Collaborative Research: Expanding the list of determinants of rates of protein evolution and dissecting their molecular bases

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Different proteins in any organism evolve at very different speeds; the amino acid sequences of certain proteins remain virtually unaltered during hundreds of millions of years, whereas other proteins change dramatically in very short time periods. These different rates of evolution of protein sequences are connected to their structures and functional roles, but it remains unclear which of these factors have an independent effect on rates of evolution and what is the relative importance of each factor. This project will investigate the reasons of evolutionary rate variation, and the underlying molecular mechanism. The project will provide training opportunities for undergraduate and graduate students, and the project team will conduct a number of outreach activities involving high school students and the general public. Members of historically underrepresented minorities will be actively targeted.The prevailing view is that rates of protein evolution are primarily determined by gene expression levels, with highly expressed proteins usually evolving slowly -- a trend known as the expression-rate (E-R) anticorrelation. However, the reasons for this anticorrelation remain unclear. This research will use a combination of experimental and computational methods to test different predictions of the hypotheses proposed to explain the E-R anticorrelation. In addition, the impact of other, unestablished factors on rates of protein evolution will be tested.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.