The glycan alphabet is not universal: a hypothesis.

Several monosaccharides constitute naturally occurring glycans, but it is uncertain whether they constitute a universal set like the alphabets of proteins and DNA. Based on the available experimental observations, it is hypothesized herein that the glycan alphabet is not universal. Data on the presence/absence of pathways for the biosynthesis of 55 monosaccharides in 12 939 completely sequenced archaeal and bacterial genomes are presented in support of this hypothesis. Pathways were identified by searching for homologues of biosynthesis pathway enzymes. Substantial variations were observed in the set of monosaccharides used by organisms belonging to the same phylum, genera and even species. Monosaccharides were grouped as common, less common and rare based on their prevalence in Archaea and Bacteria. It was observed that fewer enzymes are sufficient to biosynthesize monosaccharides in the common group. It appears that the common group originated before the formation of the three domains of life. In contrast, the rare group is confined to a few species in a few phyla, suggesting that these monosaccharides evolved much later. Fold conservation, as observed in aminotransferases and SDR (short-chain dehydrogenase reductase) superfamily members involved in monosaccharide biosynthesis, suggests neo- and sub-functionalization of genes led to the formation of the rare group monosaccharides. The non-universality of the glycan alphabet begets questions about the role of different monosaccharides in determining an organism's fitness.