Molecular evolution of vision and visual pigments

由光激活的视觉色素触发了眼睛光感受器感觉转导的第一步，最终导致神经信号到达大脑。典型的脊椎动物视网膜有两种类型的光感受器，视锥用于白天的视觉，视杆用于昏暗的光线。众所周知，这些光感受器含有视觉转导级联的不同成分，包括视杆和视锥视觉色素，这被认为是两者之间一些生理差异的基础。在脊椎动物中，爬行动物拥有一些在自然界中已知的最多样化的视觉系统，特别是就其视网膜的光感受器组成而言，两种光感受器类型中的任何一种经常丢失。一种由来已久的理论认为，这可能是一种感光细胞类型向另一种感光细胞类型的不寻常进化转化的结果，这一过程在爬行动物之外是罕见的。这首先是在夜间活动的壁虎中发现的，在夜间壁虎中，杆状细胞被认为是从祖先的锥体进化而来的，保留了锥体视觉传导基因。我们的团队已经证明，在一种昼夜活动强烈的吊袜蛇物种中，也发生了类似的进化转变，但方向相反。爬行动物的视网膜似乎能够在视网膜组成方面进行显著的进化转化，但这些细胞环境的差异对光感受器细胞的视觉转导机制(包括视觉色素)的影响尚不清楚，其起源仍是一个谜。爬行动物的视觉系统是研究这些令人着迷的进化光感受器转变的起源和分子后果的难得机会。我的研究项目使用创新的进化方法，包括实验和计算方法，通过研究爬行动物和其他生活在不同环境中的动物的适应性变化来了解视觉色素功能的基本机制，在不同的环境中，光强度和可用光谱可能截然不同。在这个研究方案中，我们有三个目标。(1)我们将对进化转化的光感受器产生的视觉色素进行实验研究，比较蛇和壁虎的功能变化，并使用突变方法来确定这两组动物的功能变化是否存在类似的机制。(2)我们将结合测序、进化分析和重建的祖先鳞状动物视觉色素的实验分析来探索爬行动物视网膜中光感受器转化的进化起源。(3)最后，我的团队最近开发了第一个高通量的视觉色素激活试验，它使我们能够快速有效地筛选数千个突变。我们将利用这一点来筛选视觉色素的突变，并更好地了解功能不同方面的权衡。

Visual pigment activation by light triggers the first step of the sensory transduction cascade in photoreceptors of the eye that ultimately results in a neural signal to the brain. Typical vertebrate retinas have two types of photoreceptors, cones for vision during the day, and rods for dim light. These photoreceptors are known to contain different components of the visual transduction cascade, including rod and cone visual pigments, which are thought to underlie some of the physiological differences between the two. Among vertebrates, reptiles possess some of the most diverse visual systems in known in nature, especially in terms of the photoreceptor composition of their retinas, with frequent losses of either of the two photoreceptor types. A longstanding theory postulated that this might be the result of unusual evolutionary transformations from one photoreceptor cell type into another, a process rare outside of reptiles. This was first discovered in nocturnal geckos, in which the rods are thought to have evolved from ancestral cones, retaining cone visual transduction genes. Our group has demonstrated that a similar evolutionary transformation has taken place, but in the opposite direction, in a strongly diurnal species of garter snake. Reptilian retinas appear to be capable of striking evolutionary transformations in terms of retinal composition, but the consequence of these differences in cellular context for the visual transduction machinery of the photoreceptor cell, including the visual pigments, is not well understood, and its origins remain shrouded in mystery. Reptilian visual systems represent a rare opportunity to study the origins and molecular consequences of these fascinating evolutionary photoreceptor transformations. My research program uses innovative evolutionary approaches, both experimental and computational, to understand fundamental mechanisms of visual pigment function by studying adaptive variation found in reptiles and other animals living in diverse environments where light intensities and available spectrum can be dramatically different. In this research proposal, we have three objectives. (1) We will experimentally investigate visual pigments from evolutionary transformed photoreceptors, comparing the functional shifts in snakes and geckos, and use mutagenesis approaches to determine if similar mechanisms underlie shifts in function in the two groups. (2) We will use a combination of sequencing, evolutionary analysis, and experimental assays of reconstructed ancestral squamate visual pigments to investigate the evolutionary origins of photoreceptor transformations in reptilian retinas. (3) Finally, my group has recently developed the first high-throughput assay of visual pigment activation, which allows us to rapidly screen thousands of mutations efficiently. We will use this to screen mutations in visual pigments, and better understand tradeoffs in different aspects of function.