The animal sialyltransferases are Golgi type II transmembrane glycosyltransferases. Twenty distinct sialyltransferases have been identified in both human and murine genomes. These enzymes catalyze transfer of sialic acid from CMP-Neu5Ac to the glycan moiety of glycoconjugates. Despite low overall identities, they share four conserved peptide motifs [L (large), S (small), motif III, and motif VS (very small)] that are hallmarks for sialyltransferase identification. We have identified 155 new putative genes in 25 animal species, and we have exploited two lines of evidence: (1) sequence comparisons and (2) exon-intron organization of the genes. An ortholog to the ancestor present before the split of ST6Gal I and II subfamilies was detected in arthropods. An ortholog to the ancestor present before the split of ST6GalNAc III, IV, V, and VI subfamilies was detected in sea urchin. An ortholog to the ancestor present before the split of ST3Gal I and II subfamilies was detected in ciona, and an ortholog to the ancestor of all the ST8Sia was detected in amphioxus. Therefore, single examples of the four families (ST3Gal, ST6Gal, ST6GalNAc, and ST8Sia) have appeared in invertebrates, earlier than previously thought, whereas the four families were all detected in bony fishes, amphibians, birds, and mammals. As previously hypothesized, sequence similarities among sialyltransferases suggest a common genetic origin, by successive duplications of an ancestral gene, followed by divergent evolution. Finally, we propose predictions on these invertebrates sialyltransferase-related activities that have not previously been demonstrated and that will ultimately need to be substantiated by protein expression and enzymatic activity assays.
On the basis of function and sequence similarities, the vertebrate fucosyltransferases can be classified into three groups: alpha-2-, alpha-3-, and alpha-6-fucosyltransferases. Thirty new putative fucosyltransferase genes from invertebrates and bacteria and six conserved peptide motifs have been identified in DNA and protein databanks. Two of these motifs are specific of alpha-3-fucosyltransferases, one is specific of alpha-2-fucosyltransferases, another is specific of alpha-6-fucosyltransferases, and two are shared by both alpha-2- and alpha-6-fucosyltranserases. Based on these data, literature data, and the phylogenetic analysis of the conserved peptide motifs, a model for the evolution offucosyltransferase genes by successive duplications, followed by divergent evolution is proposed, with either two different ancestors, one for the alpha-2/6-fucosyltransferases and one for the alpha-3-fucosyltransferases or a single common ancestor for the two families. The expected properties of such an hypothetical ancestor suggest that the plant or insect alpha-3-fucosyltransferases using chitobiose as acceptor might be the present forms of this ancestor, since fucosyltransferases using chitobiose as acceptor are expected to be of earlier appearance in evolution than enzymes using N -acetyllactosamine. However, an example of convergent evolution of fucosyltransferase genes is suggested for the appearance of the Leaepitopes found in plants and primates.
Abstract. The present knowledge on chemical, enzymatic, serologic and genetic aspects of ABH antigens is reviewed in an effort to produce a simple and coherent genetic model for the biosynthesis of these antigens and chemically related structures. The genetic control of type 1 (Lea, Leb, LeC and Led), type 2 (X, Y, I, and H), type 3 and type 4 ABH and related antigens in different animal and human tissues is analyzed, taking into account the properties of the glycosyltransferases which are involved in their synthesis and considering possible competition for common acceptor and donor substrates. The phylogeny of ABH determinants shows that they appeared as tissular antigens much earlier than as red cell antigens. The ontogeny of ABH antigens suggests that they behave as differentiation antigens, and an effort is made to correlate their tissular distribution in the adult with the embryological origin of each tissue.ABH and related antigens are oligosaccharides. The biosynthesis of oligosaccharide chains implies the participation of several glycosyltransferases, usually one for the addition of each sugar unit. Each enzyme is coded for by different genes which may be located in different areas of the genome. Therefore, the oligosaccharide antigens have a more complex genetic control than polypeptide antigens. The classical concept 'one gene one antigen' cannot by applied to carbohydrate determinants, since their synthesis requires the participation of several enzymes, thus several genes. This multistep biosynthetic process gives some special properties to these antigenic systems.Epistasis: Two or more enzymes, each a product of a different gene, participate in the synthesis of an oligosaccharide epitope. This oligosaccharide structure, made by more than 1 enzyme, can be specifically recognized by a single antibody. This antibody is different from the antibodies that react with the partial or incomplete oligosaccharide epitopes, which are produced if anyone of the glycosyltransferase is not acting (see the Lewis antigens).Each enzyme uses a specific acceptor substrate. However, in certain cases, there is redundancy, that is, more than 1 enzyme can catalyze the transfer of the same sugar unit to the same acceptor (see the X and Le enzymes).In other cases, there is degeneration of the enzyme specificity. That is, a single enzyme can use 2 different receptor substrates and can therefore generate 2 different epitopes (see the Se enzyme). Phylogeny of the ABH AntigensThe sugars of the ABO system are thought of as the main erythrocyte antigens. This concept is correct for the human species. However, animal studies have shown that the ABH antigens appear first as tissular antigens. They are found in ectodermal and endodermal epithelial cells of lower mammals [l] whose red cells are completely devoid of ABH antigens. Furthermore, even in baboons where ABH antigens are expressed on vascular endothelial cells [2], the red cells are negative for ABH. In fact, erythrocytes are the most recent cells to acquire the ABH antigens i...
The three-dimensional structures of fourteen histo-blood groups carbohydrate antigens have been established through a combination of molecular mechanics and conformational searching methods. The conformational space available for each disaccharide, constituents of these determinants, has been throroughly characterized. The results have been organized in a data bank fashion. Larger relatives, i.e. 14 tri- and tetrasaccharides of histo-blood group antigens, have been modelled using a different method for exploring the complex potential energy surface. This approach is aimed at establishing all the possible families of conformations, along with the conformational pathways. Different conformational behaviours are exhibited by these oligosaccharides. Some of them, i.e. Le(x) and Le(y) tri and tetrasaccharides, are very rigid; 99% of their populations belong to the same conformational family. Others, like H type 1, H type 2 or H type 6 oligosaccharides, are essentially rigid, but a secondary conformational family, corresponding to 3-4% of the total population, can arise. Finally, the H types 3 and 4 trisaccharides, and the A type 1 and A type 2 tetrasaccharides are predicted to behave rather flexibly. The information gathered in the present investigation has been used to analyse the body of experimental evidence, either physical or biological, available for this series of carbohydrate antigens. Of special interest are the several different alignments that can be proposed for these molecules. They yield a realistic definition of the three-dimensional features of the epitopes thereby providing essential information about how carbohydrate antigens are recognized by proteins.
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