The role of location propagation for translocon complex relocation during eukaryogenesis

In all domains of life, the translationally-active ribosome-translocon complex inserts nascent transmembrane proteins into, and processes and transports signal peptide-containing proteins across, membranes1,2. Eukaryotic translocons are anchored in the endoplasmic reticulum, while the prokaryotic complexes reside in cell membranes. DNA sequence analyses indicate that the eukaryotic Sec61/OST/TRAP translocon is inherited from an Asgard archaea ancestor3,4. However, the mechanism for translocon migration from a peripheral membrane to an internal cellular compartment (the proto-endoplasmic reticulum) during eukaryogenesis is unknown. Here we show that Asgard and eukaryotic ribosome-translocon complexes are intercompatible. We find that fluorescently-tagged Asgard translocon proteins from Candidatus Prometheoarchaeum syntrophicum strain MK-D15, a Lokiarchaeon confirmed to contain no internal cellular membranes, are targeted to the eukaryotic endoplasmic reticulum on ectopic expression. Our data demonstrate that the location of existing ribosome-translocon complexes, at the protein level, determines the future placement of yet to be translated translocon subunits. This principle predicts that during eukaryogenesis, under positive selection pressure, the relocation of a few translocon complexes to the proto-endoplasmic reticulum will have propagated the new translocon location, leading to their loss from the cell membrane.