生物進化是否可逆一直是人們感興趣的問題,。最新一期英國《自然》雜志刊登的研究報告說,，分子水平的實驗顯示,，蛋白質一旦向前進化,，便難以原路返回過去的狀態(tài)。
美國俄勒岡大學等機構的研究人員發(fā)表報告說,，他們研究了一種被稱為“糖皮質激素受體”的蛋白質進化路線,。它存在于人和許多動物體內(nèi)，具有調(diào)控精神壓力等作用,。研究人員重建了這種蛋白質的兩個“祖先”,，分別命名為AncGR1蛋白質和AncGR2蛋白質。前者可與3種激素發(fā)生反應,，但經(jīng)過進化,、產(chǎn)生各種變異成為后者時，就只能與其中1種激素發(fā)生反應,。
研究人員確定了與激素反應功能改變有關的7處變異,，但是如果人工改造AncGR2蛋白質的結構，把這7處變異都改回去,，那么這種蛋白質會失去與任何一種激素發(fā)生反應的功能,。
分析顯示，這是因為AncGR2蛋白質的其他一些變異不能適應其過去的蛋白質結構,。雖然這些變異與激素反應功能關系不大,，但它們成為逆向進化的結構障礙。換句話說,，在蛋白質進化的道路上,，一些變異會對另一些變異“過河拆橋”，使得后者不可能原路返回到過去狀態(tài),。
這一結果表明,，生物進化時體內(nèi)大量的蛋白質變異會互相影響并“鎖死”，使得整個進化過程難以逆轉,。但也有研究人員認為,，可能有一些蛋白質變異在條件合適時可“繞路”回到原有狀態(tài)，恢復部分進化前的功能,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
