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

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 o n the available knowledge about the genes involved in their biosynthesis. a nd about their tissue distribution in humans and other mammals, we discuss here the selective forces that may maintain or propagate these oligosacchar ide antigens. The ABO, alpha1,2fucosyltransferase and alpha1,3fucosyltransf erase 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 ar e expected to play roles at the cellular level, although they may be dispen sable at the individual level. In addition, some members of these three gen e 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. (C) 2001 Societe fr ancaise de biochimie et biologie moleculaire / Editions scientifiques et me dicales Elsevier SAS. All rights reserved.