ABSTRACT
KsgA has had a remarkable path o f discovery and study over the past 40 years, yet fundamental
questions remain. One o f the deepest and therefore most vexing, questions is why has this protein been universally conserved. Given that the dimethyladenosines o f small subunit rRNA have broad phylogenetic penetration, we can assume that the last universal common ancestor (LUCA) o f all present-day life had a KsgA-like protein that performed analogous chemistry. However, despite the conservation o f the tandem dimethyladenosines, neither E. coli nor S. cerevisiae suffers sig nificantly when the methyl groups are absent. If LUCA were likewise ambivalent to the presence of the dimethyladenosines, then it is hard to imagine that the methylated adenosines themselves provided the overwhelming selective advantage to preserve KsgA/Dim l. In the two organisms where D im l and KsgA function has been studied, the eukaryote S. cerevisiae and the bacterium E. coli these enzymes are involved in broader roles in ribosome biogenesis-eukaryotic D im l as an essential member o f the processome and the bacterial KsgA as a gate-keeper to assure biogenic fidelity. Yet here there appears to be litde overlap between the nonmethylation functions o f KsgA and Dim 1, making common ancestry from LUCA based on a nonmethyltransferase function dif ficult to envision. It is possible that the observed adaptability o f the KsgA/Dim 1 protein to evolve new functions will ultimately obscure the role that the LUCA KsgA/Dim l played in ribosomal biogenesis. Perhaps the best understanding o f a nonmethyltransferase unified function, if any, will come when ribosome biogenesis in phylogenetically distant organisms is understood at the molecular level. In this way we can let an understanding of ribosome biogenesis inform us o f the function o f Dim l/KsgA, rather than the other way around.
