Molecular Genetics of Sex-Specific Evolutionary Innovations

性别特异性进化创新的分子遗传学

基本信息

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
项目类别：
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

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

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项目摘要

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）：大多数动物都是性二态性的，但是在每种情况下，将男性与雌性区分开的特征都是不同的。这种简单的观察表明，在任何动物谱系的演变过程中，都会获得新的性特征，而旧的性格也丢失了。在人类及其最接近的亲戚中，性别特异性特异性的快速营业额与其他物种一样明显，但是在任何动物群体中，这种营业额的分子机制都不被很好地理解。为了解决我们知识的这一关键差距，我们将使用果蝇模型来确定导致新的性二态特征起源的遗传变化。强大的转基因技术使我们能够以任何其他动物模型都无法使用果蝇的基因组序列和发育来操纵基因组序列和发展。我们实验室中的最新工作表明，新型性别特异性性状的起源与Doublesex（DSX）的空间调节的进化变化有关，Doublesex（DSX）是控制大多数体细胞组织中性别分化的转录因子。该假设代表了与先前接受的模型的主要不同，该模型将性二态性的演变归因于DSX调节的目标基因的变化。在这个项目中，我们将结合几种最近开发的转基因技术来对新模型进行严格的实验测试。我们将重点关注“性梳子” - 严格的男性特异性感觉器官阵列，最近在果蝇属内进化，并在密切相关的物种之间显示出巨大的多样性。我们以前的工作表明，性梳子的发展需要DSX的局部表达和同源基因SCR的性二态表达。在原始缺乏性梳子的物种中，在相应的组织中不存在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。我们已经确定了控制DSX和SCR表达的DNA序列（称为“ CRES”），现在将表征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梳形态和缺乏性梳子的物种的CRE的调节活性，并测试性梳子的起源是否与在细胞中驱动基因表达的新CRE的起源相吻合，从而引起了这种结构。其次，我们将用具有不同性梳形态的物种和缺乏性梳子的物种的同源DNA序列代替DSX和SCR CRE，并测试这些替代品是否足以消除性梳子或改变其外观。最后，我们将将这项工作扩展到其他特定于性别的结构，这些结构是在遥远相关的物种中独立进化的，以测试新的进化变化模型的一般性。对该模型的直接实验确认将有助于解释所有动物中性二态性的起源。