Inventing monogamy: innovation and adaptation in the epigenome

发明一夫一妻制：表观基因组的创新和适应

• 批准号: 1457350
• 负责人: Steven Phelps
• 金额: $ 68.69万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1457350&HistoricalAwards=false
• 关键词: Inventing; monogamy; innovation; adaptation; epigenome

How do new behaviors evolve? Recent technical advances allow us to ask exactly which deoxyribonucleic acid (DNA) sequences underlie evolutionary innovations in gene expression, neural function, and complex behaviors. The ability of an organism to form a bond with another individual is a complex behavior, one that shapes the social behaviors exhibited by many species, including humans. In the current project, the investigators identify evolutionary adaptations that underlie social bonding in a well-studied species, the monogamous prairie vole. The investigators compare the subtle changes in DNA sequences that distinguish monogamous prairie voles from promiscuous relatives. They also ask whether these changes in DNA influence gene function in brain regions important for pair-bonding as well as brain regions important for spatial memory because space use is a major factor in animal mating systems. Lastly, the investigators ask whether natural selection has operated on these DNA sequences by examining patterns of DNA variation. The findings will help understand how changes in complex behavior can emerge from variation in DNA. To complete the studies, the investigators will recruit and train undergraduates from under-represented groups. Further, the investigators will develop and disseminate research tools needed to perform similar studies on a great variety of species, making it easier to do cutting-edge studies of genome function and behavior in any species. The answers obtained from this work will elucidate the relation between behavior and subtle genetic variations that contribute to diversity and disease.How is an existing genotype sculpted, locus by locus, to result in a new phenotype? The investigators use the genus Microtus as a model for understanding the epigenetic innovations that gave rise to social monogamy, building on an extensive body of work in social neuroscience, molecular genetics, and behavioral ecology. They examine the epigenome and its evolution in three vole species: the monogamous prairie vole, M. ochrogaster; the promiscuous meadow vole, M. pennsylvanicus; and a promiscuous outgroup, the California vole, M. californicus. Although many brain regions merit study, the investigators focus on four brain regions: reward structures (nucleus accumbens, ventral pallidum) and spatial memory structures (hippocampus, retrosplenial cortex). In the first aim, they use RNA-seq and ChIP-seq to identify species differences in gene regulation. In second aim, they use phylogenetic and population genetic methods to identify adaptations within the epigenome. The intersection of these two data sets will identify regulatory regions likely to be causally involved in pair-bond formation, and in mating system differences in spatial cognition. Finally, the investigators test whether the evolution of monogamy in this group relied predominantly on changes related to bonding, to cognition, or both. The identified DNA sequences can then be subject to manipulation in future studies.

新行为是如何进化的？最近的技术进步使我们能够确切地了解哪些脱氧核糖核酸（DNA）序列是基因表达、神经功能和复杂行为的进化创新的基础。一个生物体与另一个个体形成联系的能力是一种复杂的行为，它塑造了包括人类在内的许多物种所表现出的社会行为。在目前的项目中，研究人员确定了一个被充分研究的物种--一夫一妻制草原田鼠--的进化适应性，这些适应性是社会联系的基础。研究人员比较了DNA序列的细微变化，这些变化将一夫一妻制的草原田鼠与滥交的亲戚区分开来。他们还询问DNA的这些变化是否影响了对配对重要的大脑区域以及对空间记忆重要的大脑区域的基因功能，因为空间使用是动物交配系统的主要因素。最后，研究人员通过检查DNA变异的模式来询问自然选择是否对这些DNA序列起作用。这些发现将有助于理解复杂行为的变化如何从DNA的变化中出现。为了完成这项研究，研究人员将从代表性不足的群体中招募和培训本科生。此外，研究人员将开发和传播对各种物种进行类似研究所需的研究工具，使其更容易在任何物种中进行基因组功能和行为的前沿研究。从这项工作中获得的答案将阐明行为与导致多样性和疾病的微妙遗传变异之间的关系。一个现有的基因型是如何一个位点一个位点地塑造出来，从而产生一个新的表型的？研究人员使用田鼠属作为模型来理解引起社会一夫一妻制的表观遗传创新，建立在社会神经科学，分子遗传学和行为生态学的广泛工作基础上。他们研究了三种田鼠的表观基因组及其进化：一夫一妻制的草原田鼠，M。ochrogaster;滥交草地田鼠M. pennaculicus和一个混杂的外群，加州田鼠，M.加利福尼亚州。虽然许多大脑区域值得研究，但研究人员集中在四个大脑区域：奖励结构（丘脑核，腹侧苍白球）和空间记忆结构（海马，压后皮质）。在第一个目标中，他们使用RNA-seq和ChIP-seq来识别基因调控的物种差异。在第二个目标中，他们使用系统发育和群体遗传学方法来识别表观基因组中的适应性。这两个数据集的交集将确定可能是因果关系参与配对键的形成，并在交配系统的空间认知差异的监管区域。最后，研究人员测试了这一群体中一夫一妻制的演变是否主要依赖于与结合、认知或两者相关的变化。然后可以在未来的研究中对鉴定出的DNA序列进行操作。