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

在整个动物界，色素沉着模式在新奇和波动的环境中会发生变化。东非五大湖的慈鱼之间的颜色变化是推动它们物种形成的一个标志，这是有记录以来脊椎动物中最大的适应性辐射之一。该项目将探索DNA甲基化这一“分子开关”如何改变适应坦噶尼喀湖藻华的变色慈鱼色素细胞中基因的功能。对这些可逆的颜色变化过程的研究将提高对静态基因组和动物适应不断变化的环境的需要之间存在的流动性的理解。首席研究员(PI)将在一个研究所进行这项研究，该研究所主要服务于世界上最大、种族最多元化的城市地区本科生和研究生一级的科学方面未被充分代表的少数群体。除了在他的实验室接受培训外，动物保护协会还将在智利圣地亚哥举行的为期两周的研讨会上分享环境与基因相互作用与贫困青年的相关性，在研讨会上，动物保护协会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塑料分子机制。动物色素沉着是整个动物界的一个显著特征，使个人变得隐晦、捕食或具有性吸引力。该项目将使用具有强大和可逆颜色变体的非洲罗非鱼，以了解DNA甲基化在色素细胞在色素沉着变化过程中所起的作用。这位PI以前的工作表明，这些形态伴随着内皮素受体B启动子DNA甲基化的变化，该项目将在该领域扩大这一作用，跨越基因组，并通过其上游信号级联。利用卫星成像、湖泊形态的现场测量、高通量测序、药理学和细胞分类的组合，该项目将描述和剖析这种在整个动物界普遍存在的生态相关特征。这项提议的优势在于它将实地的环境措施进行跨学科的整合，以揭示对视觉生态学的全面理解，并在实验室进行实验验证。该项目还将把整个动物中携带色素的细胞的功能分解成与所讨论的特征直接对应的丰富的细胞群体，从而消除通常限制这些研究解释的细胞异质性的障碍。预计这项研究的结果将与进化论、视觉生态学和细胞生物学领域广泛相关。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.