Evolution of Eye Regression in Cavefish

[9726561] Jeffery这个项目的目的是研究脊椎动物眼睛退化的遗传基础。作为模型系统，我们将使用Astyanax mexicanus鱼。由于以下原因，Astyanax系统非常适合研究眼睛变性。首先，在最后一个冰河时期，居住在地表的阿斯提亚纳克斯，它们有大眼睛，被隔离在洞穴里。这些穴居动物的后代后来失去了眼睛。地面和洞穴居住的Astyanax种群都已收集，目前可用于我实验室的研究。利用这些动物，我们将比较有眼睛和没有眼睛的动物的眼睛发育和退化。其次，在至少29个不同的洞穴中发现了无眼的阿斯蒂纳克斯，其中一些洞穴居民似乎已经独立失去了眼睛。因此，我们可以在可能不同的环境和进化条件下研究眼睛变性的遗传基础。第三，水面鱼和穴居鱼很容易在实验室培养，易于繁殖，具有互育性，而且水面鱼的眼睛结构与人类的眼睛结构相似。因此，Astyanax可以作为一种方便的实验系统来帮助了解人眼变性。这项提议有三个目标。首先，我们想要确定不同穴居Astyanax种群眼睛退化的进化史。这将通过比较地表和各种洞穴居民的DNA序列来完成。这些结果将回答在这些动物的进化史中眼睛退化是只出现过一次还是多次的问题。其次，我们想要在组织水平上确定眼睛变性的机制，即哪些眼部组织（晶状体、视网膜、角膜等）实际上发生了变性。这将通过检查变性眼组织中的细胞增殖和细胞死亡来完成。这些结果将使我们能够专注于在各种眼组织中起作用的特定基因。第三，我们想要确定与眼睛变性有关的基因。先前鉴定的眼睛基因的存在和功能将在地表和各种穴居Astyanax种群中进行研究。这个目的是为了确定眼睛变性的遗传基础。这个项目的意义跨越了进化生物学、发育生物学和视觉系统功能的领域。在进化生物学中，这个项目意义重大，因为它将确定在最后一个冰河时期可能发生过多次的进化变化的遗传基础。进化中的平行变化是否由相同或不同的机制和基因控制的开放性问题将得到解答。在发育生物学中，该项目具有重要意义，因为它将研究进化过程中发育变化的机制。目前对器官系统的发育在进化过程中是如何改变的了解很少，我们希望填补这一空白。最后，这个项目在视觉系统功能方面很重要，因为它解决了眼睛变性的遗传基础。阿斯顿鱼眼睛退化的一些机制和基因可能与人类视觉系统缺陷的机制和基因相同。

9726561 Jeffery The purpose of this project is to study the genetic basis of eye degeneration in a vertebrate animal. As a model system, we will use the fish Astyanax mexicanus. The Astyanax system is well suited for studying eye degeneration for the following reasons. First, during the last ice age, surface dwelling Astyanax, which have large eyes, were isolated in caves. The descendants of these cave-dwelling Astyanax subsequently lost their eyes. Both surface and cave dwelling Astyanax populations have been collected and are currently available for research in my laboratory. Using these animals we will compare eye development and degeneration in animals with and without eyes. Second, eyeless Astyanax are found in at least 29 different caves, and some of these cave dwelling populations appear to have lost their eyes independently. Therefore, we can study the genetic basis of eye degeneration under potentially different environmental and evolutionary conditions. Third, surface and cave dwelling Astyanax are easily cultured in the laboratory, breed readily, are inter-fertile, and the eye structure of the surface fish is similar to that found in humans. Thus, Astyanax can be used as a convenient experimental system to help understand human eye degeneration. This proposal has three objectives. First, we want to determine the evolutionary history of eye degeneration in different populations of cave dwelling Astyanax. This will be done by comparing DNA sequences of surface and various cave dwelling populations. The results will answer the question of whether eye degeneration appeared only once or many times during the evolutionary history of these animals. Second, we want to determine the mechanisms of eye degeneration at the tissue level, that is which eye tissues (lens, retina, cornea, etc.) actually degenerate. This will be done by examining cell proliferation and cell death in degenerating eye tissues. These results will allow us to focus on specific genes that function in vario us eye tissues. Third, we want to identify the genes involved in eye degeneration. The existence and function of previously identified eye genes will be studied in surface and various cave dwelling Astyanax populations. This objective is intended to establish the genetic basis of eye degeneration. The significance of this project spans the areas of evolutionary biology, developmental biology, and function of the visual system. In evolutionary biology, this project is significant because it will define the genetic basis of an evolutionary change which may have occurred multiple times during the last ice age. The open question of whether parallel changes in evolution are controlled by the same or different mechanisms and genes will be answered. In developmental biology, this project is significant because it will investigate the mechanisms underlying developmental changes during evolution. There is little current understanding of how development of organ systems is modified during evolution, and we expect to fill this void. Finally, this project is significant in regard to visual system function because it addresses the genetic basis of eye degeneration. Some of the mechanisms and genes underlying eye degeneration in Astyanax may be the same as those involved in visual system deficiencies in humans.