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

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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.