A model for genesis of transcription systems

Abstract

Repeating sequences generated from RNA gene fusions/ligations dominate ancient life, indicating central importance of building structural complexity in evolving biological systems. A simple and coherent story of life on earth is told from tracking repeating motifs that generate α/β proteins, 2-double-Ψ-β-barrel (DPBB) type RNA polymerases (RNAPs), general transcription factors (GTFs), and promoters. A general rule that emerges is that biological complexity that arises through generation of repeats is often bounded by solubility and closure (i.e., to form a pseudo-dimer or a barrel). Because the first DNA genomes were replicated by DNA template-dependent RNA synthesis followed by RNA template-dependent DNA synthesis via reverse transcriptase, the first DNA replication origins were initially 2-DPBB type RNAP promoters. A simplifying model for evolution of promoters/replication origins via repetition of core promoter elements is proposed. The model can explain why Pribnow boxes in bacterial transcription (i.e., (-12)TATAATG(-6)) so closely resemble TATA boxes (i.e., (-31)TATAAAAG(-24)) in archaeal/eukaryotic transcription. The evolution of anchor DNA sequences in bacterial (i.e., (-35)TTGACA(-30)) and archaeal (BRE(up); BRE for TFB recognition element) promoters is potentially explained. The evolution of BRE(down) elements of archaeal promoters is potentially explained.

Keywords: LECA (the last eukaryotic common ancestor); LUCA (the last universal common cellular ancestor); RIFT barrels; RNA polymerase; Rossmann folds; TATA-binding protein (TBP); TIM barrels; cradle-loop barrel metafold; double-Ψ−β-barrels; general transcription factors; replication; the carboxy terminal domain (CTD) of RNA polymerase II; transcription; transcription factor B (TFB); α/β protein folds; σ factors.

Figure 1.

α/β folds are simple (β−α)_n repeat proteins. The pie chart indicates that ∼25% of all structures in the RCSB protein data bank are α/β fold proteins. A model is shown for evolution of TIM barrels (β−α)₈ and Rossmann folds (β−α)₈.

Figure 2.

Cradle-loop barrels: RIFT barrels and DPBBs. A) PHS018 RIFT barrel (PDB 2GLW). B) VatN-N DPBB (PDB 1CZ4) (a AAA+ ATPase). C) RNAP β’ DPBB (PDB 4OIO). D) RNAP β DPBB (PDB 4OIO). Small blue arrows indicate α1 and α2. Small black arrows in the schematics indicate insertions in RNAP DPBBs. Conserved GD motifs and possible GD relics in RNAP DPBBs are indicated in sphere representation. A signature motif of RNAPs, NADFDGD that binds Mg-I (Mg-A), ends in a conserved GD box. Molecular graphics images were made using Pymol (https://www.pymol.org/).

Figure 3.

2-DPBB type RNAPs. A) S. cerevisiae (yeast) RNAP III (a homology model). The 2-DPBBs border the active site. B) Thermus thermophilus RNAP catalytic core including 2-DPBBs, the SBHM, the bridge helix (BH) and trigger loop (TL) (PDB 2O5J) (a DNA template-dependent RNAP). C) N. crassa (mold) interfering RNAP catalytic core including 2-DPBBs, BH and TL (PDB 2J7N) (a RNA template-dependent RNAP).

Figure 4.

A model for evolution of bacterial σ factors and archaeal TFB from a 4-HTH primordial initiation factor at LUCA. Classic σ homology regions overlap with HTH_1-4.

Figure 5.

Bacterial σ factor interactions with promoter DNA in initiating complexes with an open transcription bubble (PDB 4XLN). RNAP was removed from the image in order to visualize σ (green except at HTH motifs) interactions to promoter DNA. HTH units are colored blue (H1), magenta (H2) and orange (H3; N-terminal end only). Only σ HTH₄, HTH₃ and HTH₂ were colored. In this view, HTH₁ is obscured by HTH₂. To locate the RNAP active site, RNA and Mg-I are shown.

Figure 6.

A model for a LUCA promoter sequence generated as an AT-rich repeat of TATAAAAG boxes and BREs. The repeat sequence simplifies to an archaeal and a bacterial promoter.

Figure 7.

A model for primordial GTFs on a LUCA promoter and for radiation to archaea and bacteria. The model was constructed by superimposing 3-PDB 1AIS structures (archaeal TBP-TFB-promoter DNA). The 4-HTH primordial initiation factor was generated by sequential alignment of 3 2-HTH repeats of TFB HTH₁-(HTH₂/HTH₁)-(HTH₂/HTH₁)-HTH₂. Bacterial systems are posited to have lost TBP and to have made the σ factor more strongly coevolved with promoter DNA and RNAP than in archaea or at LUCA.