The finding of two Dispanin homologs in the brown alga E. siliculosus, which is evolutionary distant to metazoa, and the single Dispanin in the close metazoan relative M.brevicollis are the two only non-metazoan eukaryotic Dispanins. A BLAST search gives that the E. siliculosus proteins have a higher similarity to metazoan family members (best hit E-value,10 210 ) than bacterial Dispanins and M. brevicollis. The M. brevicollis Dispanin share a conserved splice site with all metazoan family members, which suggest that the eukaryotic Dispanins first emerged in a common ancestor of M. brevicollis and the metazoan lineage. Within the metazoan lineage the Dispanins have been lost in at least two separate occasions, i.e. T. adhaerens and in the ecdysozoan lineage (D. melanogaster and C. elegans). The vertebrate Dispanins sort into subfamilies A-D ( Figure 1 ). The DSPA subfamily has six human genes (DSPA1, DSPA2a-d and DSPA3) of which the DSPA2a-c corresponds to IFITM1-3 and DSPA1 to IFITM5. DSPA2d (AC023157) and DSPA3 (AC068580) are two novel identified genes, closely related to the IFITM family. The phylogenetic tree indicates that the DSPA2 genes have undergone an independent duplication in H. Sapiens and M. musculus and these were given a species specific nomenclature, e.g. DSPA2a-d in human. The Dspa4, Dspa5, Dspa6 genes in the phylogenetic tree do not have any clear human orthologs. The DSPB subfamily is only found in tetrapoda and contains three human genes called DSPB1 (TUSC5), DSPB2 (TMEM233) and DSPB3 (PRRT2) whereas Dspb4 is only present in G. gallus. DSPC1 (TMEM90A), DSPC2 (TMEM90B) and DSPC3 (TMEM91) make up the human DSPC subfamily, which is represented in all investigated vertebrates. The DSPD1 (PPRT1) gene is found in all the vertebrate species except the basal organism P. marinus whereas DSPD2 (AL160276) is mammalian specific.