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Adaptive and disruptive epigenome-by-environment dynamics: molecular mechanisms to ecological impacts

环境动态的适应性和破坏性表观基因组：生态影响的分子机制

基本信息

批准号：
1754903
负责人：
Benjamin Parrott
金额：
$ 57.18万
依托单位：
University of Georgia Research Foundation Inc
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1754903&HistoricalAwards=false
关键词：
Adaptive disruptive epigenome environment dynamics

项目摘要

The developmental environment can have profound impacts on an individual. For example, in many non-mammalian vertebrates including some fish, most turtles, and all crocodilians, environmental temperatures occurring during a specific period of incubation will determine if individuals develop as either a male or female. Previous findings have revealed a critical role for the endocrine system and epigenetics, heritable changes in gene function without changes in DNA sequence, in determining how the environment impacts traits. This project will determine the mechanisms by which environments and hormone signaling act on epigenetic processes to shape developmental trajectories and produce phenotypic diversity. The project focuses on species displaying temperature-dependent sex determination, to address how temperature induces and coordinates radically different phenotypic trajectories. The study will support the training and mentoring of two graduate students and two undergraduate researchers, with recruiting efforts aimed at under-represented groups in the sciences. The project will develop a primer focused on communicating common misperceptions about epigenetics. The findings will be presented to students at area schools as part of an established outreach program. Together, this work will advance the understanding of the mechanisms that determine how organisms interact with the environments and will provide training opportunities for the next generation of scientists. The work will employ state of the art sequencing approaches to advance a developmental- and endocrine-based understanding of how adaptive epigenetic responses occur in nature, and how epigenetic responses are disrupted by environmental stressors for which a shared evolutionary history is absent. The Parrott Lab has previously observed widespread sexually dimorphic DNA methylation patterning across the gonadal genome. However, the developmental and molecular processes by which a bipotential genome acquires a sexually dimorphic epigenome is unclear. Developmental windows of environmental sensitivity will first be identified by resolving the temporal dynamics of the DNA methylome during temperature-dependent sex determination and reproductive development. Combinatorial treatments of temperature and hormones will then reveal the degree to which temperature and endocrine signals act on overlapping or distinct regions of the epigenome. Finally, the project will investigate the influence of environmental quality on the sexually dimorphic methylome. Given the inherent environmental sensitivity of temperature-dependent sex determination, it is hypothesized that environmental variables (other than temperature) also influence this process to affect the development and subsequent function of the reproductive system. Together, experiments will reveal how environmental and biological signals are integrated into developmental processes that result in phenotypic diversity. Findings from this work will be disseminated in peer-reviewed publications, presentations at national and international scientific, and more broadly via outreach activities in partnership with area schools.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.

发展环境会对个人产生深远的影响。例如，在许多非哺乳类脊椎动物中，包括一些鱼类，大多数海龟和所有鳄鱼，在特定的孵化期内发生的环境温度将决定个体是否发育为雄性或雌性。以前的研究结果揭示了内分泌系统和表观遗传学的关键作用，即基因功能的遗传变化而不改变DNA序列，在确定环境如何影响性状方面。这个项目将确定环境和激素信号作用于表观遗传过程的机制，以塑造发育轨迹并产生表型多样性。该项目的重点是显示温度依赖性性别决定的物种，以解决温度如何诱导和协调根本不同的表型轨迹。该研究将支持两名研究生和两名本科生研究人员的培训和指导，并针对科学领域代表性不足的群体进行招聘。该项目将开发一个初级读本，重点是交流关于表观遗传学的常见误解。调查结果将作为既定推广计划的一部分提交给地区学校的学生。总之，这项工作将促进对决定生物体如何与环境相互作用的机制的理解，并将为下一代科学家提供培训机会。这项工作将采用最先进的测序方法，以推进基于发育和内分泌的理解，了解适应性表观遗传反应如何在自然界中发生，以及表观遗传反应如何被缺乏共同进化历史的环境压力源破坏。帕罗特实验室先前已经观察到在整个性腺基因组中广泛存在的性二态DNA甲基化模式。然而，发育和分子过程中，一个双能基因组获得性二态表观基因组是不清楚的。环境敏感性的发育窗口将首先通过解决温度依赖性性别决定和生殖发育过程中DNA甲基化的时间动态来确定。温度和激素的组合治疗将揭示温度和内分泌信号作用于表观基因组重叠或不同区域的程度。最后，该项目将调查环境质量对性二态甲基化组的影响。鉴于温度依赖性性别决定的固有环境敏感性，假设环境变量（温度以外）也会影响这一过程，从而影响生殖系统的发育和随后的功能。总之，实验将揭示环境和生物信号如何整合到导致表型多样性的发育过程中。这项工作的结果将通过同行评审的出版物、国家和国际科学会议上的演讲以及与地区学校合作开展的更广泛的外联活动进行传播。该奖项反映了NSF的法定使命，并被认为值得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来支持。