ABH and Lewis histo-blood group antigens, a model for the meaning of oligosaccharide diversity in the face of a changing world

Abstract

Antigens of the ABH and Lewis histo-blood group family have been known for a long time. Yet their biological meaning is still largely obscure. Based on the available knowledge about the genes involved in their biosynthesis and about their tissue distribution in humans and other mammals, we discuss here the selective forces that may maintain or propagate these oligosaccharide antigens. The ABO, α1,2fucosyltransferase and α1,3fucosyltransferase enzyme families have been generated by gene duplications. Members of these families contribute to biosynthesis of the antigens through epistatic interactions. We suggest that the highly polymorphic genes of each family provide intraspecies diversity that allows coping with diverse and rapidly evolving pathogens. In contrast, the genes of low frequency polymorphism are expected to play roles at the cellular level, although they may be dispensable at the individual level. In addition, some members of these three gene families are expected to be functionally redundant and may either provide a reservoir for additional diversity in the future or become inactivated. We also discuss the role of the ABH and Lewis histo-blood group antigens in pathologies such as cancer and cardiovascular diseases, but argue that it is merely incidental and devoid of evolutionary impact.

Introduction

It has been a century since the ABO groups were discovered by Karl Landsteiner on human red cells and from this work originated the name ‘blood group antigens’. Yet it was soon realized that the same molecules could be present in biological fluids such as saliva and in tissues, most noticeably the gut. Their structure and relationship with other antigens such as the Lewis antigens, which are present in tissues, but only adsorbed on erythrocytes, was then recognized 〚1〛. They have also been found in many animal species, although their presence on red cells is restricted to humans and a few anthropoid apes. For these reasons, the more recently proposed term ‘histo-blood group antigens’ appears appropriate since it emphasizes their tissular nature while keeping the historical blood group aspect which is still so useful in transfusion medicine. Since the early days of serology, much has been learnt about the nature of these antigens, their biosynthesis, their genetics and their tissue distribution in various species. A lot of work has been devoted to understand their biological meaning, but this met with little success as reviewed some years ago 〚2〛. The aim of the present article is to summarize the actual knowledge regarding this family of antigens and to put it in an evolutionary perspective in order to revisit the older hypotheses about their functions.