CAREER: Discovery of the molecular mechanisms underlying microevolution of phenotypic plasticity in a developmental trait

职业：发现发育性状表型可塑性微进化的分子机制

• 批准号: 1751035
• 负责人: Erik Andersen
• 金额: $ 53.08万
• 依托单位: Northwestern University
• 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: 2018-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1751035&HistoricalAwards=false
• 关键词: CAREER; Discovery; molecular; mechanisms; underlying

When organisms are exposed to environmental differences, like changes in temperature conditions, they can grow into alternative forms that are more adapted to particular environments. This project investigates how a nematode roundworm makes the decision to become a long-lived and stress-resistant form instead of a proliferative form that is stress-sensitive. Currently there is little understanding how these types of decisions are made at the molecular level. High-throughput measurements, genome sequencing, and genetic methods will be used to examine this mystery and lay the groundwork for future projects examining how animal development changes in responses to divergent environmental cues. Undergraduate and high school student training is an important component of this grant. High school teachers will develop classroom activities for STEM students in cooperation with the principal investigator and high school students will visit the laboratory to carry out hands on experiments with the worms.Phenotypic plasticity, or the expression of different phenotypes by the same genotype, drives evolutionary adaptation to shifting environments. Despite numerous well-known examples, little is known about the genetic underpinnings and molecular mechanisms that generate phenotypic plasticity. The goal of this grant is to discover how microevolution of this plasticity occurs using the tractable metazoan system Caenorhabditis elegans. Depending on environmental conditions, these nematodes enter an alternative developmental fate, called dauer, or continue development to reproductive adults. Early larval-stage animals that sense high temperature, low food availability, and high population density initiate the development of the dauer stage. Once conditions improve, dauers re-enter development to become reproductive adults. Much of what is known about dauer comes from the study of a single laboratory strain. Although natural variation in dauer formation has been observed, the molecular mechanisms that lead to phenotypic differences remain unknown. An unbiased approach is needed to discover the genes that underlie natural variation in dauer formation in order to understand how phenotypic plasticity evolves. Species-wide association mapping will be performed using a novel high-throughput assay in order to identify loci that underlie differences in this developmental trait. These loci will be narrowed to candidate genes using well tested experimental and computational techniques and then variants will be validated using genome editing. These approaches will lead to discovery of the number and the sizes of genetic effects, the signatures of selection that occur at those loci, and then define the parts of the dauer network involved in the microevolution of phenotypic plasticity.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.

当生物体暴露于环境差异时，如温度条件的变化，它们可以生长成更适应特定环境的替代形式。该项目研究线虫如何决定成为一种长寿和抗应激的形式，而不是对应激敏感的增殖形式。目前，人们对这些类型的决定是如何在分子水平上做出的还知之甚少。高通量测量、基因组测序和遗传学方法将用于研究这一谜团，并为未来研究动物发育如何响应不同环境线索的项目奠定基础。 本科生和高中生培训是这项赠款的一个重要组成部分。 高中教师将与首席研究员合作为STEM学生开发课堂活动，高中学生将参观实验室，用蠕虫进行动手实验。表型可塑性，或同一基因型表达不同表型，推动进化适应不断变化的环境。尽管有许多众所周知的例子，但人们对产生表型可塑性的遗传基础和分子机制知之甚少。这项资助的目的是发现这种可塑性的微进化是如何使用易处理的后生动物系统秀丽隐杆线虫发生的。根据环境条件，这些线虫进入另一种发育命运，称为dauer，或继续发育为生殖成虫。早期幼虫阶段的动物，感觉高温，低食物供应，和高人口密度启动发展的dauer阶段。一旦条件改善，幼鸟重新进入发育阶段，成为有生殖能力的成年鸟。人们对道尔的了解大多来自于对一种实验室菌株的研究。虽然已经观察到dauer形成的自然变异，但导致表型差异的分子机制仍然未知。为了了解表型可塑性如何演变，需要一种无偏见的方法来发现dauer形成中自然变异的基础基因。物种范围内的关联映射将使用一种新的高通量测定，以确定基因座的基础上，在这个发展性状的差异。这些基因座将使用经过充分测试的实验和计算技术缩小到候选基因，然后使用基因组编辑验证变体。这些方法将导致发现遗传效应的数量和大小、发生在这些基因座的选择特征，然后定义参与表型可塑性微观进化的道尔网络部分。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智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Why worms matter: the importance of nematode diversity for studying biology and evolution

为什么蠕虫很重要：线虫多样性对于研究生物学和进化的重要性

• DOI: 10.33424/futurum201
• 发表时间: 2021
• 期刊: Futurum Careers
• 作者: Andersen, Erik

A Highly Scalable Approach to Perform Ecological Surveys of Selfing Caenorhabditis Nematodes

一种高度可扩展的方法对自交线虫进行生态调查

• DOI: 10.3791/63486
• 发表时间: 2022
• 期刊: Journal of Visualized Experiments
• 作者: Crombie, Timothy A.;Tanny, Robyn E.;Buchanan, Claire M.;Roberto, Nicole M.;Andersen, Erik C.
• 通讯作者: Andersen, Erik C.