Most GT families have significantly expanded in early vertebrates Dropropizine through whole genome duplications, and differential loss or retention of duplicated genes has contributed to the functional divergence of these GT families. GT-23 represents a unique case of an evolutionary ancient GT family that did not diverge during metazoan evolution. We have chosen to study its gene structure as a way to characterize the evolutionary relationships of these genes. Comparative analysis of the fut8 gene in various animal genomes provided few insights into the evolution of this singlecopy gene in metazoans. In contrast with genes encoding a1,3-, a1,3/4- and a1,2-FucTs, all the characterized fut8 genes presented a common poly-exon organization. Metazoan fut8 genes contained a highly variable number of exons, Darifenacin hydrobromide suggesting a complex evolutionary history with many intron gain and loss events. Analysis of the structure and evolution of the fut genes in arthropods showed that the high evolutionary rates found for instance in the coleoptera and diptera branches corresponded to differences in gene organization as well. Intron insertion sites in phase 0 were over-represented in gene sequences encoding the most conserved part of the FUT8 proteins: i4l and i4c in the cysteine-rich domain, and i8l, i9l, i10l and i11l in the catalytic domain. Moreover, in human FUT8 structure, introns i4c and i8c/i9l are located at the C- and N- terminal domain of alpha helix 3 and alpha helix 11 respectively. Such features are proposed to be characteristic of ancient conserved genes. Many exons were shared by different arthropoda orders, such as phtiraptera, coleoptera, hemiptera, diptera, lepidoptera and even crustacea. Remarkably, despite the high conservation of lepidoptera FUT8 sequence with vertebrates and hymenoptera, the exonintron organization of hymenoptera fut8 genes is order-specific with no shared exons. This is particularly surprising because when the analysis is extended to orthologous fut8 genes of other phyla, many Spodoptera intron insertion sites are still conserved throughout the animal kingdom. Particularly, intron positions i7l and i9l are common to most of the fut8 genes analyzed in this work.