Ronneberg T A, Landweber L F, Freeland S J
Departments of Ecology and Evolutionary Biology, and Chemistry, Princeton University, Princeton, NJ 08544, USA.
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13690-5. doi: 10.1073/pnas.250403097.
It has long been conjectured that the canonical genetic code evolved from a simpler primordial form that encoded fewer amino acids [e.g., Crick, F. H. C. (1968) J. Mol. Biol. 38, 367-379]. The most influential form of this idea, "code coevolution" [Wong, J. T.-F. (1975) Proc. Natl. Acad. Sci. USA 72, 1909-1912], proposes that the genetic code coevolved with the invention of biosynthetic pathways for new amino acids. It further proposes that a comparison of modern codon assignments with the conserved metabolic pathways of amino acid biosynthesis can inform us about this history of code expansion. Here we re-examine the biochemical basis of this theory to test the validity of its statistical support. We show that the theory's definition of "precursor-product" amino acid pairs is unjustified biochemically because it requires the energetically unfavorable reversal of steps in extant metabolic pathways to achieve desired relationships. In addition, the theory neglects important biochemical constraints when calculating the probability that chance could assign precursor-product amino acids to contiguous codons. A conservative correction for these errors reveals a surprisingly high 23% probability that apparent patterns within the code are caused purely by chance. Finally, even this figure rests on post hoc assumptions about primordial codon assignments, without which the probability rises to 62% that chance alone could explain the precursor-product pairings found within the code. Thus we conclude that coevolution theory cannot adequately explain the structure of the genetic code.
长期以来，人们一直推测标准遗传密码是从一种编码较少氨基酸的更简单的原始形式进化而来的[例如，克里克，F.H.C.（1968年）《分子生物学杂志》38卷，367 - 379页]。这个观点最有影响力的形式，即“密码子共同进化”[王，J.T.-F.（1975年）《美国国家科学院院刊》72卷，1909 - 1912页]，提出遗传密码是与新氨基酸生物合成途径的发明共同进化的。它还提出，将现代密码子分配与氨基酸生物合成的保守代谢途径进行比较，可以让我们了解密码扩展的历史。在这里，我们重新审视这一理论的生化基础，以检验其统计支持的有效性。我们表明，该理论对“前体 - 产物”氨基酸对的定义在生化上是不合理的，因为它需要现存代谢途径中步骤的能量上不利的逆转才能实现所需的关系。此外，该理论在计算偶然将前体 - 产物氨基酸分配到相邻密码子的概率时忽略了重要的生化限制。对这些错误进行保守修正后发现，密码内明显模式纯粹由偶然导致的概率高得出奇，为23%。最后，即使这个数字也基于关于原始密码子分配的事后假设，没有这些假设，仅靠偶然就能解释密码内发现的前体 - 产物配对的概率升至62%。因此，我们得出结论，共同进化理论不能充分解释遗传密码的结构。
