During the course of metazoan evolution the Dispanins have expanded and diverged into four distinct subfamilies. However, it has also been lost in the basal metazoa T. adhaerens and the ecdysozoan lineage, which show that it is not essential for all metazoan life. Although we were unable to create a stable phylogenetic tree that include both vertebrate and invertebrate sequences BLAST searches suggest that the DSPC and D subfamilies are the oldest of the vertebrate subfamilies as the invertebrate sequences has higher resemblance to these two subfamilies ( Figure 2) . Moreover, the DSPC and D subfamilies forms a separate cluster from DSPA-B (Figure 1) . Hence, the phylogenetic analysis suggests that the DSPA and B subfamilies have their origin close to the radiation of teleost, although DSPB have been lost in D. rerio (Figure 1 and 4) . The DSPC family is found in two to three copies in all vertebrates and is the most widespread family as the BLAST classification suggest that it is present in two invertebrate species and E. siliculosus. In mouse, the family members are expressed predominantly in brain tissues (Dspc1/Tmem90a, Dspc2/Tmem90b) or ubiquitously (Dspc3/ Tmem91). DSPC1 (TMEM90A) has been proposed to have a role in striatial functioning and the pathophysiology of Huntington's disease and is localized to the Golgi apparatus [16] . The DSPD family has been lost at several occasions, both in vertebrates and invertebrates ( Figure 2 ). The mouse Dspd1 (Prrt1) gene is ubiquitously expressed with the highest expression in B-cells according to BioGPS [17] . However, no previous studies have been performed on the DSPD subfamily. The DSPB subfamily is found in tetrapoda and has three members in human and mouse. Mice expression profiles from BioGPS shows that Dspb3 (Prrt2) is exclusively expressed in brain tissues and that Dspb1 (Tusc5) is expressed in dorsal root ganglia and adipose tissues. In agreement with this expression data, Dspb1 (Tusc5) has been suggested to be involved in neural regulation of adipocyte differentiation and is regulated by PPARc [18, 19] . The DSPA/IFITM subfamily is the most numerous and the mouse and human genes are all clustered in a consecutive manner on chromosome six and eleven, respectively. These regions share a conserved synteny (http:// cinteny.cchmc.org/) and are flanked by the ATHL1 and B4GALNT4 genes on each side, which is strong evidence for the genes to have their origin in common evolutionary gene duplications. This is supported by the phylogenetic analysis ( Figure 1 ) for DSPA1 (IFITM5) and DSPA3 (AC068580), which have orthologs in all tetrapoda. However, for the DSPA2 group (DSPA2A-D/IFITM1-3 and AC068580) the phylogeny suggests that M. musculus and H. sapiens have undergone independent expansions of the group. Rather than being created by independent gene duplications in the two species, it is possible that these genes are subject to concerted evolution, where paralogous genes within a species are more conserved towards each other than towards orthologs in other species. This phenomenon is most common in tandemly repeated genes, such as the DSPA2 group, and is believed to primarily be the result of recombination mechanisms [20] . Interestingly, also the Dspa4a-f genes of X. tropicalis seem to have undergone and independent expansion. However, the phylogeny is not strong enough to prove that the Dspa4a-f genes are orthologous to the mammalian DSPA2 genes (Figure 1 ). The DSPA/IFITM subfamily is the most well studied and is a multifunctional family of which its antiviral properties are best understood [8] . The family is expressed in many mouse tissues with the highest expression in mast cells, macrophages and osteoblasts according to BioGPS. We add two novel human members to this subfamily: DSPA2D, which is closely related to DSPA2C (IFITM3) and DSPA3, which forms a distinct cluster (Figure 1 ). Both these genes are poorly characterized. Microarray data from Array Express (www.ebi.ac.uk/ arrayexpress/) shows that DSPA3 is upregulated by interferon after exposure of macrophages to interferon-gamma in a study (E-GEOD-5099) where DSPA2a-c (IFITM1-3) also were induced [21] . The mouse Dspa3 gene is like the other genes of this subfamily situated on chromosome seven, but is 1.5 Mbp away from the DSPA (IFITM) cluster where the other genes reside. Hence, Dspa3 could explain the mild phenotypes and be responsible for the suggested functional redundancy that was found when deleting the whole DSPA (IFITM) loci [22] .