Evolution of melanopsin photoreceptors: Discovery and characterization of a new melanopsin in nonmammalian vertebrates
Evolution of melanopsin photoreceptors: Discovery and characterization of a new melanopsin in nonmammalian vertebrates
复制标题
DOI：
10.1371/journal.pbio.0040254
复制
发表时间：
2006-08-01
期刊：
影响因子：
9.8
通讯作者：
Lucas, Robert J.
中科院分区：
文献类型：
--
作者：
Bellingham, James;Chaurasia, Shyam S.;Lucas, Robert J.
在哺乳动物中，黑视素基因（Opn4）编码一种感觉光色素，这种色素是新发现的视网膜内光感受器的基础。自从黑视素基因首次在非洲爪蟾中被发现，并随后在人类和小鼠中被描述，黑视素基因已在所有脊椎动物类别中被描述。到目前为止，所有这些序列都被认为是一个同源基因的代表（尽管在硬骨鱼中有重复）。在这里，我们描述了在鱼类、鸟类和两栖动物基因组中发现的一种新的黑视素基因的功能特征，表明事实上，脊椎动物已经进化出两种完全不同的黑视素。在序列相似性、染色体定位和系统发育的基础上，我们确定了我们的新黑视蛋白是以前在哺乳动物中描述的黑视蛋白基因的真正同源物，并将该分组命名为Opn4m。相比之下，先前发表的非哺乳动物脊椎动物的黑视素基因代表了黑视素家族的一个独立分支，我们称之为Opn4x。对鸡、斑马鱼和非洲爪蟾的RT-PCR分析发现，Opn4m和Opn4x基因在已知的光敏组织（眼睛、大脑和皮肤）中都有表达。在第14天的鸡眼中，Opn4m mRNA存在于外核、内核和神经节细胞层的一部分细胞中，其中绝大多数细胞也表达Opn4x。重要的是，我们发现新的黑视素的一个代表（鸡的Opn4m）编码一种光感色素，能够在神经-2a细胞的异源表达下以光和视黄醛依赖的方式激活G蛋白信号级联反应。一项对脊椎动物基因组的全面计算机分析表明，虽然大多数脊椎动物物种同时具有Opn4m和Opn4x基因，但后者在真动物中缺失，可能还有有袋类哺乳动物，它们在进化过程中由于染色体重组而丢失。因此，我们的发现首次表明，非哺乳动物脊椎动物保留了两个完全独立的黑视素基因，而哺乳动物只有一个。这些数据提出了关于Opn4x和Opn4m色素之间功能差异的重要问题，保留这两种黑视素对大多数脊椎动物物种的相关适应性优势，以及缺乏Opn4x对哺乳动物生物学的影响。
In mammals, the melanopsin gene (Opn4) encodes a sensory photopigment that underpins newly discovered inner retinal photoreceptors. Since its first discovery in Xenopus laevis and subsequent description in humans and mice, melanopsin genes have been described in all vertebrate classes. Until now, all of these sequences have been considered representatives of a single orthologous gene ( albeit with duplications in the teleost fish). Here, we describe the discovery and functional characterisation of a new melanopsin gene in fish, bird, and amphibian genomes, demonstrating that, in fact, the vertebrates have evolved two quite separate melanopsins. On the basis of sequence similarity, chromosomal localisation, and phylogeny, we identify our new melanopsins as the true orthologs of the melanopsin gene previously described in mammals and term this grouping Opn4m. By contrast, the previously published melanopsin genes in nonmammalian vertebrates represent a separate branch of the melanopsin family which we term Opn4x. RT-PCR analysis in chicken, zebrafish, and Xenopus identifies expression of both Opn4m and Opn4x genes in tissues known to be photosensitive ( eye, brain, and skin). In the day-14 chicken eye, Opn4m mRNA is found in a subset of cells in the outer nuclear, inner nuclear, and ganglion cell layers, the vast majority of which also express Opn4x. Importantly, we show that a representative of the new melanopsins ( chicken Opn4m) encodes a photosensory pigment capable of activating G protein signalling cascades in a light- and retinaldehyde-dependent manner under heterologous expression in Neuro-2a cells. A comprehensive in silico analysis of vertebrate genomes indicates that while most vertebrate species have both Opn4m and Opn4x genes, the latter is absent from eutherian and, possibly, marsupial mammals, lost in the course of their evolution as a result of chromosomal reorganisation. Thus, our findings show for the first time that nonmammalian vertebrates retain two quite separate melanopsin genes, while mammals have just one. These data raise important questions regarding the functional differences between Opn4x and Opn4m pigments, the associated adaptive advantages for most vertebrate species in retaining both melanopsins, and the implications for mammalian biology of lacking Opn4x.