Sir,
Davis (1) concurs with the inter-relatedness of genetic code and amino acid biosynthesis evolution as proposed by the coevolution theory (CET) of the genetic code, (2,3) but argues against one of the postulates of CET, namely the formation of Asp-tRNA Asn and Glu-tRNA Gln during genetic code development. This postulate requires that Asp-tRNA synthetase (AspRS) charges with Asp the tRNAs earmarked for both Asp and Asn, and Glu-tRNA synthetase (GluRS) charges with Glu the tRNAs earmarked for both Glu and Gln. Without such dual charging, the contiguities identified by CET between the precursor-product codons of the Asp-Thr, Asp-Lys, Glu-Arg and Glu-Pro precursor-product pairs could not be established.
Although neither E. coli nor yeast AspRS aspartylates tRNA Asn , dual Asp-charging of both tRNA Asn and tRNA Asp by AspRS is needed by any organism that does not possess an AsnRS. A majority of the 52 prokaryotic genomes on the universal tRNA tree, (3) including 12/18 archaeal and 15/34 bacterial species, are in fact devoid of AsnRS, and utilize AspRS to produce Asp-tRNA Asn , which in turn serves as precursor in the pretran synthesis of Asn-tRNA Asn . Likewise, 18/18 archaeal and 21/34 bacterial species lack GlnRS, and have to utilize GluRS to produce Glu-tRNA Gln for subsequent pretran synthesis to yield Gln-tRNA Gln . Methanopyrus, which on the basis of the extreme primitivity of its tRNA and aaRS genes is closest to the Last Universal Common Ancestor or LUCA at the root of life, (4,5) is among the species that possess neither AsnRS nor GlnRS. This indicates that the lack of AsnRS and GlnRS is a primitive biological character, and the formation of Asp-tRNA Asn and Glu-tRNA Gln would be prevalent during genetic code evolution prior to the emergence of LUCA.
The argument given by Davis to preclude categorically the dual Asp-charging of tRNA Asp and tRNA Asn by AspRS, built on structural dissimilarities between some tRNA Asp and tRNA Asn , overlooks variations between AspRS from different organisms with regard to how they select tRNA substrates. (6) It is valid for organisms, such as E. coli and yeast, that possess AsnRS and have no capacity to amidate Asp-tRNA Asn , where any formation of Asp-tRNA Asn would give rise to translational