Massimo Di Giulio

The definition of the node of the last universal common ancestor (LUCA) is justified in a topology of the unrooted universal tree. This definition allows previous analyses based on paralogous proteins to be extended to orthologous ones. In particular, the use of a thermophily index (based on the amino acids’ propensity to enter the [hyper] thermophile proteins more frequently) and its correlation with the optimal growth temperature of the various organisms allow inferences to be made on the habitat in which the LUCA lived. The reconstruction of ancestral sequences by means of the maximum likelihood method and their attribution to the set of mesophilic or hyperthermophilic sequences have led to the following conclusions: the LUCA was a hyperthermophile “organism,” as were the ancestors of the Archaea and Bacteria domains, while the ancestor of the Eukarya domain was a mesophile. These conclusions are independent of the presence of hyperthermophile bacteria in the sample of sequences used in the analysis and are therefore independent of whether or not these are the first lines of divergence in the Bacteria domain, as observed in the topology of the universal tree of ribosomal RNA. These conclusions are thus more easily understood under the hypothesis that the origin of life took place at a high temperature.

A review of the most significant contributions on the early phases of genetic code origin is presented. After stressing the importance of the key intermediary role played in protein synthesis, by...

Ronneberg et al. (Proc Natl Acad Sci USA 97:13690–13695, 2000) recently suggested abandoning the coevolution theory of genetic code origin on the basis of two pieces of evidence. They (1) criticize the use of several pairs of amino acids in a precursor–product relationship to support this theory and (2) suggest a new set of codes in which to investigate the statistical bases of the coevolution theory, reaching the conclusion that this theory is not statistically validated in this set. In this paper I critically analyze the robustness of these conclusions. Observations and arguments lead to the belief that the pairs of amino acids in a precursor–product relationship originally used by the coevolution theory are such, or may at least be interpreted as such, and are therefore a manifestation of this theory. Furthermore, the new set of codes that Ronneberg et al. suggest is open to criticism and is thus substituted by the set of amino acid permutation codes, in which even the pairs of amino acids they favor end up by supporting the coevolution theory. Overall, the analysis seems to show that the paper by Ronneberg et al. is of minor scientific value while the coevolution theory seems to be one of the best theories at our disposal for explaining the evolutionary organisation of the genetic code and is, contrary to their claims, statistically well validated.

We consider a model of the origin of genetic code organization incorporating the biosynthetic relationships between amino acids and their physicochemical properties. We study the behavior of the genetic code in the set of codes subject both to biosynthetic constraints and to the constraint that the biosynthetic classes of amino acids must occupy only their own codon domain, as observed in the genetic code. Therefore, this set contains the smallest number of elements ever analyzed in similar studies. Under these conditions and if, as predicted by physicochemical postulates, the amino acid properties played a fundamental role in genetic code organization, it can be expected that the code must display an extremely high level of optimization. This prediction is not supported by our analysis, which indicates, for instance, a minimization percentage of only 80%. These observations can therefore be more easily explained by the coevolution theory of genetic code origin, which postulates a role that is important but not fundamental for the amino acid properties in the structuring of the code. We have also investigated the shape of the optimization landscape that might have arisen during genetic code origin. Here, too, the results seem to favor the coevolution theory because, for instance, the fact that only a few amino acid exchanges would have been sufficient to transform the genetic code (which is not a local minimum) into a much better optimized code, and that such exchanges did not actually take place, seems to suggest that, for instance, the reduction of translation errors was not the main adaptive theme structuring the genetic code.