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

在任何生物体中，不同的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里几乎保持不变，而另一些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的进化速度与其结构和功能角色有关，但目前尚不清楚这些因素中哪些对进化速度有独立的影响，以及每个因素的相对重要性是什么。本项目将研究进化速率变化的原因，以及潜在的分子机制。该项目将为本科生和研究生提供培训机会，项目团队将开展一些涉及高中生和公众的外展活动。历史上代表性不足的少数民族成员将成为积极的目标。普遍的观点是，蛋白质的进化速率主要由基因表达水平决定，高表达的蛋白质通常进化较慢，这种趋势被称为表达率（E-R）反相关。然而，这种反相关性的原因尚不清楚。本研究将使用实验和计算相结合的方法来测试不同的预测提出的假设来解释E-R反相关。此外，还将测试其他未确定因素对蛋白质进化速率的影响。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。

In any organism different proteins 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 slower -- 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.