In addition to the abovementioned Cry genes, fishes possess one
more member of CRY (e.g., NP_571862 of D. rerio), which is annotated
as Cry4. The phylogenetic analysis suggests that the Cry4 genes are evolutionarily
older than insect Cry1/2 and vertebrate Cry1/2 (Fig. 2), so that
we hypothesized Cry4 might be a functional intermediate of (6–4)
photolyase and animal CRY. A recently published article indicates that
CRY4 lacks both the nuclear localization signal (NLS)motif and the protein–
protein interaction domain, thus it unlikely manifests circadian
functions (Liu et al., 2015). Overall, our phylogenetic analysis yielded
similar results to the above study; vertebrate Cry consist of three
major groups, Cry1, Cry2 and Cry4 (Fig. 2) (Liu et al., 2015). On the
other hand, our results suggest that animal Cry originated from (6–4)
PHR and Cry4 are evolutionary older than arthropod and vertebrate
Cry1/2.