IFITM family contains seven members (IFITM1, IFITM2, IFITM3, IFITM5, IFITM6, IFITM7 and IFITM10), as well as some IFITM-like genes. All vertebrate IFITM genes are divided into three clades ( Fig. 2A) , implying origins from three progenitors. Clades I, II and III contain IR-IFITM, IFITM5 and IFITM10 genes, respectively. Substantial functional divergences occurred between IR-IFITM, IFITM5 and IFITM10 genes, indicating that IR-IFITM, IFITM5 and IFITM10 experienced individual evolutions. IR-IFITM, IFITM5 and IFITM10 genes are usually located in two loci (Fig. 4) . One locus contains only the IFITM10 gene, and the other locus contains various numbers of IR-IFITM genes with a syntenic location with IFITM5, forming an IFITM genecluster. The two loci can be used as good markers to trace the evolutionary history of IFITM family. They are located in two different chromosomes in lower aquatic vertebrates, and evolved to lie in one chromosome by chromosomal fusion in higher mammals (Fig. 4A) . The syntenic relationship of IR-IFITM genes and the presence of more IR-IFITM genes in mammals than other vertebrates suggest that IR-IFITM gene sub-family experienced a rapid expansion via tandem duplication during evolution from lower vertebrates to mammals.