Fig. 2.

Proposed scenario for the origin and early evolution of DNA replication and transcription. a Evolution of cellular (top) and viral (bottom) polymerases from a double-psi beta-barrel (DPBB) and RNA recognition motif (RRM)-containing proteins, respectively. The first DPBB- and RRM-based polymerases have likely originated in protocells at the earliest stages of evolution, preceding the emergence of the Last Universal Cellular Ancestor (pre-LUCA); polymerases responsible for LUCA’s genome replication and transcription evolved from a common ancestor. DPBB-based RNAPs were exchanged between the cellular and viral worlds in both directions. b Scenario for the evolution of DNA replication machineries in the 3 domains of life. The multiple forms of PolB that are present in both archaea and eukaryotes are not shown for the sake of simplicity. Different domains and subunits are indicated with various shapes and colors. Yellow star indicates an active exonuclease domain. Note that DP1 subunit in the eukaryotic DNAPs is an inactivated exonuclease. DPBB is indicated with a triple hashtag symbol, whereas palm (RRM) domains are indicated with arrows. (e)RdRP, (eukaryotic) RNA-dependent RNA polymerase; (ss)RNAP, (single-subunit) DNA-dependent RNA polymerase; RT, reverse transcriptase; PolA, B, C, and D, DNA polymerases of families A, B, C, and D; DP1, small subunit of PolD with exonuclease activity; DP2, large subunit of PolD with DNA polymerase activity; RH, ribonuclease H domain; exo, exonuclease domain; CTD, C-terminal domain; PIP, PCNA-interacting motif; MGE, mobile genetic elements