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

发展环境可以对一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、大多数海龟和所有鳄鱼，在特定孵化期发生的环境温度将决定个体是发育成雄性还是雌性。以前的发现揭示了内分泌系统和表观遗传学在决定环境如何影响特征方面的关键作用，即基因功能的可遗传变化而不是DNA序列的变化。该项目将确定环境和激素信号作用于表观遗传过程以形成发育轨迹和产生表型多样性的机制。该项目的重点是显示依赖温度的性别决定的物种，以解决温度如何诱导和协调根本不同的表型轨迹。这项研究将支持对两名研究生和两名本科生的培训和指导，并针对科学界代表性不足的群体进行招聘工作。该项目将开发一种初级读物，专注于传达对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。这项工作将使用最先进的测序方法来推进基于发育和内分泌的理解，以了解自然界中适应性表观遗传反应是如何发生的，以及表观遗传反应是如何被缺乏共同进化历史的环境应激源破坏的。帕罗特实验室此前曾观察到性腺基因组中广泛存在的性二态DNA甲基化模式。然而，双潜力基因组获得性二型表观基因组的发育和分子过程尚不清楚。环境敏感性的发育窗口将首先通过解析DNA甲基组在温度相关的性别决定和生殖发育期间的时间动态来确定。温度和激素的组合处理将揭示温度和内分泌信号对表观基因组重叠或不同区域的作用程度。最后，该项目将调查环境质量对性二态甲基组的影响。鉴于温度决定性别的内在环境敏感性，假设环境变量(温度以外)也影响这一过程，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。这项工作的发现将在同行评议的出版物、国家和国际科学报告中传播，并更广泛地通过与地区学校合作的外联活动传播。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。

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.