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Genetic and Developmental Mechanisms of Evolutionary Innovations

进化创新的遗传和发育机制

基本信息

批准号：
8215918
负责人：
ARTYOM KOPP
金额：
$ 25.78万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-09 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8215918
关键词：
Adult Affect Affinity Animals Behavior Behavioral Binding Sites Biochemical Genetics Biological Biological Assay Biological Models Candidate Disease Gene Cell Differentiation process Chromosome Mapping Comb animal structure DNA DNA Sequence Data Development Drosophila genus Drug Design Evolution Experimental Models Female Gene Expression Gene Expression Regulation Gene Mutation Genes Genetic Crosses Genetic Drift Genome Genomics Goals Health Human Lead Link Modeling Molecular Molecular Genetics Molecular Profiling Morphology Motivation Mutation Natural Selections Nucleic Acid Regulatory Sequences Organ Output Pan Genus Pathway interactions Phenotype Phylogenetic Analysis Physiological Population Population Genetics Primates Prophylactic treatment Regulatory Pathway Research Resolution Sexual Development Shapes Site Structure Testing Tissues Transgenic Organisms Translating comparative developmental genetics gene function innovation male neurobiological mechanism novel programs sensory system sex systems research trait transcription factor

项目摘要

DESCRIPTION (provided by applicant): Morphological, physiological, and behavioral differences between humans and other primates are partly due to evolutionary innovations that arose in the human lineage. Understanding how and why these innovations evolved is a central motivation for sequencing the chimpanzee and other primate genomes. Interpreting the rapidly growing amounts of comparative sequence and gene expression data will require an integrated conceptual framework that connects molecular and phenotypic evolution. In this project, such framework will be developed in a Drosophila model, which allows genomic and population-genetic data to be combined with genetic crosses and experimental analyses of gene regulation and function. A powerful experimental model will be provided by a sex-specific morphological structure that originated and diversified recently in Drosophila evolution. The first goal of this project is to identify DNA sequence changes and population-genetic forces responsible for the origin and loss of regulatory interactions between genes that control the development of this structure. To accomplish this, biochemical, genetic, and comparative approaches will be combined to reconstruct the evolution of transcription factor binding sites in the regulatory region of a key gene that controls sex-specific differentiation, and examine the effects of natural selection on the sequence and affinity of these sites. The second goal is to identify the genetic and molecular changes responsible for the remodeling of a sex-specific developmental pathway on microevolutionary timescales. Comparative analysis of gene expression will be combined with genetic crosses and transgenic assays to understand how evolutionary changes in gene regulation affect cell differentiation and generate new morphogenetic pathways that shape adult morphology. These approaches will then be extended to a wider range of models to elucidate the genetic and developmental changes responsible for the origin of a novel sex-specific organ, and to test whether convergent morphological changes in different evolutionary lineages were caused by similar changes in development. The final goal of this project is to identify the genes and DNA sequence changes responsible for the recent origin of a unique sex-specific sensory system. This will open the way for understanding the molecular-genetic and neurobiological mechanisms of evolutionary changes in behavior. PUBLIC HEALTH RELEVANCE: The fundamental principle of sexual development - that sex-specific regulators act by modulating the output of other developmental pathways - is shared by all animals, including humans. Model system research that elucidates the molecular mechanisms and evolution of sexual differentiation will lead to a better understanding of the origin and development of sex-specific traits in humans, opening the way for designing drugs and prophylactic treatments that target male- or female-specific developmental pathways.

描述（由申请人提供）：人类和其他灵长类动物之间的形态，生理和行为差异部分是由于人类谱系中出现的进化创新。了解这些创新是如何以及为什么进化的，是对黑猩猩和其他灵长类动物基因组进行测序的核心动机。解释数量迅速增长的比较序列和基因表达数据将需要一个整合的概念框架，连接分子和表型进化。在本项目中，将在果蝇模型中开发这种框架，该模型允许将基因组和群体遗传数据与遗传杂交和基因调控和功能的实验分析相结合。一个强大的实验模型将提供性别特异性形态结构，起源和多样化最近在果蝇进化。该项目的第一个目标是确定DNA序列的变化和人口遗传力的起源和控制这种结构的发展基因之间的相互作用的监管损失负责。为了实现这一目标，生物化学，遗传学和比较的方法将结合起来，重建一个关键基因，控制性别特异性分化的调控区中的转录因子结合位点的进化，并检查自然选择对这些位点的序列和亲和力的影响。第二个目标是确定在微进化时间尺度上重塑性别特异性发育途径的遗传和分子变化。基因表达的比较分析将与遗传杂交和转基因检测相结合，以了解基因调控的进化变化如何影响细胞分化，并产生新的形态发生途径，形成成体形态。然后，这些方法将扩展到更广泛的模型，以阐明负责一个新的性别特异性器官的起源的遗传和发育变化，并测试是否收敛的形态学变化在不同的进化谱系是由类似的发展变化。该项目的最终目标是确定基因和DNA序列的变化，负责一个独特的性别特异性感觉系统的最近起源。这将为理解行为进化变化的分子遗传学和神经生物学机制开辟道路。公共卫生关系：性发育的基本原则--性别特异性调节器通过调节其他发育途径的输出来起作用--是所有动物包括人类所共有的。阐明性别分化的分子机制和进化的模型系统研究将导致更好地了解人类性别特异性特征的起源和发展，为设计针对男性或女性特异性发育途径的药物和预防性治疗开辟道路。