On the basis of function and sequence similarities, the vertebrate fucosyltransferases can be classified into three groups: alpha-2-, alpha-3-, and alpha-6-fucosyltransferases. Thirty new putative fucosyltransferase genes from invertebrates and bacteria and six conserved peptide motifs have been identified in DNA and protein databanks. Two of these motifs are specific of alpha-3-fucosyltransferases, one is specific of alpha-2-fucosyltransferases, another is specific of alpha-6-fucosyltransferases, and two are shared by both alpha-2- and alpha-6-fucosyltranserases. Based on these data, literature data, and the phylogenetic analysis of the conserved peptide motifs, a model for the evolution offucosyltransferase genes by successive duplications, followed by divergent evolution is proposed, with either two different ancestors, one for the alpha-2/6-fucosyltransferases and one for the alpha-3-fucosyltransferases or a single common ancestor for the two families. The expected properties of such an hypothetical ancestor suggest that the plant or insect alpha-3-fucosyltransferases using chitobiose as acceptor might be the present forms of this ancestor, since fucosyltransferases using chitobiose as acceptor are expected to be of earlier appearance in evolution than enzymes using N -acetyllactosamine. However, an example of convergent evolution of fucosyltransferase genes is suggested for the appearance of the Leaepitopes found in plants and primates.

Cloning and expression of chimpanzee FUT3, FUT5, and FUT6 genes confirmed the hypothesis that the gene duplications at the origin of the present human cluster of genes occurred between: (i) the great mammalian radiation 80 million years ago and (ii) the separation of man and chimpanzee 10 million years ago. The phylogeny of fucosyltransferase genes was completed by the addition of the FUT8 family of ␣(1,6)fucosyltransferase genes, which are the oldest genes of the fucosyltransferase family. By analysis of data banks, a new FUT8 alternative splice expressed in human retina was identified, which allowed mapping the human FUT8 gene to 14q23. The results suggest that the fucosyltransferase genes have evolved by successive duplications, followed by translocations, and divergent evolution from a single ancestral gene.Three human ␣(1,3)fucosyltransferase genes FUT3 1 (1), FUT5 (2) and FUT6 (3) are organized in a cluster, within 1 centimorgan, in the short arm of chromosome 19, in the band 19p13.3 (4, 5).Previous cloning of a bovine ␣(1,3)fucosyltransferase gene (futb) gave a single transcript, and the corresponding cognate enzyme had properties in common with the products of the three human FUT3, FUT5, and FUT6 genes. The position of this futb gene in the phylogenetic tree of fucosyltransferases, showed that the separation of the bovine species from the common evolutionary pathway, during the great mammalian radiation some 80 million years ago, occurred before the duplication events, which originated the present cluster of human FUT3, FUT5, and FUT6 genes and suggested that this bovine enzyme is the orthologous homologue of the ancestor of the FUT3, FUT5, and FUT6 human genes (6).The present cloning and expression of three chimpanzee ␣(1,3)fucosyltransferase genes provides evidence for the existence of at least three distinct, but related ␣(1,3)fucosyltransferase enzymes in this species, each one being the orthologous homologue of one of the human FUT3, FUT5, and FUT6 genes. The position of these chimpanzee genes in the fucosyltransferase phylogenetic tree suggests that the separation of man and chimpanzee from the common evolutionary pathway, about 10 million years ago, has occurred after the duplication events, at the origin of the present cluster of FUT3, FUT5, and FUT6 genes. Addition of the FUT8 gene family to the phylogenetic tree suggests that the appearance of this family preceded the ␣(1,2)-and the ␣(1,3)fucosyltransferase gene families, and the analysis of sequences in GenBank TM /EBI, EST, 2 and UniGene data banks allowed us to map the human FUT8 gene to 14q23. EXPERIMENTAL PROCEDURESCloning-PCR was used to amplify the coding regions and immediately adjacent sequences of FUT3, FUT5, and FUT6 from a chimpanzee, with primers containing extra bases with specific restriction sites, already used for the human genes (7,8). PCR products were digested with EcoRI and XbaI for FUT3, HindIII for FUT6, and HindIII and EcoRI for FUT5. Each gene was cloned between the respective restriction sites of pcDNA1 (Invitrogen). T...

Objective: Definition of the molecular basis of the Reunion and the Bombay red cell and salivary H-deficient phenotypes. Methods: Sequence and expression of FUT1 and FUT2 genes from H-deficient individuals. Family segregation analysis of the mutations responsible for the fucosyltransferase defects of H, secretor and Lewis systems. Results: The Indian red cell H null Bombay phenotype depends on a new mutation of the FUT1 gene. T725 → G changing Leu242 → Arg. Their salivary nonsecretor phenotype is secondary to a complete deletion of the FUT2 gene. The red cell H weak Reunion phenotype depends on another new mutation of FUT1, C349 → T which induces a change of His117 → Tyr. Their salivary nonsecretor phenotype is due to the known Caucasian inactivating mutation G428 → A. Conclusion: Single prevalent FUT1 and FUT2 point mutations and a deletion are responsible for the Indian Bombay H null and the Reunion H weak phenotypes found on Reunion island. This is in contrast with other H-deficient phenotypes where sporadic nonprevalent inactivating mutations are the rule.