Regressive evolution of pigmentation in the Mexican cavefish, Astyanax mexicanus

描述(申请人提供)：大约10,000年前，一种住在河里的墨西哥四爪金枪鱼入侵了墨西哥中部阿布拉山地区的多个洞穴。这些与世隔绝的洞穴种群经历了形态特征的快速进化，如味蕾和牙齿的数量增加，色素和眼睛的丧失。形态特征的建设性进化可能与洞穴环境的适应优势有关(例如，对食物供应不足的反应增加了化学感觉)。性状的退化进化(例如，色素沉着的丧失)在进化、遗传和分子水平上知之甚少。这项研究提案的主要目的是通过研究海参洞穴种群中色素的丧失来了解退化进化的遗传结构。有多少基因参与了色素沉着丧失的进化？当这一性状在不同的种群(不同的洞穴)中平行进化时，是否使用相同的遗传途径来实现该性状？倒退的基因变化是结构性的还是规律性的？这些问题可以通过了解墨西哥冬虫夏草洞穴适应种群的色素损失来解决。我们以前的QTL分析和突变筛选表明，MC1R和OCA2都是Astianax中重要的着色基因。对MC1R和OCA2的调控以及它们在额外洞穴种群中的完整性进行更深入的分析，将允许对退化进化的本质进行更广泛的进化洞察。AIMS 1和AIMS 2将专注于确定表面墨西哥紫杉中MC1R和OCA2基因的最小、必要的调控序列。然后将对这些序列进行洞穴鱼种群的突变筛选。目标3将更广泛地解决哪些基因和哪些类型的遗传损伤导致色素沉着性状的退化进化。将与表层鱼和洞穴鱼进行新的遗传杂交，以筛选洞穴鱼种群中的显性突变。鉴定导致性状退化的显性突变将为形态性状的丧失提供有价值的见解。这项建议中涉及的问题与人类色素沉着缺陷直接相关，例如白化病(例如OMIM 203200)或红发/白皮肤患者患黑色素瘤的风险增加(OMIM 155555)。从这一提议中确定的调节性突变和显性突变将提供可以在人类患者中筛选的序列，目前尚未发现人类患者的突变。

DESCRIPTION (provided by applicant): Approximately 10,000 years ago, a river-dwelling tetra, Astyanax mexicanus invaded multiple caves in the Sierra de El Abra region of Central Mexico. These isolated cave populations underwent rapid evolution of morphological traits such as increased numbers of taste buds and teeth, and the loss of pigmentation and eyes. The constructive evolution of morphological traits can be associated with an adaptive advantage to the cave environment (e.g. increased chemical senses in response to low food supply). The regressive evolution of traits (e.g. loss of pigmentation) is poorly understood at the evolutionary, genetic and molecular levels. Understanding the genetic architecture of regressive evolution by studying the loss of pigmentation in Astyanax cave populations is the primary goal of this research proposal. How many genes are involved in evolution of pigmentation loss? When this trait evolves in parallel in different populations (different caves) are the same genetic pathways utilized to achieve the trait? Are regressive genetic changes structural or regulatory? These questions can be addressed by understanding pigmentation loss in Astyanax mexicanus cave-adapted populations. Our previous QTL analyses and mutation screening implicate both Mc1r and Oca2 as important pigmentation genes in Astyanax. Deeper analysis into the regulation of Mc1r and Oca2 as well as their integrity in additional cave populations will allow for broader evolutionary insights into the nature of regressive evolution. Aims 1 and 2 will focus on determining the minimal, necessary regulatory sequences for both the Mc1r and Oca2 genes in surface Astyanax mexicanus. These sequences will then be screened for mutations in cave fish populations. Aim 3 will more broadly address which genes and what types of genetic lesions lead to regressive evolution of pigmentation traits. A new genetic cross will be performed with surface and cave fish to screen for dominant mutations in the cave fish populations. Identification of dominant mutations leading to the regression of traits will lend valuable insight in to the loss of morphological traits. The questions addressed in this proposal are directly relevant to human pigmentation defects such as albinism (e.g. OMIM 203200) or red hair/fair skin patients with increased risk for melanoma (OMIM 155555). Regulatory mutations and dominant mutations identified from this proposal will provide sequences that could be screened in human patients, for whom no mutations have yet been identified.