果蝇周期基因的哺乳动物同源物的昼夜节律振荡。

Circadian oscillation of a mammalian homologue of the Drosophila period gene.

作者信息

Tei H, Okamura H, Shigeyoshi Y, Fukuhara C, Ozawa R, Hirose M, Sakaki Y

机构信息

Human Genome Center, Institute of Medical Science, University of Tokyo, Japan.

出版信息

Nature. 1997 Oct 2;389(6650):512-6. doi: 10.1038/39086.

DOI:10.1038/39086

PMID:9333243

Abstract

Many biochemical, physiological and behavioural processes in organisms ranging from microorganisms to vertebrates exhibit circadian rhythms. In Drosophila, the gene period (per) is required for the circadian rhythms of locomotor activity and eclosion behaviour. Oscillation in the levels of per mRNA and Period (dPer) protein in the fly brain is thought to be responsible for the rhythmicity. However, no per homologues in animals other than insects have been identified. Here we identify the human and mouse genes (hPER and mPer, respectively) encoding PAS-domain (PAS, a dimerization domain present in Per, Amt and Sim)-containing polypeptides that are highly homologous to dPer. Besides this structural resemblance, mPer shows autonomous circadian oscillation in its expression in the suprachiasmaticnucleus, which is the primary circadian pacemaker in the mammalian brain. Clock, a mammalian clock gene encoding a PAS-containing polypeptide, has now been cloned: it is likely that the Per homologues dimerize with other molecule(s) such as Clock through PAS-PAS interaction in the circadian clock system.

摘要

从微生物到脊椎动物，生物体中的许多生物化学、生理和行为过程都呈现出昼夜节律。在果蝇中，周期基因（per）是运动活性和羽化行为昼夜节律所必需的。果蝇大脑中per mRNA和周期蛋白（dPer）水平的振荡被认为是节律性的原因。然而，除昆虫外，尚未在其他动物中鉴定出per同源物。在这里，我们鉴定出了人类和小鼠基因（分别为hPER和mPer），它们编码与dPer高度同源的含PAS结构域（PAS，存在于Per、Amt和Sim中的二聚化结构域）的多肽。除了这种结构相似性外，mPer在视交叉上核中的表达表现出自主昼夜振荡，视交叉上核是哺乳动物大脑中的主要昼夜起搏器。时钟基因（Clock），一种编码含PAS多肽的哺乳动物时钟基因，现已被克隆：在昼夜节律系统中，Per同源物可能通过PAS-PAS相互作用与其他分子（如Clock）形成二聚体。