Nucleic Acids Research, Vol 27, Issue 17 3389-3401, Copyright © 1999 by Oxford University Press
DD Leipe, L Aravind and EV Koonin
DNA replication is central to all extant cellular organisms. There are
substantial functional similarities between the bacterial and the
archaeal/eukaryotic replication machineries, including but not limited to
defined origins, replication bidirectionality, RNA primers and leading and
lagging strand synthesis. However, several core components of the bacterial
replication machinery are unrelated or only distantly related to the
functionally equivalent components of the archaeal/eukaryotic replication
apparatus. This is in sharp contrast to the principal proteins involved in
transcription and translation, which are highly conserved in all divisions
of life. We performed detailed sequence comparisons of the proteins that
fulfill indispensable functions in DNA replication and classified them into
four main categories with respect to the conservation in bacteria and
archaea/eukaryotes: (i) non-homologous, such as replicative polymerases and
primases; (ii) containing homologous domains but apparently non-
orthologous and conceivably independently recruited to function in
replication, such as the principal replicative helicases or proofreading
exonucleases; (iii) apparently orthologous but poorly conserved, such as
the sliding clamp proteins or DNA ligases; (iv) orthologous and highly
conserved, such as clamp-loader ATPases or 5'-- >3' exonucleases (FLAP
nucleases). The universal conservation of some components of the DNA
replication machinery and enzymes for DNA precursor biosynthesis but not
the principal DNA polymerases suggests that the last common ancestor (LCA)
of all modern cellular life forms possessed DNA but did not replicate it
the way extant cells do. We propose that the LCA had a genetic system that
contained both RNA and DNA, with the latter being produced by reverse
transcription. Consequently, the modern-type system for double-stranded DNA
replication likely evolved independently in the bacterial and
archaeal/eukaryotic lineages.
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Did DNA replication evolve twice independently?
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