Collaborative Research: From Molecules to Communities: How Levels of Selection Integrate to Tame Selfish Elements

基因编码了地球上异常多样化的生命，但在某些情况下，被称为Pron的蛋白质也可以在几代人之间复制。它们会导致各种疾病，如疯牛病和慢性消耗性疾病，但有时也会提供有益的特征。这表明一些普恩病毒已经被它们的宿主驯服了，甚至提供了价值。与基因不同的是，我们对进化如何作用于普恩病毒知之甚少。这项提议将是关于自然选择如何作用于普恩的第一次直接调查。此外，这项工作将提供全球酵母种群中普恩变异体分布的特征。该项目通过增加对作为一类新出现的疾病病原体的重要类别的普恩的了解，提供广泛的社会影响。这些信息还将使人们更好地了解病毒的进化。通过培训许多本科生和研究生科学家，以及通过面向更广泛公众的教育和外联活动，产生了更广泛的影响。这一提议利用了这样一个事实，即普恩可以在细胞内和无细胞环境中传播。通过比较每种情况下的进化结果，可以研究细胞是如何驯服普恩病毒的。这项拟议的研究将导致对进化如何影响从分子水平到生物群落的普恩蛋白的起源和维持的新见解。该项目将专注于一种名为[GAR+]的Prion及其在酵母宿主存在和不存在的情况下的进化。预期的结果包括对影响普恩进化的多种选择压力进行强有力的描述，包括对在宿主或无细胞环境中进化的普恩的生物效应进行全面比较。为了实现这一目标，这项研究将采用在酵母和无细胞化学环境中复制普恩的实验进化，并将比较这两种环境之间的变化。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。

Genes code for an extraordinary diversity of life on earth but in some circumstances, proteins called prions can also replicate across generations. They cause various diseases such as mad cow disease and chronic wasting disease but also sometimes provide beneficial traits. This suggests that some prions have been tamed by their hosts, and even provide a value. In contrast to genes, we understand very little about how evolution acts on prions. This proposal will be the first direct investigation of how natural selection acts on prions. In addition, the work will provide a characterization of the distribution of prion variants in the global yeast population. The project provides broad societal impact through increased understanding of prions which are an important class of emerging disease agents. This information will also allow a better understanding of viral evolution. Further broader impacts arise through the training of numerous undergraduate and graduate scientists, and through educational and outreach activities to the broader public. This proposal takes advantage of the fact that prions can be propagated both inside of cells and in a cell-free environment. Comparing the outcomes of evolution in each of these conditions will allow an examination of how prions are tamed by cells. The proposed research will lead to new insights into how evolution has impacted the origin and maintenance of prion proteins, spanning from the molecular scale to biological communities. The project will focus on one prion, termed [GAR+] and its evolution with and without a yeast host. Expected outcomes include a robust characterization of the multiple selective pressures that influence prion evolution including a comprehensive comparisons of the biological effects of prions evolved within a host or in a cell-free environment. To achieve this the study will employ a replicated experimental evolution of prions in yeast and in cell free chemical environments and will compare the changes between these two environments.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.