Molecular Genetics of Sex-Specific Evolutionary Innovations

性别特异性进化创新的分子遗传学

• 批准号: 8627987
• 负责人: ARTYOM KOPP
• 金额: $ 28.23万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-16 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8627987
• 关键词: Address; Alternative Splicing; Animal Model; Animals; Appearance; Biological Assay; Cells; Comb animal structure; Complex; DNA Sequence; Development; Drosophila genus; Evolution; Female; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Recombination; Health; Hereditary Disease; Homeobox Genes; Homologous Gene; Human; Knowledge; Leg; Link; Modeling; Molecular; Molecular Genetics; Morphology; Mutation; Organ; Pattern; Predisposition; Process; Protein Isoforms; Proteins; Regulation; Regulatory Element; Relative (related person); Risk Factors; Sensory; Sequence Homologs; Site; Structure; Subgroup; Techniques; Technology; Testing; Tissues; Transgenic Organisms; Woman; Work; base; cell type; fly; gene replacement; genome sequencing; in vivo; innovation; intercellular communication; male; men; neuronal cell body; novel; public health relevance; sex; sexual dimorphism; theories; trait; transcription factor

DESCRIPTION (provided by applicant): Most animal species are sexually dimorphic, yet the features distinguishing males from females are different in every case. This simple observation implies that new sexual characters are gained, and old ones are lost, during the evolution of any animal lineage. The rapid turnover of sex-specific traits is as obvious in humans and their closest relatives as in other species, but the molecular mechanisms of this turnover are not well understood in any animal group. To address this critical gap in our knowledge, we will use the Drosophila model to identify the genetic changes responsible for the origin of new sexually dimorphic characters. Powerful transgenic technologies allow us to manipulate genome sequence and development in Drosophila in ways that are not possible in any other animal model. Recent work in our lab suggests that the origin of novel sex-specific traits is linked to evolutionary changes in the spatial regulation of doublesex (dsx), a transcription factor that controls sexual differentiation in most somatic tissues. This hypothesis represents a major departure from the previously accepted models, which ascribed the evolution of sexual dimorphism to changes in the target genes regulated by dsx. In this project, we will use a combination of several recently developed transgenic techniques to carry out a rigorous experimental test of the new model. We will focus on the "sex comb" - a strictly male-specific array of modified sensory organs that evolved recently within the genus Drosophila and shows dramatic diversity among closely related species. Our previous work has shown that sex comb development requires localized expression of dsx and sexually dimorphic expression of the homeotic gene Scr. In species that primitively lack sex combs, dsx expression is absent in the corresponding tissue while Scr expression is sexually monomorphic, suggesting that the origin of sex combs was caused by changes in dsx and Scr regulation. We have identified the DNA sequences (called "CREs") that control dsx and Scr expression, and will now characterize the functional impact of the evolutionary changes in these sequences. First, we will compare the regulatory activities of CREs from species with different sex comb morphology and species that lack sex combs, and test whether the origin of the sex comb coincided with the origin of new CREs that drive gene expression in the cells that give rise to this structure. Second, we will replace the dsx and Scr CREs in D. melanogaster with homologous DNA sequences from species with different sex comb morphology and species that lack sex combs, and test whether these replacements are sufficient to eliminate the sex comb or change its appearance. Finally, we will extend this work to other sex-specific structures that evolved independently in distantly related species in order to test the generality of the new model of evolutionary change. A direct experimental confirmation of this model will help explain the origin of sexual dimorphism in all animals.

描述（由申请人提供）：大多数动物物种都是两性二态的，但区分雄性和雌性的特征在每种情况下都不同。这个简单的观察表明，在任何动物谱系的进化过程中，都会获得新的性特征，而旧的性特征会消失。性别特异性特征的快速转变在人类及其近亲中和其他物种中一样明显，但这种转变的分子机制在任何动物群体中尚不清楚。为了解决我们知识中的这一关键差距，我们将使用果蝇模型来识别导致新的两性性状起源的遗传变化。强大的转基因技术使我们能够以任何其他动物模型不可能的方式操纵果蝇的基因组序列和发育。我们实验室最近的工作表明，新的性别特异性特征的起源与双性（dsx）空间调节的进化变化有关，双性是一种控制大多数体细胞组织性别分化的转录因子。这一假说与之前接受的模型有很大不同，之前的模型将性二态性的进化归因于 dsx 调节的靶基因的变化。在这个项目中，我们将结合几种最近开发的转基因技术对新模型进行严格的实验测试。我们将重点关注“性梳”——一系列严格意义上的雄性特有的改良感觉器官，它最近在果蝇属中进化出来，并在密切相关的物种之间表现出巨大的多样性。我们之前的工作表明，性梳发育需要 dsx 的局部表达和同源异型基因 Scr 的性二态性表达。在原始缺乏性梳的物种中，相应组织中不存在 dsx 表达，而 Scr 表达是性单态的，这表明性梳的起源是由 dsx 和 Scr 调节的变化引起的。我们已经鉴定了控制 dsx 和 Scr 表达的 DNA 序列（称为“CRE”），现在将描述这些序列进化变化的功能影响。首先，我们将比较具有不同性别梳形态的物种和缺乏性别梳的物种的CRE的调节活性，并测试性别梳的起源是否与新的CRE的起源一致，新的CRE在产生这种结构的细胞中驱动基因表达。其次，我们将用具有不同性梳形态的物种和缺乏性梳的物种的同源DNA序列替换黑腹果蝇中的dsx和Scr CRE，并测试这些替换是否足以消除性梳或改变其外观。最后，我们将这项工作扩展到远缘物种中独立进化的其他性别特异性结构，以测试进化变化新模型的普遍性。该模型的直接实验证实将有助于解释所有动物性别二态性的起源。