EAGER: Functional genomics of genes under selection in natural populations

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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.