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

任何生物体中的不同蛋白质以非常不同的速度进化;某些蛋白质的氨基酸序列在数亿年内几乎保持不变，而其他蛋白质在很短的时间内发生了巨大的变化。蛋白质序列的这些不同进化速率与它们的结构和功能作用有关，但目前尚不清楚这些因素中哪些对进化速率有独立影响，以及每个因素的相对重要性。本计画将探讨演化速率变异的原因，以及其分子机制。该项目将为本科生和研究生提供培训机会，项目小组将开展一些涉及高中生和公众的外联活动。普遍的观点是，蛋白质进化的速度主要由基因表达水平决定，高表达的蛋白质通常进化缓慢，这种趋势被称为表达率（E-R）关系。然而，这种关系的原因仍然不清楚。本研究将使用实验和计算相结合的方法来测试所提出的解释E-R关系的假设的不同预测。此外，其他未确定的因素对蛋白质进化速率的影响也将被测试。该奖项反映了NSF的法定使命，并被认为是值得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的支持。

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.