Molecular Genetics of Sex-Specific Evolutionary Innovations

描述(申请人提供)：大多数动物物种是两性异形的，但区别雄性和雌性的特征在每一种情况下都不同。这一简单的观察表明，在任何动物谱系的进化过程中，都会获得新的性别特征，而旧的性别特征则会消失。与其他物种一样，人类及其近亲的性别特异性特征的快速变化也很明显，但这种变化的分子机制在任何动物群体中都不是很清楚。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确定导致新的性别二型性特征起源的基因变化。强大的转基因技术使我们能够操纵果蝇的基因组序列和发育，这在任何其他动物模型中都是不可能的。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性别空间调控的进化变化有关，双性性转录因子是一种在大多数体细胞组织中控制性分化的转录因子。这一假说与以前被接受的模型有很大不同，以前的模型将性别二型性的进化归因于受DSX调控的目标基因的变化。在这个项目中，我们将结合最近开发的几种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”--一种严格针对男性的改良感觉器官阵列，它最近在果蝇属内进化，并在密切相关的物种中显示出戏剧性的多样性。我们以前的工作表明，性梳子的发育需要dsx的局部表达和同源异型基因SCR的性别二态表达。在原始缺乏性梳的物种中，相应的组织中不存在DSX的表达，而SCR的表达是性别单态的，这表明性梳的起源是由DSX和SCR调控的变化引起的。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中进化变化的功能影响。首先，我们将比较具有不同性别梳子形态的物种和缺乏性别梳子的物种的CRE的调节活性，并测试性别梳子的起源是否与驱动产生这种结构的细胞中的基因表达的新的CRE的起源一致。其次，我们将用具有不同性别梳形态的物种和缺乏性别梳的物种的同源DNA序列来替换黑腹金丝雀中的DSX和SCR Cres，并测试这些替换是否足以消除性别梳或改变其外观。最后，我们将把这项工作扩展到其他在远亲物种中独立进化的性别特有结构，以测试新的进化变化模式的普遍性。对这一模型的直接实验证实将有助于解释所有动物的性别二型性起源。

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.