Echave Julian, Wilke Claus O
Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, 1650 San Martín, Buenos Aires, Argentina; email:
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
Annu Rev Biophys. 2017 May 22;46:85-103. doi: 10.1146/annurev-biophys-070816-033819. Epub 2017 Mar 15.
For decades, rates of protein evolution have been interpreted in terms of the vague concept of functional importance. Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stronger selection pressure. More recently, biophysical models of protein evolution, which combine evolutionary theory with protein biophysics, have completely revolutionized our view of the forces that shape sequence divergence. Slowly evolving proteins have been found to evolve slowly because of selection against toxic misfolding and misinteractions, linking their rate of evolution primarily to their abundance. Similarly, most slowly evolving sites in proteins are not directly involved in function, but mutating these sites has a large impact on protein structure and stability. In this article, we review the studies in the emerging field of biophysical protein evolution that have shaped our current understanding of sequence divergence patterns. We also propose future research directions to develop this nascent field.
几十年来，蛋白质进化速率一直是根据功能重要性这一模糊概念来解释的。进化缓慢的蛋白质或蛋白质内部的位点被认为具有更重要的功能，因此受到更强的选择压力。最近，将进化理论与蛋白质生物物理学相结合的蛋白质进化生物物理模型，彻底改变了我们对影响序列差异的各种力量的看法。人们发现，进化缓慢的蛋白质之所以进化缓慢，是因为对有毒的错误折叠和错误相互作用进行了选择，这将它们的进化速率主要与它们的丰度联系起来。同样，蛋白质中大多数进化缓慢的位点并不直接参与功能，但突变这些位点会对蛋白质结构和稳定性产生很大影响。在本文中，我们回顾了生物物理蛋白质进化这一新兴领域的研究，这些研究塑造了我们目前对序列差异模式的理解。我们还提出了未来的研究方向，以发展这个新兴领域。
