The animal sialyltransferases, which catalyze the transfer of sialic acid to the glycan moiety of glycoconjugates, are subdivided into four families: ST3Gal, ST6Gal, ST6GalNAc and ST8Sia, based on acceptor sugar specificity and glycosidic linkage formed. Despite low overall sequence identity between each sialyltransferase family, all sialyltransferases share four conserved peptide motifs (L, S, III and VS) that serve as hallmarks for the identification of the sialyltransferases. Currently, twenty subfamilies have been described in mammals and birds. Examples of the four sialyltransferase families have also been found in invertebrates. Focusing on the ST8Sia family, we investigated the origin of the three groups of α2,8-sialyltransferases demonstrated in vertebrates to carry out poly-, oligo- and mono-α2,8-sialylation.

Cell surface of eukaryotic cells is covered with a wide variety of sialylated molecules involved in diverse biological processes and taking part in cell–cell interactions. Although the physiological relevance of these sialylated glycoconjugates in vertebrates begins to be deciphered, the origin and evolution of the genetic machinery implicated in their biosynthetic pathway are poorly understood. Among the variety of actors involved in the sialylation machinery, sialyltransferases are key enzymes for the biosynthesis of sialylated molecules. This review focus on β-galactoside α2,3/6-sialyltransferases belonging to the ST3Gal and ST6Gal families. We propose here an outline of the evolutionary history of these two major ST families. Comparative genomics, molecular phylogeny and structural bioinformatics provided insights into the functional innovations in sialic acid metabolism and enabled to explore how ST-gene function evolved in vertebrates.

Sialyltransferases are key enzymes in the biosynthesis of sialoglycoconjugates that catalyze the transfer of sialic residue from its activated form to an oligosaccharidic acceptor. β-Galactoside α2,6-sialyltransferases ST6Gal I and ST6Gal II are the two unique members of the ST6Gal family described in higher vertebrates. The availability of genome sequences enabled the identification of more distantly related invertebrates' st6gal gene sequences and allowed us to propose a scenario of their evolution. Using a phylogenomic approach, we present further evidence of an accelerated evolution of the st6gal1 genes both in their genomic regulatory sequences and in their coding sequence in reptiles, birds, and mammals known as amniotes, whereas st6gal2 genes conserve an ancestral profile of expression throughout vertebrate evolution.

The formation of β1,3-linkages on animal glycoconjugates is catalyzed by a subset of β1,3-glycosyltransferases grouped in the Carbohydrate-Active enZYmes family glycosyltransferase-31 (GT31). This family represents an extremely diverse set of β1,3-N-acetylglucosaminyltransferases [B3GNTs and Fringe β1,3-N-acetylglucosaminyltransferases], β1,3-N-acetylgalactosaminyltransferases (B3GALNTs), β1,3-galactosyltransferases [B3GALTs and core 1 β1,3-galactosyltransferases (C1GALTs)], β1,3-glucosyltransferase (B3GLCT) and β1,3-glucuronyl acid transferases (B3GLCATs or CHs). The mammalian enzymes were particularly well studied and shown to use a large variety of sugar donors and acceptor substrates leading to the formation of β1,3-linkages in various glycosylation pathways. In contrast, there are only a few studies related to other metazoan and lower vertebrates GT31 enzymes and the evolutionary relationships of these divergent sequences remain obscure. In this study, we used bioinformatics approaches to identify more than 920 of putative GT31 sequences in Metazoa, Fungi and Choanoflagellata revealing their deep ancestry. Sequence-based analysis shed light on conserved motifs and structural features that are signatures of all the GT31. We leverage pieces of evidence from gene structure, phylogenetic and sequence-based analyses to identify two major subgroups of GT31 named Fringe-related and B3GALT-related and demonstrate the existence of 10 orthologue groups in the Urmetazoa, the hypothetical last common ancestor of all animals. Finally, synteny and paralogy analysis unveiled the existence of 30 subfamilies in vertebrates, among which 5 are new and were named C1GALT2, C1GALT3, B3GALT8, B3GNT10 and B3GNT11. Altogether, these various approaches enabled us to propose the first comprehensive analysis of the metazoan GT31 disentangling their evolutionary relationships.