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: 7789550
• 负责人: Jessica A Lehoczky
• 金额: $ 5.05万
• 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/7789550
• 关键词: Address; Albinism; Architecture; Chemicals; Defect; Environment; Evolution; Eye; Fishes; Food Supply; Genes; Genetic; Genetic Crosses; Goals; Hair; Human; Invaded; Lead; Lesion; Mexican; Mexico; Molecular Genetics; Mutation; Nature; 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10，000年前，一种居住在河流中的Tetra，Astyanax mexicanus入侵了墨西哥中部Sierra de El Abra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，例如味蕾和牙齿数量的增加，以及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，响应低食物供应的化学感觉增加）。在进化、遗传和分子水平上，对性状的退化进化（例如色素沉着的丧失）知之甚少。通过研究Astyanax洞穴种群中色素的丧失来了解回归进化的遗传结构是本研究提案的主要目标。有多少基因参与了色素沉着的演变？当这种特征在不同的种群（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种特征？退化性遗传变化是结构性的还是调节性的？这些问题可以通过了解在Astyanax mexicanus洞穴适应人口的色素沉着损失。我们先前的QTL分析和突变筛选暗示Mc 1 r和Oca 2作为重要的色素基因在Astyanax。对Mc 1 r和Oca 2的调节以及它们在其他洞穴种群中的完整性进行更深入的分析，将有助于对回归进化的性质进行更广泛的进化见解。目的1和2将集中在确定最小的，必要的调控序列的Mc 1 r和Oca 2基因在表面Astyanax墨西哥。然后将对这些序列在洞穴鱼类种群中进行突变筛查。目标3将更广泛地解决哪些基因和什么类型的遗传病变导致色素沉着性状的退行性进化。一个新的遗传杂交将与表面和洞穴鱼类进行筛选的洞穴鱼类种群中的显性突变。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。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）或具有黑色素瘤风险增加的红头发/浅色皮肤患者（OMIM 155555）。从该提议中鉴定的调控突变和显性突变将提供可以在人类患者中筛选的序列，对于这些患者，尚未鉴定出突变。