Insights into DNA replication from the third domain of life

The discovery of the Archaea (1), the third domain of life, has reinvigorated efforts to understand the phylogenetic relationships among all forms of life. It is therefore not surprising that the recent completion of four archaeal genomes (2–5) created a flurry of excitement among biologists (Genetics, Vol. 152). A comparison of genome sequences reveals that the prokaryotes, Archaea and Bacteria, have closer similarities in their metabolic processes, but Archaea and Eukarya have more similarities in their information processing machineries (DNA replication, transcription, and translation) (6, 7). If this initial observation were supported by further biochemical analyses, then it would suggest that Archaea and Bacteria diverged before the evolution of mechanisms that substantially increased the fidelity of information transfer. That pressure for accuracy may have increased as genomes became more and more complex. Furthermore, it would suggest Archaea and Eukarya share a common ancestor more recently than either shares with Bacteria (Fig. 1). This observation has drawn intense interests from biochemists who have long been battling with the complexities of eukaryal biology. If Archaea embody a more primitive form of the highly evolved Eukarya, then simplified models for complex systems of Eukarya may be found in Archaea. Indeed, a composite of the putative replication proteins identified from four archaeal genomes supports this view (Table 1) (7). This rationale provided the motivation for the biochemical characterization of the Methanobacterium thermoautotrophicum MCM protein.