Wang Zhengyuan O, Pollock David D
Department of Biological Sciences, Biological Computation and Visualization Center, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Methods Enzymol. 2005;395:779-90. doi: 10.1016/S0076-6879(05)95040-4.
As complete genomes accumulate and the generation of genomic biodiversity proceeds at an accelerating pace, the need to understand the interaction between sequence evolution and protein structure and function rises in prominence. The pattern and pace of substitutions in proteins can provide important clues to functional importance, functional divergence, and adaptive response. Coevolution between amino acid residues and the context dependence of the evolutionary process are often ignored, however, because of their complexity, but they are critical for the accurate interpretation of reconstructed evolutionary events. Because residues interact with one another, and because the effect of substitutions can depend on the structural and physiological environment in which they occur, an accurate science of evolutionary functional genomics and a complete understanding of selection in proteins require a better understanding of how context dependence affects protein evolution. Here, we present new evidence from vertebrate cytochrome oxidase sequences that pairwise coevolutionary interactions between protein residues are highly dependent on tertiary and secondary structure. We also discuss theoretical predictions that impinge on our expectations of how protein residues may interact over long distances because of their shared need to maintain protein stability.
随着完整基因组的不断积累以及基因组生物多样性的产生速度日益加快，理解序列进化与蛋白质结构和功能之间相互作用的需求愈发突出。蛋白质中替换的模式和速度能够为功能重要性、功能分化及适应性反应提供重要线索。然而，由于氨基酸残基之间的协同进化以及进化过程的背景依赖性十分复杂，常常被忽视，但它们对于准确解读重建的进化事件至关重要。由于残基之间相互作用，且替换的效应可能取决于其发生的结构和生理环境，因此，进化功能基因组学的精确科学以及对蛋白质选择的全面理解需要更好地了解背景依赖性如何影响蛋白质进化。在此，我们展示了来自脊椎动物细胞色素氧化酶序列的新证据，即蛋白质残基之间的成对协同进化相互作用高度依赖于三级和二级结构。我们还讨论了一些理论预测，这些预测影响着我们对于蛋白质残基因共同需要维持蛋白质稳定性而可能进行长距离相互作用的预期。
