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的生命，但在某些情况下，称为朊病毒的蛋白质也可以跨代复制。它们会引起各种疾病，如疯牛病和慢性消耗病，但有时也会提供有益的性状。这表明一些朊病毒已经被它们的宿主驯服，甚至提供了一个价值。与基因相反，我们对进化如何作用于朊病毒知之甚少。这项提议将是第一次直接研究自然选择如何作用于朊病毒。此外，这项工作将提供朊病毒变体在全球酵母菌群中分布的特征。该项目通过增加对朊病毒的了解产生广泛的社会影响，朊病毒是一类重要的新兴疾病病原体。这些信息也将有助于更好地了解病毒的进化。通过培训众多本科生和研究生科学家，并通过对广大公众的教育和外联活动，产生了更广泛的影响。这个提议利用了朊病毒可以在细胞内和无细胞环境中繁殖的事实。比较每种情况下的进化结果将有助于研究朊病毒是如何被细胞驯服的。拟议的研究将导致对进化如何影响朊病毒蛋白质的起源和维持的新见解，从分子尺度到生物群落。该项目将重点关注一种名为[GAR+]的朊病毒及其在酵母宿主和非酵母宿主下的进化。预期的成果包括一个强大的多个选择压力，影响朊病毒的演变，包括一个全面的比较朊病毒的生物学效应内的主机或在无细胞环境中演变的特点。为了实现这一目标，该研究将采用复制的实验进化朊病毒在酵母和细胞的化学环境中，并将比较这两种环境之间的变化。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.