URoL: Epigenetics 1: Characterization and dissection of DNA methylation and animal color changes in an African cichlid

在整个动物王国中，色素沉着模式在新的和波动的环境中会发生变化。东非五大湖慈鲷的颜色变化是推动其物种形成的一个标志，这是脊椎动物中有记录的最大适应性辐射之一。这个项目将探索一种“分子开关”，DNA甲基化，如何改变一种适应坦噶尼喀湖藻华的变色鲷的色素细胞中的基因功能。对这些可逆颜色变化过程的研究将提高对静态基因组与动物适应不断变化的环境之间存在的流动性的理解。首席研究员（PI）将在一个研究所开展这项研究，该研究所主要为世界上最大的种族最多样化的城市地区的本科和研究生阶段的代表性不足的少数民族提供服务。除了在他的实验室提供培训机会外，在智利圣地亚哥举行的为期两周的讲习班上，PI将与贫困青年分享环境-基因相互作用的相关性，PI将教授影响人类健康和疾病的遗传决定因素的相关性以及随着社会经济地位、逆境和精神疾病而变化的可塑性分子机制。动物色素沉着是动物界的一个显著特征，它使个体变得神秘、掠食或具有性吸引力。该项目将使用burtoni Astatotilapia，这是一种非洲鲷鱼，具有强大和可逆的颜色变化，以加深对DNA甲基化在色素沉着变化过程中承载色素细胞功能中的作用的理解。该PI之前的工作表明，这些形态伴随着内皮素受体B启动子DNA甲基化的改变，该项目将扩大这一领域的作用，跨越基因组，并通过它们的上游信号级联。结合卫星成像、湖泊形态的原位测量、高通量测序、药理学和细胞分选，该项目将描述和剖析这种在动物王国中普遍存在的生态相关特征。该提案的优势在于它将该领域的环境措施跨学科地整合在一起，揭示了对视觉生态学的全面理解，并在实验室进行了实验验证。该项目还将解决整个动物中携带色素细胞的功能，将其转化为直接对应于所讨论的性状的富集细胞群，从而消除通常限制这些研究解释的细胞异质性障碍。预计本研究结果将广泛应用于进化、视觉生态学和细胞生物学等领域。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Across the animal kingdom, pigmentation patterns are subject to change in novel and fluctuating environments. Color variation among cichlid fish in the East African Great Lakes is a hallmark driving their speciation in one of the largest adaptive radiations recorded among vertebrates. This project will explore how a "molecular switch", DNA methylation, can change the function of genes in the pigment cells of a color-changing cichlid fish adapting to the algal blooms of Lake Tanganyika. The study of these reversible color changing processes will improve the understanding of the fluidity that exists between a static genome and an animals' need to adapt to an ever-changing environment. The principal investigator (PI) will carry out this research at an institute that primarily serves under-represented minorities in science at the undergraduate and graduate level in the largest most ethnically diverse urban area in the world. In addition to training opportunities in his laboratory, the PI will share the relevance of environment-by-gene interactions to underprivileged youths during two-week workshops held in Santiago, Chile, where the PI will teach the relevance of the genetic determinants that affect human health and disease and the plastic molecular mechanisms that change with socio-economic position, adversity, and mental illness.Animal pigmentation is a salient trait across the animal kingdom that allows an individual to become cryptic, predatory, or sexually attractive. The project will use Astatotilapia burtoni, an African cichlid fish, with robust and reversible color morphs to develop the understanding of the role DNA methylation plays in the function of pigment-bearing cells during changes in pigmentation. Previous work by this PI has shown that these morphs are accompanied by alterations in DNA methylation of the Endothelin Receptor B promoter and this project will expand this role in the field, across the genome, and through their upstream signaling cascades. Using a combination of satellite imaging, in situ measurements of lake morphology, high throughput sequencing, pharmacology, and cell sorting, the project will characterize and dissect this ecologically relevant trait that is ubiquitous throughout the animal kingdom. The strength of this proposal lies within its interdisciplinary integration of environmental measures in the field to reveal a comprehensive understanding of visual ecology with experimental validation carried out in the laboratory. The project will also resolve the function of pigment-bearing cells across an entire animal into enriched cell populations that directly correspond to the trait in question, thus eliminating hurdles of cell heterogeneity that typically limit the interpretation of these studies. It is anticipated that the findings from this study will be widely relevant to the field of evolution, visual ecology, and cellular biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.