Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc

Peri, Sateesh; Kulkarni, Asmita; Feyertag, Felix; Berninsone, Patricia M; Alvarez-Ponce, David

We expect that animals with a putatively functional CMAH gene should be able to synthesize endogenous Neu5Gc, whereas those with pseudogenic or absent CMAH homologs should not. Given the toxicity of Neu5Gc for humans, determining what animals lack the capability of synthesizing this sialic acid is key from the point of view of human nutrition and xenotransplantation research. Prior studies have quantified Neu5Gc levels in the tissues of many animals. It should be noted, however, that Neu5Gc can be incorporated from the diet (Tangvoranuntakul et al. 2003) , which means that finding Neu5Gc in the tissues of a certain organism does not imply that the organism can synthesize Neu5Gc endogenously. We have produced a list of species that lack a functional CMAH gene, and that should be free from Neu5Gc if fed with a Neu5Gc-free diet. These species are thus interesting candidates for human consumption and/or xenotransplantation. Our list includes, for instance, all poultry, 23 species of fish and the white-tailed deer.