The IFITM gene family was divided into three clades. Clade I was further divided into several sub-clades. To test whether there is functional divergence between different clades or between different sub-clades, we estimated type I divergence using DI-VERGE v2.0 [32] and detected significant functional divergence between IR-IFITM and IFITM5, and between IFITM10 and IFITM5 (P,0.01). However, functional divergence signal was not detected between the IR-IFITM genes and IFITM10 (P = 0.0655) ( Fig. 5 and Table 2 ). IFITM10 genes are divided into two subgroups, terrestrial-type and aquatic-type and significant functional divergence was also detected between the two sub-groups (Fig. 5D ). Among IR-IFITM genes, although IFITM2 and IFITM3 might originate from IFITM1 via gene duplication, there is no functional divergence observed between IFITM1 and IFITM2&3 genes (data not shown).