Birds that migrate over long distances, exactly how to navigate and locate the biological "sense of direction" to fight the eyes or hide the secret of the "key" and "hand in hand" competitors

The author | Han raised an eyebrow

Arctic terns travel 40,000 kilometers a year to the North and South Poles, Coco Xili Tibetan antelope thousands of kilometers of great migration, black-veined golden-spotted butterflies four generations of relays to and from the North American continent... In nature, many organisms seem to be able to complete amazing long-distance migration without the help of foreign objects, how exactly do they navigate and locate?

Recently, an international team composed of Xie Can, a researcher at the Hefei Institute of Physical Sciences of the Chinese Academy of Sciences, and Hall, a professor at Oxford University in the United Kingdom, and Morliterson, a professor at Oldenburg University in Germany, found that the cryptochrome 4 protein of migratory birds is more sensitive to magnetic fields than in non-migratory birds, revealing the magnetic induction mechanism mediated by this protein. The research results were published in Nature on June 23 in the form of a cover article.

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For decades, scientists have been searching for where the "compass" in animals comes from. As evidence of the ability of migratory birds to perceive geomagnetic fields has been found, scientists have gradually paid attention to the fact that "organisms can sense geomagnetic fields" and tried to decipher the mechanism by which organisms perceive magnetic fields.

This biological "magnetic induction" has also been described as a "sixth sense". "The field of biomagnetic induction has been moving forward in doubt and hope from the beginning." Xie Can sighed.

From the 1960s and 1970s, the concept of migratory animals being able to sense the geomagnetic field was widely accepted by the academic community, and it was not until 2000 that scientists discovered that cryptochrome Cryptochrome is likely to be a key molecule in the magnetic navigation process of birds. Later, cryptochrome proteins have been considered "sole candidates" for magnetoporeptor proteins.

Cryptochrome protein is a protein that is sensitive to blue light. It plays an important role in regulating the circadian clock and inducing magnetic field by forming free radical electrons with flavin adenine dinucleotides (FAD). FAD is actually vitamin B2 – a redox coenzyme. It absorbs blue light and is reduced, snatching electrons from neighboring tryptophan, which is called "electron transfer", where unpaired electrons form free radical pairs.

In 2015, Xie Can's team first reported a new magnetic receptor protein MagR in Nature materials, providing a second "candidate" for unraveling the mystery of the "sixth sense" magnetism.

Xie Can said bluntly that the current animal magnetic induction mechanism is still an unsolved mystery, and there is no model that can be widely accepted by the entire field, whether it is cryptochrome protein or MagR protein, which are in dispute.

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It was the discovery of the MagR protein that led to Xie Can's collaboration with international teams such as Hall and Morritson, who have long been engaged in research in the field of biomagnetic induction.

"We wanted to experimentally test the hypothesis of free radical-to-magnetic induction, which is to test the magnetic field effect of cryptochrome proteins, and protein samples are the cornerstone of testing. Recombinant proteins are expressed and purified and are essential. Xu Jingjing, Morlitson's doctoral student and first author of the paper, told China Science News.

Excitingly, Xie's team has a unique protein expression purification system and extensive experience in magnetically sensing proteins, which can effectively purify and prepare a large number of cryptocyanin proteins that fold correctly and bind TO auxiliary groups.

"It can be said that FAD is the 'heart' of the magnetically sensitive cryptochrome protein." Xu Jingjing said that cryptochrome protein samples that bind to FAD are biologically active.

Morritson said: "The large preparation of a large number of bird cryptophanter pigment proteins that bind to FAD is a major achievement and a key first step in this study. ”

In the previous collaboration, cryptochrome and magnetic receptor proteins prepared by Xie Can's laboratory crossed the ocean to the Hall laboratory at Oxford University, but the researchers found that the protein activity of these proteins was greatly reduced during long-distance transportation and freeze-thaw.

In order to solve this problem, in November 2016, Xu Jingjing came to Xie Can's research group and conducted two months of scientific training on protein purification.

After half a year of experimentation and optimization, Xu Jingjing built a stable and efficient protein expression and purification platform, and for the first time prepared a large number of cryptochrome 4 proteins for several different birds, including the European robin that migrated at night. For more than two years after that, xu Jingjing prepared a cryptochrome protein sample in the Morritsen laboratory in Germany, and then flew to Oxford University in the United Kingdom with the sample on the same day to carry out intense experiments.

Studies have shown the presence of cryptochrome proteins in the retinas of birds, and collaborators studied the prepared protein samples using multiple magnetic resonances and new spectroscopic techniques in the Oxford laboratory, demonstrating that it is highly sensitive to magnetic fields.

"Electron transfer of cryptochrome proteins after being excited by blue light is crucial in the magnetic induction process." Morritson explains. Protein molecules consist of a chain of amino acids. Cryptochrome 4 has 527 amino acids, of which 4 tryptophans are particularly important for magnetism. Calculations in quantum mechanics suggest that electrons may be transferred from one tryptophan to the next, creating a pair of magnetically sensitive free radicals.

Experimental tests have also confirmed that these four tryptophan-consisting electron transport chains, and that the resulting free radicals are essential to explain the observed magnetic field effects.

This also means that the researchers experimentally validated the free radical pair hypothesis with cryptochrome proteins from migratory birds.

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However, the researchers admit that this does not confirm exactly what cryptochrome 4 is the magnetoreceptive molecule they are looking for, because in this study, the researchers tested individual proteins in vitro and the magnetic field used in the experiment was stronger than the geomagnetic field.

"But these results are important because they show for the first time that a protein molecule in the visual organs of migratory birds is sensitive to magnetic fields." But whether magnetic induction really occurs in the eyes of birds needs to be further confirmed, but it is not yet technically possible. Morritson said.

The researchers also believe that these proteins should be more magnetically sensitive in their natural environment. In addition, other proteins that bind to cryptochrome may also amplify magnetic sensitivity through a mechanism that makes it possible for birds to detect weak geomagnetic fields.

"We are very open to looking for other proteins that may be involved in this complex process, and we cannot easily rule out any possible interaction proteins and possible magnetic induction mechanisms." Xie Can said.

In fact, Morritson had been skeptical of the MagR protein discovered by Xie Can's team, and even wrote a long article to refute it, but it did not affect their cooperation with each other in the slightest.

Xie Can told China Science Daily, "Even in this study, the three of us often have differences of academic views, but our goal is the same, that is, to gradually uncover the mysterious mechanism of animal magnetic induction and biological navigation through rigorous experiments." ”

In Xie Can's view, the clarification of magnetic induction and biological navigation principles may lead to the proposal of new models of physics, the discovery of new mechanisms of biology, and even promote the development of a new generation of bionic navigators and locators, as well as biomagnetic technology.

"The mechanism of magnetic induction and biological navigation is not yet clear, and I will continue to cooperate with Morritson and Hall for a long time, and we look forward to more scientists from different research backgrounds to join." Xie Can said.

Related thesis information: https://doi.org/10.1038/s41586-021-03618-9