Is there a universal glycan alphabet

Abstract The fact that the sizes of DNA and protein alphabets are 4 and 20 became textbook material a few decades ago. In contrast, several monosaccharides are known to constitute naturally occurring glycans but it is not clear if they constitute a universal set. Pathways for the biosynthesis of 55 monosaccharides have been delineated from a variety of organisms. We exploited this set of experimentally characterized sequences to search for their homologs in nearly 13,000 prokaryotic genomes. Our results indicate that the usage of monosaccharides is not conserved across prokaryotes, unlike those of nucleic acids and proteins. Substantial variations exist in the set of monosaccharides within phyla and genera; in fact, marked variations are found even among different strains of a species. Based on prevalence, these monosaccharides are classified into Extensive, Intermediate and Rare group. A limited set of enzymes suffice to biosynthesize the Extensive group of monosaccharides and it appears that these monosaccharides originated before the formation of the three domains of life. In contrast, Rare group monosaccharides are confined to a few species in a few phyla, suggesting that they have evolved much later in the course of evolution. Endosymbionts and mollicutes have lost these pathways altogether, as a consequence of host dependence and lack of cell wall, respectively. These variations beget questions concerning the contribution of different sets of monosaccharides to an organism’s fitness.