Di Giulio Massimo
Laboratory for Molecular Evolution, Institute of Genetics and Biophysics Adriano Buzzati Traverso, CNR, Via P. Castellino, 111, 80131 Naples, Napoli, Italy.
Biol Direct. 2008 Sep 5;3:37. doi: 10.1186/1745-6150-3-37.
The coevolution theory of the origin of the genetic code suggests that the genetic code is an imprint of the biosynthetic relationships between amino acids. However, this theory does not seem to attribute a role to the biosynthetic relationships between the earliest amino acids that evolved along the pathways of energetic metabolism. As a result, the coevolution theory is unable to clearly define the very earliest phases of genetic code origin. In order to remove this difficulty, I here suggest an extension of the coevolution theory that attributes a crucial role to the first amino acids that evolved along these biosynthetic pathways and to their biosynthetic relationships, even when defined by the non-amino acid molecules that are their precursors.
It is re-observed that the first amino acids to evolve along these biosynthetic pathways are predominantly those codified by codons of the type GNN, and this observation is found to be statistically significant. Furthermore, the close biosynthetic relationships between the sibling amino acids Ala-Ser, Ser-Gly, Asp-Glu, and Ala-Val are not random in the genetic code table and reinforce the hypothesis that the biosynthetic relationships between these six amino acids played a crucial role in defining the very earliest phases of genetic code origin.
All this leads to the hypothesis that there existed a code, GNS, reflecting the biosynthetic relationships between these six amino acids which, as it defines the very earliest phases of genetic code origin, removes the main difficulty of the coevolution theory. Furthermore, it is here discussed how this code might have naturally led to the code codifying only for the domains of the codons of precursor amino acids, as predicted by the coevolution theory. Finally, the hypothesis here suggested also removes other problems of the coevolution theory, such as the existence for certain pairs of amino acids with an unclear biosynthetic relationship between the precursor and product amino acids and the collocation of Ala between the amino acids Val and Leu belonging to the pyruvate biosynthetic family, which the coevolution theory considered as belonging to different biosyntheses.
This article was reviewed by Rob Knight, Paul Higgs (nominated by Laura Landweber), and Eugene Koonin.
遗传密码起源的共同进化理论认为，遗传密码是氨基酸之间生物合成关系的印记。然而，该理论似乎并未赋予沿着能量代谢途径进化的最早氨基酸之间的生物合成关系以作用。因此，共同进化理论无法清晰界定遗传密码起源的最早期阶段。为了消除这一困难，我在此提出对共同进化理论的一种扩展，即赋予沿着这些生物合成途径进化的首批氨基酸及其生物合成关系以关键作用，即便这些关系是由作为其前体的非氨基酸分子所定义的。
再次观察到，沿着这些生物合成途径进化的首批氨基酸主要是由GNN型密码子编码的那些氨基酸，并且这一观察结果具有统计学意义。此外，在遗传密码表中，Ala-Ser、Ser-Gly、Asp-Glu和Ala-Val这几对同源氨基酸之间紧密的生物合成关系并非随机的，这强化了以下假说：这六种氨基酸之间的生物合成关系在界定遗传密码起源的最早期阶段发挥了关键作用。
所有这些都引出了这样一个假说，即存在一种GNS密码，它反映了这六种氨基酸之间的生物合成关系，由于它界定了遗传密码起源的最早期阶段，因而消除了共同进化理论的主要困难。此外，本文还讨论了这种密码如何可能自然地导致只对前体氨基酸密码子结构域进行编码的密码，正如共同进化理论所预测的那样。最后，这里提出的假说还消除了共同进化理论的其他问题，比如某些氨基酸对之间前体氨基酸和产物氨基酸的生物合成关系不明确，以及属于丙酮酸生物合成家族的Ala在Val和Leu这两种氨基酸之间的排列，而共同进化理论认为它们属于不同的生物合成途径。
本文由罗布·奈特、保罗·希格斯（由劳拉·兰德韦伯提名）和尤金·库宁评审。
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