Molecular evolution of vision and visual pigments

视觉色素被光激活触发了眼睛感光器的感觉传导级联的第一步，最终导致神经信号传递到大脑。典型的脊椎动物视网膜有两种类型的光感受器，锥体用于白天的视觉，杆状体用于昏暗的光线。已知这些光感受器包含视觉转导级联的不同组成部分，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，爬行动物拥有自然界中已知的最多样化的视觉系统，特别是在视网膜的光感受器组成方面，它们经常失去两种光感受器中的任何一种。一个长期存在的理论认为，这可能是一种感光细胞类型向另一种不同寻常的进化转变的结果，这种过程在爬行动物之外很少见。这种现象最早是在夜行壁虎身上发现的，它们的视杆细胞被认为是从祖先的视锥细胞进化而来，保留了视锥细胞的视觉转导基因。我们的研究小组已经证明，类似的进化转变已经发生，但方向相反，在一种强烈的昼行性的袜带蛇身上。爬行动物的视网膜似乎能够在视网膜组成方面发生惊人的进化转变，但这些细胞背景下的差异对感光细胞的视觉转导机制（包括视觉色素）的影响尚不清楚，其起源仍然是一个谜。爬行动物的视觉系统为研究这些迷人的光感受器进化转变的起源和分子后果提供了难得的机会。我的研究项目使用创新的进化方法，包括实验和计算，通过研究生活在不同环境中的爬行动物和其他动物的适应性变化，来了解视觉色素功能的基本机制，这些环境中的光强度和可用光谱可能有很大不同。在这个研究计划中，我们有三个目标。(1)我们将通过实验研究进化转化的光感受器产生的视觉色素，比较蛇和壁虎的功能变化，并利用诱变方法确定两组中是否存在类似的功能变化机制。(2)我们将利用重建祖先鳞状动物视觉色素的测序、进化分析和实验分析相结合的方法来研究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，使我们能够快速有效地筛选数千种突变。我们将用它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.