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

基因编码着地球上非同寻常的生命多样性，但在某些情况下，一种叫做朊病毒的蛋白质也可以跨代复制。它们引起各种疾病，如疯牛病和慢性消耗性疾病，但有时也提供有益的特性。这表明一些朊病毒已经被它们的宿主驯服，甚至提供了价值。与基因相比，我们对进化如何作用于朊病毒知之甚少。这一提议将是对自然选择如何作用于朊病毒的首次直接研究。此外，这项工作将提供全球酵母种群中朊病毒变异分布的特征。该项目通过增进对一类重要的新兴疾病病原体朊病毒的了解，提供了广泛的社会影响。这些信息也将有助于更好地理解病毒的进化。通过对众多本科生和研究生科学家的培训，以及通过对更广泛公众的教育和推广活动，进一步产生更广泛的影响。这一建议利用了朊病毒可以在细胞内和无细胞环境中传播的事实。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。这项拟议的研究将为从分子尺度到生物群落的进化如何影响朊病毒蛋白的起源和维持提供新的见解。该项目将重点研究一种被称为[GAR+]的朊病毒及其在酵母宿主存在和不存在的情况下的进化。预期结果包括对影响朊病毒进化的多重选择压力的有力表征，包括对宿主内或无细胞环境中进化的朊病毒的生物学效应进行全面比较。为了实现这一目标，该研究将采用在酵母和无细胞化学环境中复制朊病毒进化的实验，并将比较这两种环境之间的变化。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知识价值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.