Missing-link fold reveals the evolutionary pathway between RNA polymerase and ribosomal proteins

Abstract

Numerous molecular machines are required to drive the central dogma of molecular biology. However, the means by which such numerous proteins emerged in the early evolutionary stage of life remains enigmatic. Many of them possess small β-barrel folds with different topologies, represented by DPBB conserved in DNA and RNA polymerases, and RIFT, OB, and SH3 in ribosomal proteins. Here, we discovered that the previously reconstructed ancient DPBB sequence could also adopt a novel β-barrel fold named DZBB, which shares similarities with RIFT and OB. Indeed, DZBB could be transformed into them through simple engineering experiments. Furthermore, the OB designs could be converted into SH3 by circular-permutation. These results indicate that these β-barrels diversified quickly from a common ancestor at the beginning of the central dogma evolution.