Gene duplication in the evolution of novel phenotypes and human disease

新表型和人类疾病进化中的基因复制

• 批准号: 8536143
• 负责人: Raquel Assis
• 金额: $ 2.44万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-16 至 2014-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536143
• 关键词: Address; Algorithms; Alzheimer' s Disease; Animal Model; Biological Preservation; Data; Disabled Persons; Disease; Drosophila genus; Evolution; Frequencies; Gene Duplication; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic Research; Genome; Genomics; Heart Diseases; Individual; Knowledge; Lead; Light; Little' s Disease; Maintenance; Malignant Neoplasms; Maps; Measures; Molecular Profiling; Mutation; Organism; Partner in relationship; Phenotype; Play; Population; Population Sizes; Prevalence; Process; Proxy; Reading; Relative (related person); Research; Role; Sister; Source; Tissues; base; comparative; driving force; duplicate genes; genome analysis; genome sequencing; handicapping condition; human disease; innovation; novel; trait

DESCRIPTION (provided by applicant): Gene duplication is a key source of genetic novelty, which in the best case leads to the acquisition of advantageous phenotypes, and in the worst results in disease. Functional duplicate genes can be maintained in the genome via three distinct processes: 1) the acquisition of a novel function in one copy (neofunctionalization), 2) the division of ancestral functions among copies (subfunctionalization), or 3) the preservation of ancestral functions in all copies (conservation). Despite the importance of gene duplications in both evolution and disease, little is known about the relative frequencies or mechanisms of each of these processes. To address these questions, this proposal will utilize complementary high-throughput experimental and computational approaches to investigate the correlated sequence and expression evolution of duplicate genes in three closely-related species of Drosophila. In particular, this project is subdivided into three specific aims. First, it will identify recent gen duplications via comparative genome analysis of three closely-related species of Drosophila. Second, it will use gene expression as a proxy for function to disentangle the processes of neofunctionalization, subfunctionalization, and conservation in the maintenance of young duplicate genes in Drosophila. Third, from intra-species polymorphism data, it will infer the evolutionary forces driving each of these processes. Due to the central role Drosophila has played as a model organism in genetic research, findings from this study will likely be applicable to a wide range of organisms, enhancing our understanding of both the evolution of novel phenotypes and the genetic basis of duplication-associated human diseases.

描述（由申请人提供）：基因复制是遗传新奇的关键来源，其在最好的情况下导致获得有利的表型，而在最坏的情况下导致疾病。功能性重复基因可以通过三种不同的过程在基因组中维持：1）在一个拷贝中获得新功能（新功能化），2）在拷贝之间划分祖先功能（亚功能化），或3）在所有拷贝中保留祖先功能（保守）。尽管基因复制在进化和疾病中都很重要，但人们对这些过程的相对频率或机制知之甚少。为了解决这些问题，该提案将利用互补的高通量实验和计算方法来研究果蝇三个密切相关物种中重复基因的相关序列和表达进化。该项目具体分为三个目标。首先，它将通过对三种密切相关的果蝇物种进行比较基因组分析来确定最近的基因重复。第二，它将使用基因表达作为功能的代理，以解开新功能化，亚功能化，并在维护年轻的果蝇重复基因的保护过程。第三，从物种内多态性数据，它将推断驱动这些过程的进化力量。由于果蝇在遗传学研究中作为模式生物发挥了核心作用，这项研究的结果可能适用于广泛的生物体，增强了我们对新表型进化和复制相关人类疾病遗传基础的理解。