Adaptive Evolution of Color Vision

描述(申请人提供)：动物已经多样化，并适应了地球上无数的栖息地和环境。我们研究的长期目标是在分子和功能水平上阐明驱动这些适应性变化的机制。我们计划使用VISION作为模型系统来实现这一目标。为了确定改变视觉色素最大吸收波长(MAX)的关键氨基酸(AA)变化，视觉科学家分析了“当代”色素。实验进化生物学家还操纵“当代”色素并推断过去。然而，忽视视觉色素的进化过程，既不能阐明视觉色素光谱调谐的分子基础，也不能阐明视觉色素的进化机制。幸运的是，光转导和进化生物学中的核心悬而未决的问题可以通过基因工程和操纵适当的“祖传色素”同时解决。在这里，我们建议阐明驱动脊椎动物RH2、SWS1和SWS2色素适应性进化的分子机制，它们的MAX分别为~450-530、~355-440和~400-460 nm。我们不仅通过确定视觉色素光谱调谐的分子基础来解决这个问题，而且还通过建立具有不同视觉色素集合的生物与其生态环境之间的关系来解决这个问题。对于每一组颜料，我们计划1)推断~15种祖传颜料的AA序列并对其进行工程处理并确定其；MAX，2)推断移动的AA变化；max，3)通过突变祖传颜料确定关键的AA变化，以及4)通过使用量子力学/分子力学(QM/MM)方法建立视觉颜料光谱调谐的普遍化学原理，这些方法已被证明是高效的。我们还将通过检查不同物种视觉色素的最大位移方向是否与生物体生态环境的变化相匹配来测试这些视觉色素适应性进化的可能性。为此，多个物种中具有可变MAX的三个色素组中的每一个都将根据它们的环境被划分为不同的类别，并测试其适应性进化的可能性。由于到目前为止所研究的几乎所有鱼类SWS1色素都是紫外线敏感的，我们也计划通过调查生活在0-200米深处并以小型鱼类为猎物且不需要紫外线视力来狩猎的鱼类，在不同的鱼类中寻找对紫色敏感的SWS1色素。考虑到SWS1颜料中发生的强烈的AA相互作用，我们还计划阐明各种关键的AA变化如何在其演变过程中积累，并了解UV颜料变得对紫罗兰敏感所需的化学结构前提条件，反之亦然。 公共卫生相关性：利用细胞/分子和量子化学方法，我们研究了不同脊椎动物及其祖先中视觉色素的结构-功能关系。视紫红质和其他视觉色素中不同的氨基酸变化导致不同程度的视觉色素错误折叠，已知会导致视网膜色素变性和其他视网膜营养不良。因此，我们的诱变实验和视觉色素的化学结构计算的结果一起提供了关于色觉缺陷和眼部疾病的遗传基础的基本信息。

DESCRIPTION (provided by applicant): Animals have diversified and adapted to fill the numerous habitats and environments on this earth. The long-term goal of our studies is to elucidate mechanisms that drive these adaptive changes at the molecular and functional levels. We plan to accomplish this goal using vision as a model system. To identify critical amino acid (AA) changes that modify the wavelengths of maximal absorption (;maxs) of visual pigments, vision scientists analyze "contemporary" pigments. Experimental evolutionary biologists also manipulate "contemporary" pigments and infer the past. However, by ignoring the evolutionary processes of visual pigments, neither the molecular basis of spectral tuning in visual pigments nor the evolutionary mechanisms of visual pigments can be elucidated. Fortunately, the central unanswered questions in phototransduction and evolutionary biology can be solved simultaneously by genetically engineering and manipulating proper "ancestral pigments." Here, we propose to elucidate the molecular mechanisms that drive adaptive evolution of RH2, SWS1, and SWS2 pigments in vertebrates, which have ;maxs of ~450-530, ~355-440, and ~400-460 nm, respectively. We approach the problem not only by determining the molecular basis of spectral tuning in visual pigments but also by establishing the relationships between organisms with different sets of visual pigments and their ecological environments. For each pigment group, we plan to 1) infer the AA sequences of ~15 ancestral pigments and engineer them and determine their ;maxs, 2) infer AA changes that shift the ;max, 3) identify the critical AA changes by mutating ancestral pigments, and 4) establish the universal chemical principle of the spectral tuning in visual pigments by using the quantum mechanical/molecular mechanical (QM/MM) methods, which have been proven to be highly effective. We shall also test the possibility of adaptive evolution of these visual pigments by examining whether the directions of the ;max-shifts of visual pigments in various species match with the changes in the organisms' ecological environments. For this purpose, each of the three pigment groups with variable ;maxs in multiple species will be classified into distinct classes according to their environments and tested for the possibility of adaptive evolution. Since virtually all fish SWS1 pigments examined to date are UV-sensitive, we also plan to search for violet-sensitive SWS1 pigments in different fishes, by surveying fishes that live at depths of 0-200 m and prey on small fishes and do not require UV vision for hunting. Considering the strong AA interactions that occur in SWS1 pigments, we also plan to elucidate how various critical AA changes could have accumulated during its evolution and learn the chemical structural preconditions required for UV pigments to become violet-sensitive and vice versa. PUBLIC HEALTH RELEVANCE: Using cell/molecular and quantum chemical methods, we study the structure-function relationships of visual pigments in various vertebrate species and their ancestors. Various levels of misfoldings of visual pigments induced by different amino acid changes in rhodopsins and other visual pigments are known to cause retinitis pigmentosa and other retinal dystrophies. Hence, the results obtained from our mutagenesis experiments and chemical structural computations of visual pigments together provide the fundamental information on the genetic bases of color vision defects and ocular diseases.