生物进化是否可逆一直是人们感兴趣的问题。最新一期英国《自然》杂志刊登的研究报告说，分子水平的实验显示，蛋白质一旦向前进化，便难以原路返回过去的状态。
美国俄勒冈大学等机构的研究人员发表报告说，他们研究了一种被称为“糖皮质激素受体”的蛋白质进化路线。它存在于人和许多动物体内，具有调控精神压力等作用。研究人员重建了这种蛋白质的两个“祖先”，分别命名为AncGR1蛋白质和AncGR2蛋白质。前者可与3种激素发生反应，但经过进化、产生各种变异成为后者时，就只能与其中1种激素发生反应。
研究人员确定了与激素反应功能改变有关的7处变异，但是如果人工改造AncGR2蛋白质的结构，把这7处变异都改回去，那么这种蛋白质会失去与任何一种激素发生反应的功能。
分析显示，这是因为AncGR2蛋白质的其他一些变异不能适应其过去的蛋白质结构。虽然这些变异与激素反应功能关系不大，但它们成为逆向进化的结构障碍。换句话说，在蛋白质进化的道路上，一些变异会对另一些变异“过河拆桥”，使得后者不可能原路返回到过去状态。
这一结果表明，生物进化时体内大量的蛋白质变异会互相影响并“锁死”，使得整个进化过程难以逆转。但也有研究人员认为，可能有一些蛋白质变异在条件合适时可“绕路”回到原有状态，恢复部分进化前的功能。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 461, 515-519 (24 September 2009) | doi:10.1038/nature08249
An epistatic ratchet constrains the direction of glucocorticoid receptor evolution
Jamie T. Bridgham1, Eric A. Ortlund3 & Joseph W. Thornton1,2
1 Center for Ecology and Evolutionary Biology, and,
2 Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon 97403, USA
3 Biochemistry Department, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Correspondence to: Joseph W. Thornton1,2 Correspondence and requests for materials should be addressed to J.W.T..
The extent to which evolution is reversible has long fascinated biologists1, 2, 3, 4, 5, 6, 7, 8. Most previous work on the reversibility of morphological and life-history evolution9, 10, 11, 12, 13 has been indecisive, because of uncertainty and bias in the methods used to infer ancestral states for such characters14, 15. Further, despite theoretical work on the factors that could contribute to irreversibility1, 8, 16, there is little empirical evidence on its causes, because sufficient understanding of the mechanistic basis for the evolution of new or ancestral phenotypes is seldom available3, 8, 17. By studying the reversibility of evolutionary changes in protein structure and function, these limitations can be overcome. Here we show, using the evolution of hormone specificity in the vertebrate glucocorticoid receptor as a case-study, that the evolutionary path by which this protein acquired its new function soon became inaccessible to reverse exploration. Using ancestral gene reconstruction, protein engineering and X-ray crystallography, we demonstrate that five subsequent 'restrictive' mutations, which optimized the new specificity of the glucocorticoid receptor, also destabilized elements of the protein structure that were required to support the ancestral conformation. Unless these ratchet-like epistatic substitutions are restored to their ancestral states, reversing the key function-switching mutations yields a non-functional protein. Reversing the restrictive substitutions first, however, does nothing to enhance the ancestral function. Our findings indicate that even if selection for the ancestral function were imposed, direct reversal would be extremely unlikely, suggesting an important role for historical contingency in protein evolution.
