Regressive evolution of pigmentation in the Mexican cavefish, Astyanax mexicanus

墨西哥穴居鱼 Astyanax mexicanus 色素沉着的退化进化

• 批准号: 7480665
• 负责人: Jessica A Lehoczky
• 金额: $ 4.48万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480665
• 关键词: Address; Albinism; Architecture; Chemicals; Defect; Depth; Disease regression; Environment; Evolution; Eye; Fishes; Food Supply; Genes; Genetic; Genetic Crosses; Goals; Hair; Human; Invaded; Lead; Lesion; Mexican; Mexico; Molecular Genetics; Mutation; Nature; Numbers; Online Mendelian Inheritance In Man; Pathway interactions; Patients; Pigmentation physiologic function; Population; Quantitative Trait Loci; Regulation; Research Proposals; Risk; Rivers; Screening procedure; Skin; Surface; Taste Buds; Tooth Loss; insight; melanoma; response; trait

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.

描述（由申请人提供）：大约1万年前，一种居住在河流中的四目动物，Astyanax mexicanus入侵了墨西哥中部的Sierra de El Abra地区的多个洞穴。这些孤立的洞穴种群经历了形态特征的快速进化，如味蕾和牙齿数量的增加，色素沉着和眼睛的丧失。形态特征的建设性进化可能与洞穴环境的适应性优势有关（例如，对低食物供应的反应增加了化学感觉）。在进化、遗传和分子水平上，对性状（如色素沉着丧失）的退化进化知之甚少。通过研究Astyanax洞穴种群中色素沉着的丧失来了解退化进化的遗传结构是本研究计划的主要目标。有多少基因参与色素丧失的进化？当这一特性在不同的种群（不同的洞穴）中平行进化时，是否利用了相同的遗传途径来实现这一特性？退化的基因变化是结构性的还是规范性的？这些问题可以通过了解适应洞穴的墨西哥Astyanax种群的色素沉着丧失来解决。我们之前的QTL分析和突变筛选表明Mc1r和Oca2都是Astyanax重要的色素沉着基因。对Mc1r和Oca2的调控以及它们在其他洞穴种群中的完整性进行更深入的分析，将使我们对退化进化的本质有更广泛的了解。目的1和2将集中于确定墨西哥Astyanax表面Mc1r和Oca2基因的最小的、必要的调控序列。这些序列将在洞穴鱼类种群中进行突变筛选。目标3将更广泛地讨论哪些基因和哪些类型的遗传病变导致色素沉着特征的退化进化。一项新的基因杂交将在水面鱼和洞穴鱼之间进行，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学性状的丧失提供有价值的见解。本提案中解决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）或患黑色素瘤风险增加的红发/白皙皮肤患者（OMIM 155555）。从该提案中确定的调节突变和显性突变将提供可在尚未确定突变的人类患者中筛选的序列。