PT  - JOURNAL ARTICLE
AU  - Sota Yagi
AU  - Aditya K. Padhi
AU  - Jelena Vucinic
AU  - Sophie Barbe
AU  - Thomas Schiex
AU  - Reiko Nakagawa
AU  - David Simoncini
AU  - Kam Y. J. Zhang
AU  - Shunsuke Tagami
TI  - Seven amino acid types suffice to reconstruct the core fold of RNA polymerase
AID  - 10.1101/2021.02.22.432383
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.22.432383
4099  - http://biorxiv.org/content/early/2021/02/23/2021.02.22.432383.short
4100  - http://biorxiv.org/content/early/2021/02/23/2021.02.22.432383.full
AB  - The extant complex proteins must have evolved from ancient short and simple ancestors. Nevertheless, how such prototype proteins emerged on the primitive earth remains enigmatic. The double-psi beta-barrel (DPBB) is one of the oldest protein folds and conserved in various fundamental enzymes, such as the core domain of RNA polymerase. Here, by reverse engineering a modern DPBB domain, we reconstructed its evolutionary pathway started by “interlacing homo- dimerization” of a half-size peptide, followed by gene duplication and fusion. Furthermore, by simplifying the amino acid repertoire of the peptide, we successfully created the DPBB fold with only seven amino acid types (Ala, Asp, Glu, Gly, Lys, Arg, and Val), which can be coded by only GNN and ARR (R = A or G) codons in the modern translation system. Thus, the DPBB fold could have been materialized by the early translation system and genetic code.Competing Interest StatementThe authors have declared no competing interest.