个基因组位置,而人类的OR分布更为分散。我们在大多数小鼠基因的同线人类位置发现了直系同源簇,这表明大多数OR基因簇早于灵长类动物与啮齿动物的分歧。然而,许多最近在两个基因组的本地或重复模糊一对一的orthopathic关系,从而复杂的跨物种推断OR-配体相互作用。局部复制是形成基因家族的主要力量。最近也发生了OR的染色体间重复,但在人类中比在小鼠中更频繁。除了澄清形成这个基因家族的进化力量,我们的研究提供了基础的转录调控和配体结合能力的OR基因家族的功能研究。
We report a comprehensive comparative analysis of human and mouse olfactory receptor (OR) genes. The OR family is the largest mammalian gene family known. We identify similar to93% of an estimated 1500 mouse ORs, exceeding previous estimates and the number of human ORs by 50%. Only 20% are pseudogenes, giving a functional OR repertoire in mice that is three times larger than that of human. The proteins encoded by intact human ORs are less highly conserved than those of mouse, in patterns that suggest that even some apparently intact human OR genes may encode non-functional proteins. Mouse ORs are clustered in 46 genomic locations, compared to a much more dispersed pattern in human. We find orthologous clusters at syntenic human locations for most mouse genes, indicating that most OR gene clusters predate primate-rodent divergence. However, many recent local OR duplications in both genomes obscure one-to-one orthologous relationships, thereby complicating cross-species inferences about OR-ligand interactions. Local duplications are the major force shaping the gene family. Recent interchromosomal duplications of ORs have also occurred, but much more frequently in human than in mouse. In addition to clarifying the evolutionary forces shaping this gene family, our study provides the basis for functional studies of the transcriptional regulation and ligand-binding capabilities of the OR gene family.