New evidence for the genomic tag hypothesis: archaeal CCA-adding enzymes and tDNA substrates.

Abstract

The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyl transferase] catalyzes the addition and regeneration of the 3’ terminal CCA sequence of tRNAs. The enzyme adds the sequence CCA one nucleotide at a time to the 3’-terminus of tRNA, using CTP and ATP as precursors, and can utilize tRNA substrates lacking one, two, or all three terminal nucleotides. The 3’ terminal CCA is encoded in all tRNA genes of some eubacteria (Escherichia coli, Mycoplasma genitalium), in about half the tRNA genes of other eubacteria (Bacillus subtilis) and Archaea (l-3), but only very rarely in eukaryotes (4). The CCA-adding enzyme thus functions mainly as a “repair” enzyme in a subset of eubacteria, but as an essential biosynthetic enzyme in most eubacteria, as well as in all known Archaea and eukaryotes. As expected, the enzyme is essential for viability in the budding yeast Saccharomyces cerevisiae where CCA is not encoded (5), but it is partially dispensable in E. coli where CCA is encoded (6). We have argued that molecular structure and function can provide compelling evidence for descent from a common ancestor, and that careful inspection of the structure and function of contemporary biological molecules can yield highly informative, intellectually rigorous, functional phylogenies despite the absence of conventionally quantifiable traits. Based on the many different roles that tRNA is known to play in RNA and DNA replication, we have presented one such functional phylogeny showing how these diverse roles of tRNA in replication are likely to have evolved from an RNA to the DNA world (7-10; and see Weiner and