The multiple evolutionary origins of the eukaryotic N-glycosylation pathway

Abstract

BackgroundThe N-glycosylation is an essential protein modification taking place in the membranes of the endoplasmic reticulum (ER) in eukaryotes and the plasma membranes in archaea. It shares mechanistic similarities based on the use of polyisoprenol lipid carriers with other glycosylation pathways involved in the synthesis of bacterial cell wall components (e.g. peptidoglycan and teichoic acids). Here, a phylogenomic analysis was carried out to examine the validity of rival hypotheses suggesting alternative archaeal or bacterial origins to the eukaryotic N-glycosylation pathway.ResultsThe comparison of several polyisoprenol-based glycosylation pathways from the three domains of life shows that most of the implicated proteins belong to a limited number of superfamilies. The N-glycosylation pathway enzymes are ancestral to the eukaryotes, but their origins are mixed: Alg7, Dpm and maybe also one gene of the glycosyltransferase 1 (GT1) superfamily and Stt3 have proteoarchaeal (TACK superphylum) origins; alg2/alg11 may have resulted from the duplication of the original GT1 gene; the lumen glycosyltransferases were probably co-opted and multiplied through several gene duplications during eukaryogenesis; Alg13/Alg14 are more similar to their bacterial homologues; and Alg1, Alg5 and a putative flippase have unknown origins.ConclusionsThe origin of the eukaryotic N-glycosylation pathway is not unique and less straightforward than previously thought: some basic components likely have proteoarchaeal origins, but the pathway was extensively developed before the eukaryotic diversification through multiple gene duplications, protein co-options, neofunctionalizations and even possible horizontal gene transfers from bacteria. These results may have important implications for our understanding of the ER evolution and eukaryogenesis.ReviewersThis article was reviewed by Pr. Patrick Forterre and Dr. Sergei Mekhedov (nominated by Editorial Board member Michael Galperin).Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-016-0137-2) contains supplementary material, which is available to authorized users.

Early evolution of polyisoprenol biosynthesis and the origin of cell walls

“…The proteins in these families are responsible for the transfer of soluble monosaccharides to polyisoprenol phosphate lipid carriers in bacterial peptidoglycan synthesis (Mohammadi et al, 2007) and archaeal S-layer protein N -glycosylation (Meyer & Albers, 2013). If we sum up the results presented here and those about glycosyltransferases (Lombard, 2016), it is tempting to say that the cenancestor could have been able to use its HPT and MurG homologues to synthesize an oligosaccharide on a Bac-P lipid carrier. The question that remains open is the final acceptor of that hypothetical cenancestral oligosaccharide, as that is the element that would define the nature of the putative cenancestral cell wall.…”

“…Although the mechanism that provides this molecule to the periplasmic phosphatases remains unknown (Chang et al, 2014; Manat et al, 2015), the possibility that UppP homologues may also be ancestral to both prokaryotic domains similarly suggests that the cenancestor could even have been able to synthesize some sort of Bac-P. Polyisoprenols may carry out pleiotropic functions (Cantagrel & Lefeber, 2011; Hartley & Imperiali, 2012), but their most notorious role is as lipid carriers in a number of glycosylation pathways (Lombard, 2016). In prokaryotes, these glycosylations are systematically related to the synthesis of cell wall components, so it is reasonable to postulate that hypothetical cenancestral polyisoprenols may have played the role of lipid carriers in early glycosylation mechanisms, possibly related to cell wall synthesis.…”

“…Interestingly, the presence of at least two promising glycosyltransferase superfamilies (HPT and MurG) has been inferred in the cenancestor (Lombard, 2016). The proteins in these families are responsible for the transfer of soluble monosaccharides to polyisoprenol phosphate lipid carriers in bacterial peptidoglycan synthesis (Mohammadi et al, 2007) and archaeal S-layer protein N -glycosylation (Meyer & Albers, 2013).…”

“…Despite the stunning diversity that exists among prokaryotic cell envelopes, the synthesis of many of their main components (e.g.,  N -or O -glycosylated S-layer proteins, peptidoglycan, O -antigen LPS, teichoic acids, exopolysaccharides) relies on comparable glycosylation pathways (Hartley & Imperiali, 2012; Lombard, 2016). These pathways are all located in the cell membranes, are mediated by similar lipid carriers and have the same orientation across the membrane.…”

“…The eukaryotic protein N -glycosylation also meets these criteria, although it takes place in the ER membranes instead of the plasma membranes. The proteins involved in these glycosylation pathways belong to a small number of protein superfamilies, some of which could be traced back to the cenancestor (Lombard, 2016). The large diversity of the glycosylation pathways makes it difficult to untangle the specific evolutionary relationships that exist among them but, despite their differences, the prokaryotic cell wall synthesis mechanisms have at least one element in common: they all use polyisoprenol phosphate lipid carriers (Hartley & Imperiali, 2012).…”