The evolutionary history of sialylation - Perspectives from fish genomes

Abstract

Sialic acids are key determinants of carbohydrate structures that play important roles in a variety of biological functions. In order to obtain a better understanding how sialylation developed during evolution we investigated two completely sequenced teleost genomes (Takifugu rubripes and Danio rerio) with emphasis on the proteins involved in biosynthesis and recognition of sialic acids. The analysis revealed the existence of all key enzymes crucial for sialic acid metabolism including putative orthologues for almost all 20 sialyltransferases (STs) known for mammalian species. A thorough phylogenetic analysis of all ST sequences has provided strong evidence that the development of the major ST branches occurred well before the diversification into protostomes and deuterostomes strongly suggesting that the defining characteristics of STs have not changed much in 1000 million years. Interestingly, from the relationship between the ST subfamilies it can be deduced that the evolution of the different ST lineages was driven by the availability of appropriate acceptor substrates.In contrast to STs, the largest family of sialic acid-recognizing lectins found in mammals, the siglecs, seems to be a relatively new invention in evolution. Analysis of the two teleost genomes revealed only one unambiguous orthologue of the known mammalian siglecs showing highest sequence similarity to mammalian Siglec-4, the myelin-associated glycoprotein (MAG). Although the low sequence similarity in the cytoplasmic tail, different splice variants and the existence of several motifs implicated in signal transduction suggest alternative biological functions for this part of the protein, the high conservation of genomic organization, binding specificity and expression of Siglec-4 from fish to mammals emphasizes an indispensable role for this protein in all vertebrates in contrast to other Siglecs which maintained a high degree of structural and possibly functional flexibility during evolution.