That many birds migrate over long distances is a well-known fact. But reading the book "World on the Wing: The Global Odyssey of Migratory Birds" by Scott Weidensaul proved to be a true eye-opener. I also learned a fact that really stuck with me. When flying for remarkably long distances, often many thousands of kilometers over open oceans, birds sense the Earth's magnetic field to help orient themselves. They accomplish this through the effect of light on proteins called cryptochromes. Not having heard of these proteins before I was intrigued. How can they enable magnetic perception?
In many plants and animals, some types of cryptochromes function as blue-light-sensitive photoreceptors. As such, they are important for circadian rhythm regulation in Arabidopsis thaliana and the fruit fly Drosophila melanogaster. But cryptochromes are members of a large and very widely distributed protein family whose members have different functions. Most strikingly, cryptochromes share extensive sequence similarity with photolyases, proteins that contain the cofactor flavin adenine dinucleotide (FAD) and repair DNA damage induced by "far UV" light (wavelengths <300 nM). The predominant form of UV damage on DNA is the formation of "cyclobutyl pyrimidine dimers" (CPDs) at adjacent pyrimidines (Figure 1). Upon excitation by "near UV"/blue light (wavelengths 300-450 nM) the photolyase-FAD enzyme transfers the electrons that are needed to split the pyrimidine dimers and repair UV-damaged DNA. This is known as photoreactivation, an evolutionarily ancient mechanism that probably arose in early Earth before the formation of the ozone layer. It's an efficient way to reverse the damage of UV-light with the aid of blue light. Photoreactivation is a conserved mechanism in many organisms, from bacteria to plants, fungi, and animals. But humans and other placental mammals have lost it and replaced it with the less efficient nucleotide excision repair.
Photolyases and cryptochromes are evolutionarily related but can be subdivided into several subfamilies based on the extent of their sequence similarity. They also differ in the distribution of domains within the protein, domains that turn out to be very important for their function (Figure 2). They all possess a photolyase-related region and a domain involved in binding FAD, but photolyases lack a variable C-terminal domain found in cryptochromes. In addition, there is a group of proteins whose sequences place them phylogenetically "in between" photolyases and cryptochromes. These proteins are called Cry-DASH and have diverse functions in organisms ranging from archaea to vertebrates. Like photolyases, CRY-DASHs are involved in repair of DNA, but they target single-stranded rather than double-stranded DNA. Like cryptochromes, CRY-DASHs can function as photoreceptors in organisms such as fungi and in the cyanobacterium Synechocystis. This in between group thus seems to provide the missing link between the evolution of repair and regulatory functions.
How photolyases and cryptochromes evolved to carry out their different light-dependent functions is unclear. As mentioned before, their capacity to sense blue light is a feature that likely evolved very early in Earth's history. Thus, plant and animal cryptochromes probably evolved from some ancestral photolyases. One of the most fascinating adaptations is, undoubtedly, the involvement of cryptochromes in bird navigation. Numerous species, some of them tiny songbirds, travel non-stop for thousands of miles using celestial cues and the Earth's magnetic fields to skillfully navigate the skies. How these animals complete these journeys is still not fully understood, but the current proposal involves cryptochromes in the birds' eyes (Figure 3). When activated by blue light an electron-transfer reaction occurs between the FAD co-factor and several tryptophan residues located nearby within the cryptochrome. This reaction generates radical pairs with quantum effects (yes, this involves quantum mechanics!) that can sense the Earth's weak magnetic fields. In a way, it appears that bird's eyes can "see" magnetic fields, giving a completely new meaning to the phrase "from a bird's eye view." This may sound bizarre and immensely complex, but it is currently the preferred explanation. And this exquisite biological function is tied to and derived from those ancestral microbes that used blue light to repair DNA damage. But in birds this astonishing adaptation provides them with the enviable capacity to find their way around the globe, free of compasses or GPS, using cues that we humans simply can't perceive.