Connecting genes and social behavior in a unique animal model

由于在基因组学和行为学方面普遍缺乏跨学科的专业知识，社会行为的遗传基础研究进展缓慢。这个项目是一名接受过分子生物学和遗传学培训的PI和一名接受过社会行为及其荷尔蒙机制分析的联合PI之间的合作。新的高通量测序方法能够在各种精心选择的物种中详细研究社会行为的遗传基础，即使在没有完全测序的基因组的情况下也是如此。一种名为白喉麻雀的鸣鸟模型被用来描述参与攻击的基因。本种表现出与社会行为的许多方面相关的羽毛多态。皇冠上有白色条纹(WS)的人比棕色条纹(TS)的人更具攻击性，唱歌的几率也更高。这种羽毛多态与染色体重排有关，为研究基因和社会行为之间的关系提供了一个独特的机会。该项目使用功能强大且令人兴奋的下一代测序技术来识别大脑中与羽毛形态和攻击行为相关的表达变化的基因。一旦确定，这些基因的表达就会在大脑中得到映射，以帮助澄清它们在行为中的作用。对基因序列进行分析，以确定与羽毛形态有关的蛋白质序列的变异。这些结果为攻击性相关基因的表达、序列和分布提供了广泛的信息。智力价值：全基因组关联研究已经确定了大量单核苷酸多态，这些多态与表型的关联很弱，但解释的变异很少。基因多态和诸如“攻击性”这样的行为结构之间的联系仍然缺乏，这主要是因为没有考虑到发生在基因转录和蛋白质功能水平上的中间步骤。这一领域的进展不仅需要了解基因序列是否有助于行为，还需要了解它们是如何影响行为的。因此，行为科学将受益于经过培训以解决这些问题的研究人员的专业知识。在这个项目中，一位具有分子生物学背景的PI加入了一个心理学系，并将基因组学技术和资源整合到社会行为研究中。旨在阐明驱动社会行为的机制的研究必须以一种允许动物在自然环境中互动的方式进行。对实验室饲养的动物进行的行为研究通常不代表自然条件，也可能产生与生物学无关的结果。这项研究利用在自然栖息地观察和收集的动物，将基因和社会行为联系起来。虽然社会行为是复杂的，预计会涉及许多基因，但只有少数基因与社会行为有明确的联系。这些结果极大地有助于我们对鸣禽大脑中基因表达的知识库，这是一个有助于研究基因和行为之间关系的重要模型。广泛影响：PI开发并教授一门课程，目标是对基于遗传学的方法感兴趣的心理学研究生，该课程强调基本的基因功能，基因组数据库的使用，以及多态和行为之间的关联的解释。最终，这门课程鼓励心理学学生将遗传学方法以一种强有力的方式整合到他们的研究中。PI的其他活动包括指导本科生，在服务不足的K-12学校做演讲，以及指导来自代表不足群体的高中生和教师。

Research on the genetic basis of social behavior has proceeded slowly because of a general lack of interdisciplinary expertise in both genomics and behavior. This project is a collaboration between a PI trained in molecular biology and genetics and a co-PI trained in the analysis of social behavior and its hormonal mechanisms. New high-throughput sequencing methods enable the detailed study of the genetic basis of social behavior in a variety of carefully chosen species, even in the absence of a completely sequenced genome. A songbird model, the white-throated sparrow, is used to characterize genes involved in aggression. This species exhibits a plumage polymorphism that correlates with many aspects of social behavior. Individuals with a white stripe (WS) on the crown are more aggressive and have higher song rates than individuals with a tan stripe (TS). The plumage polymorphism is linked to a chromosomal rearrangement, presenting a unique opportunity to study the relationship between genes and social behavior. This project uses the powerful and exciting technology of next-generation sequencing to identify genes in the brain that vary in expression with relation to both plumage morph and aggressive behavior. Once identified, the expressions of these genes are mapped in the brain to help clarify their role in behavior. Gene sequences are analyzed to identify variation in protein sequence that is linked to plumage morph. These results provide extensive information on the expression, sequence, and distribution of genes linked to aggression. Intellectual Merit:Genome-wide association studies have identified a vast array of single nucleotide polymorphisms that are weakly associated with phenotypes but which explain very little variation. The link between genetic polymorphisms and behavioral constructs such as "aggression" is still lacking, largely because of a failure to consider the intermediary steps that happen at the levels of gene transcription and protein function. Progress in this field will require an understanding not only of whether gene sequences contribute to behavior, but how they do so. The behavioral sciences would thus benefit from the expertise of researchers trained to address these questions. In this project, a PI with a background in molecular biology joins a psychology department and integrates genomics techniques and resources into the study of social behavior. It is essential that studies intended to elucidate the mechanisms driving social behavior be conducted in a way that allows animals to interact in their natural environment. Behavioral studies on laboratory-housed animals often do not represent naturalistic conditions, and can produce results that are not biologically relevant. This study links genes and social behavior using animals that are observed and collected in their natural habitat. Although social behavior is complex and predicted to involve many genes, only a few genes have been definitively linked to social behavior. These results greatly contribute to our knowledge base of gene expression in the brains songbirds, an important model useful for studying the relationship between genes and behavior.Broader Impacts:The PI develops and teaches a course, aimed at psychology graduate students interested in genetics-based approaches, which emphasizes basic gene function, the use of genomics databases, and the interpretation of associations between polymorphisms and behavior. Ultimately the course encourages psychology students to integrate genetic approaches in to their research in a powerful way. The PI's other activities include mentoring undergraduates, making presentations at underserved K-12 schools, and mentoring high school students and teachers from underrepresented groups.