Evolutionary divergence of the ABO and GBGT1 genes specifying the ABO and FORS blood group systems through chromosomal rearrangements

Fumiichiro Yamamoto

doi:10.1038/s41598-017-09765-2

Abstract

Human alleles at the ABO and GBGT1 genetic loci specify glycosylation polymorphism of ABO and FORS blood group systems, respectively, and their allelic basis has been elucidated. These genes are also present in other species, but presence/absence, as well as functionality/non-functionality are species-dependent. Molecular mechanisms and forces that created this species divergence were unknown. Utilizing genomic information available from GenBank and Ensembl databases, gene order maps were constructed of a chromosomal region surrounding the ABO and GBGT1 genes from a variety of vertebrate species. Both similarities and differences were observed in their chromosomal organization. Interestingly, the ABO and GBGT1 genes were found located at the boundaries of chromosomal fragments that seem to have been inverted/translocated during species evolution. Genetic alterations, such as deletions and duplications, are prevalent at the ends of rearranged chromosomal fragments, which may partially explain the species-dependent divergence of those clinically important glycosyltransferase genes.

Highlights

By GBGT1 gene catalyzes the final step of Forssman antigen biosynthesis
The GBGT1 gene cDNA encoding a functional FS was initially cloned from a dog[18]
Through functional analyses of Forssman-positive mouse and Forssman-negative human FS chimeras and their in vitro amino acid substitution constructs, we have shown that human GBGT1 gene from ordinary individuals contains 2 inactivating amino acid substitutions, Gly230Ser and Gln296Arg, when compared with the functional murine GBGT1 gene[20]

Summary

Introduction

By GBGT1 gene catalyzes the final step of Forssman antigen biosynthesis. Molecular genetic analysis demonstrated that Apae individuals had a dominant-acting functional FS containing the Arg296Gln substitution when compared with that of ordinary non-Apae individuals[6]. There are other species than humans that possess either one or both of the ABO and GBGT1 genes. The ABO genes were investigated of some animal species, including primates[12, 13], mice[14], pigs[15], and rats[16, 17]. In spite of the fact that structural deficiencies of gene-encoded glycosyltransferases have been well elucidated for the ABO and GBGT1 genes, molecular mechanisms/forces causing gene disappearance in some species were unknown. Changes during vertebrate evolution of the chromosomal region encompassing the ABO and GBGT1 genes have been investigated, as well as the regions encompassing other members of the α1–3 Gal(NAc) transferase family genes. I propose the following theory; chromosomal rearrangements have played a significant role in the generation of complex species-dependent gene distribution, by causing duplications and deletions of those glycosyltransferase genes of critical importance in transfusion and transplantation medicines

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Conclusion