The very early evolution of protein translocation across membranes.

Aj Harris,Aaron David Goldman,Dan S Tawfik

doi:10.1371/journal.pcbi.1008623

Abstract

In this study, we used a computational approach to investigate the early evolutionary history of a system of proteins that, together, embed and translocate other proteins across cell membranes. Cell membranes comprise the basis for cellularity, which is an ancient, fundamental organizing principle shared by all organisms and a key innovation in the evolution of life on Earth. Two related requirements for cellularity are that organisms are able to both embed proteins into membranes and translocate proteins across membranes. One system that accomplishes these tasks is the signal recognition particle (SRP) system, in which the core protein components are the paralogs, FtsY and Ffh. Complementary to the SRP system is the Sec translocation channel, in which the primary channel-forming protein is SecY. We performed phylogenetic analyses that strongly supported prior inferences that FtsY, Ffh, and SecY were all present by the time of the last universal common ancestor of life, the LUCA, and that the ancestor of FtsY and Ffh existed before the LUCA. Further, we combined ancestral sequence reconstruction and protein structure and function prediction to show that the LUCA had an SRP system and Sec translocation channel that were similar to those of extant organisms. We also show that the ancestor of Ffh and FtsY that predated the LUCA was more similar to FtsY than Ffh but could still have comprised a rudimentary protein translocation system on its own. Duplication of the ancestor of FtsY and Ffh facilitated the specialization of FtsY as a membrane bound receptor and Ffh as a cytoplasmic protein that could bind nascent proteins with specific membrane-targeting signal sequences. Finally, we analyzed amino acid frequencies in our ancestral sequence reconstructions to infer that the ancestral Ffh/FtsY protein likely arose prior to or just after the completion of the canonical genetic code. Taken together, our results offer a window into the very early evolutionary history of cellularity.

Highlights

The emergence of cellular organisms from non-cellular replicators is considered one of the major transitions, or key innovations, in evolutionary history [1] that may have been the prerequisite for the earliest speciation events [2] and for subsequent colonization of all the habitable environments on Earth [3,4]
One of these proteins is a cytosolic protein known as Ffh in Bacteria and SRP54 in Archaea and Eukarya that binds a signal sequence in a nascent protein and guides the ribosome synthesizing the protein to the membrane [5,6,7]
We used ancestral sequence reconstructions combined with protein function prediction to show that the ancestral Ffh and FtsY protein that predated the last universal common ancestor (LUCA) potentially arose before the completion of the genetic code, but that it likely contained many functional components of the modern signal recognition particle (SRP) system allowing it to facilitate a rudimentary form of protein translocation and secretion across cell membranes

Summary

Author summary

Cellularity is an ancient, fundamental organizing principle of life. Central to cellularity is the cell membrane, which separates a cell from the outside environment. Embedding proteins into membranes and secreting proteins across membranes is an essential aspect of cellularity, not to mention an essential aspect of life itself. One cellular system that accomplishes embedding proteins into membranes and secreting proteins across membranes is the signal recognition particle (SRP) system. To study the SRP system and the central protein of the Sec channel, SecY, in early life, we reconstructed evolutionary trees from protein sequences. Based on these trees, we infer that the last universal common ancestor (LUCA) of life had an SRP system and SecY channel that were similar to those in extant organisms, while an earlier ancestor of the LUCA possessed a more rudimentary system for embedding and secreting proteins. The ancestral Ffh/FtsY protein probably arose prior to or soon after the final amino acids were added to the standard genetic code

Introduction

Results and discussion

Materials and methods