Cryptochromes are receptors for blue and ultraviolet (UV-A) light that share sequence similarity to DNA photolyases, DNA-repair enzymes that use blue light to repair UV-induced DNA damage by removing pyrimidine dimers from DNA [1
]; cryptochromes have no photolyase activity, however [1
]. There are two types of DNA photolyase, which repair different types of damage: CPD photolyases repair cyclobutane pyrimidine dimers (CPDs), and 6-4 photolyases repair 6-4 pyrimidine pyrimidone photoproducts. These photolyases together with the cryptochromes make up the photolyase/cryptochrome superfamily [5
]. According to their sequence similarities, cryptochromes from a range of organisms can be clustered, more or less, into three subfamilies (Figure ): plant cryptochromes, animal cryptochromes and cryptochrome-DASH proteins (CRY-DASH; see below).
An unrooted phylogenetic tree of the photolyase/cryptochrome superfamily, with subfamilies indicated on the right. Abbreviations: A, archaea; B, bacteria; F, fungi I; insects; P, plants; S, sponges; V, vertebrates.
Cryptochromes are widely distributed in bacteria and eukaryotes but are not found in archaea, although archaea do have a CPD photolyase (see Figure ). The first cryptochrome gene to be identified was Arabidopsis CRY1
], and cryptochromes were soon found by homology in other plant species and in animals. Soon after the cloning of the first 6-4 photolyase from Drosophila
], a related sequence was discovered in the human expressed sequence tag (EST) databases that proved to encode human cryptochrome 1 (hCry1) [8
]. Cryptochromes have now been found in various animal lineages, including insects, fish, amphibians, and mammals. Animal cryptochromes act as components of the circadian clock that control daily physiological and behavioral rhythms and as photoreceptors that mediate entrainment of the circadian clock to light [3
It was initially thought that only higher eukaryotes had cryptochromes and that prokaryotes had photolyases but not cryptochromes, but further searches of the more recently available genome databases revealed the presence of a cryptochrome gene in cyanobacteria (Synechocystis
]. This new type of cryptochrome was referred to as CRY-DASH, to underscore its relationship with cryptochromes found in Drosophila
, and Homo
(although CRY-DASH itself is not found in Drosophila
or humans) [11
]. CRY-DASH proteins have been found not only in the photosynthetic cyanobacteria but also in non-photosynthetic bacteria, fungi, plants and animals, including Arabidopsis
, zebrafish, and Xenopus
(see Figure ). The biological function of CRY-DASH proteins remains unknown at present.
The phylogenetic tree shown in Figure illustrates the evolutionary relationships of photolyases and cryptochromes from different organisms. According to the tree topology, the photolyase/cryptochrome superfamily contains four subfamilies: animal cryptochromes/6-4 photolyase, plant cryptochromes, CRY-DASH proteins, and CPD photolyases. It is intriguing that animal cryptochromes and 6-4 photolyases are clustered together into the same clade, suggesting a close evolutionarily relationship between them even though they perform very different functions.