Department of Zoology, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
BMC Mol Biol. 2011 Aug 19;12:39. doi: 10.1186/1471-2199-12-39.
BACKGROUND: The vomeronasal organ (VNO) detects pheromones via two large families of vomeronasal receptors: vomeronasal receptor 1 (V1R) and vomeronasal receptor 2 (V2R). Both VRs have a common receptor activation cascade involving transient receptor potential channel, subfamily C, member 2 (TRPC2). RESULTS: We characterised the TRPC2 locus in a marsupial, the tammar wallaby (Macropus eugenii), and identified two independently regulated genes not previously recognised as distinct. 3'-located exons comprise bona fide TRPC2 whilst 5'-located exons, previously identified as part of TRPC2, comprise a distinct gene, which we term XNDR (XRCC1 N-terminal domain-related). The two genes show contrasting expression patterns in the tammar: TRPC2 is specifically expressed in adult and developing VNO, whereas XNDR is widely expressed in many tissues suggesting a non-VNO-specific role. Strong expression of TRPC2 was detected only after about day 30 post-partum, suggesting that the VNO may not be functional during early pouch life of the tammar. Similarly restricted expression of TRPC2 and widespread expression of XNDR was also detected in the platypus. Bioinformatic analysis of the genomes of a wide range of species suggests that the identity of XNDR and TRPC2 as distinct genes is conserved among vertebrates. Finally, we analysed the promoter of mammalian TRPC2 and identified a conserved binding site for NHLH1, a transcription factor previously implicated in VNO receptor neuron development. CONCLUSIONS: Two functionally distinct vertebrate genes-XNDR and TRPC2 - occupy a genomic locus that was previously defined as a single gene in the mouse. The former is widely expressed with a putative role in DNA repair, while the latter shows VNO-specific expression under the probable regulation of NHLH1.
背景:犁鼻器(VNO)通过两个大型犁鼻受体家族检测信息素:犁鼻受体 1(V1R)和犁鼻受体 2(V2R)。这两种 VR 都有一个共同的受体激活级联反应,涉及瞬时受体电位通道,亚家族 C,成员 2(TRPC2)。
结果:我们在有袋动物袋鼩(Macropus eugenii)中对 TRPC2 基因座进行了特征描述,并鉴定了两个以前未被识别为不同的独立调节基因。3'定位的外显子组成真正的 TRPC2,而 5'定位的外显子,以前被确定为 TRPC2 的一部分,组成一个不同的基因,我们称之为 XNDR(XRCC1 N-末端结构域相关)。这两个基因在袋鼩中表现出截然不同的表达模式:TRPC2 特异性表达于成年和发育中的犁鼻器,而 XNDR 广泛表达于许多组织中,提示其具有非犁鼻器特异性作用。仅在产后约 30 天后才检测到 TRPC2 的强烈表达,这表明在袋鼩的早期育儿袋生活中,犁鼻器可能不起作用。同样,在鸭嘴兽中也检测到了 TRPC2 的受限表达和 XNDR 的广泛表达。对广泛物种的基因组进行生物信息学分析表明,XNDR 和 TRPC2 作为不同基因的身份在脊椎动物中是保守的。最后,我们分析了哺乳动物 TRPC2 的启动子,并鉴定了 NHLH1 的一个保守结合位点,该转录因子先前被认为与犁鼻器受体神经元发育有关。
结论:两个功能上不同的脊椎动物基因——XNDR 和 TRPC2——占据了一个先前在小鼠中被定义为单个基因的基因组位点。前者广泛表达,具有潜在的 DNA 修复作用,而后者在 NHLH1 的可能调节下表现出犁鼻器特异性表达。
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