EAGER: Functional genomics of genes under selection in natural populations

这个急切的项目解决了进化遗传学研究的一个长期目标--在自然选择下识别和表征基因。这样的研究可以更好地理解进化力量和对表型变化的制约以及对环境挑战的潜在反应。下一代测序和全基因组基因分型技术在进化研究中催生了一场革命。形态、行为和生理特征的遗传基础可能被揭示，并在自然种群中研究它们的进化动力学。然而，对非模式物种的研究的一个限制是，自然选择下的基因功能不容易在野外探索，因为对个人的实验操作可能是有限的。在这项研究中，研究人员提出了一种新的方法来理解被选择基因的功能，该方法涉及到从表达被选择基因的组织建立的细胞培养的研究。研究人员将在来自灰狼和黑狼多个组织的细胞中演示这种方法，在这些细胞中，一个基因的单一替换就会赋予毛色表型。该基因还在细胞免疫、对感染的抗菌反应、甚至参与生殖和攻击性行为方面发挥作用。研究人员计划开发细胞培养、转录组收集和网络分析的协议，这些协议可以普遍应用于其他动物物种。可以在这些细胞系中研究不同的基因变体，并通过基因表达网络分析来评估它们对细胞和机体功能的影响。这种方法的结果将是对功能的预测，可以通过对自然种群的研究进一步检验。该项目将为加州大学洛杉矶分校的博士后研究员和研究生提供机会，学习研究基因功能的新的分子和生物信息学方法。此外，该项目还提供了一个使用狼狗系统向公众传达进化信息的范例。该项目还将为研究人员和合作者以及对该项目感兴趣的公众和学生建立网上查阅结果的途径。

This EAGER project addresses a long-standing goal of evolutionary genetic studies - the identification and characterization of genes under natural selection. Such studies can lead to a better understanding of the evolutionary forces and constraints on phenotypic change and potential responses to environmental challenges. Next generation sequencing and genome wide genotyping technology have spawned a revolution in evolutionary studies. The genetic basis of morphological, behavioral and physiological traits can potentially be uncovered and their evolutionary dynamics studied in natural populations. However, a limitation with research on non-model species is that the function of genes under natural selection cannot easily be explored in the wild because experimental manipulations on individuals may be limited. In this study, the investigators propose a novel approach for understanding function of genes under selection that involves study of cell cultures established from tissues that express the genes under selection. The researchers will demonstrate this approach in cells derived from multiple tissues of gray and black wolves, where a single substitution in a gene confers coat color phenotypes. This gene also has roles in cellular immunity, antibacterial response to infection, and even an involvement in reproductive and aggressive behavior. The investigators plan to develop protocols for cell culture, transcriptome collection, and network analysis that can be generally applied to other animal species. Different variants of genes can be studied in these cell lines and their effect on cell and organism function assessed through a gene expression network analysis. The results of this approach will be predictions of function that can be further tested by study of natural populations. The project will provide opportunities for a postdoctoral researcher and graduate students at UCLA to learn new molecular and bioinformatic approaches to study gene function. Additionally, this project provides an example for conveying evolution information to the public using the wolf-dog system. The project will also establish web-based access to findings aimed at researchers and collaborators as well as the public and students who have interest in the project.