The very early evolution of protein translocation across membranes


Cellularity is an ancient, fundamental organizing principle of life. Central to cellularity is the cell membrane, which separates a cell from the outside environment. Cell membranes contain proteins that perform a range of functions including transport of compounds across the membrane barrier, sensing the external environment, and performing certain metabolic activities that must occur in proximity to the membrane. Therefore, 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. The SRP system has a core consisting of the proteins, FtsY and Ffh, which derive from a single FtsY/Ffh ancestral protein. The system is also associated with a protein-based passageway, the Sec channel, for embedding proteins within the membrane or allowing them to pass through it. 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. Moreover, the ancestral Ffh/FtsY protein probably arose prior to or soon after the final amino acids were added to the standard genetic code.

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.


Public Library Science

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PLOS Computational Biology



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Signal recognition particle, Multiple sequence alignment, Bayesian phylogenetic inference, Structural basis, Gtpase activation, Alpha subunit, Amino acids, 4.55 RNA, SRP, Database





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