Animal magnetic sense explained by tiny protein 'compasses'

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This is so cool.

When it was first proposed, the notion that animals can detect the Earth’s magnetic field was ridiculed, but we now know that everything from birds and whales to butterflies, worms, and wolves know instinctively where north is thanks to an innate magnetic sense. How else are dogs supposed to find their preferred north-south pooping axis?

What scientists couldn’t figure out was how they do it. Now, for the first time, a team in China has identified tiny clumps of protein that appear to align themselves with Earth’s geomagnetic field lines like a compass, and it’s thought that they can influence the nervous system to help animals navigate their surroundings. 

Until now, the two most popular hypotheses used to explain animal magnetic sense were cryptochromes - proteins that respond to magnetic fields and are thought to play a role in maintaining the circadian rhythms of plants and animals - and iron-binding magnetite crystals, which are found in various organs and become magnetised when exposed to a magnetic field. 

While promising, neither option was convincing enough on its own to fully explain the phenomenon, and scientists couldn’t figure out how the two could possibly be linked. So a team from Peking University decided to investigate cryptochromes in the fruit fly genome to see if there was something they were missing. 

Sure enough, they identified an iron-binding protein called MagR, which forms rod-like clumps with cryptochromes. It’s thought that this MagR-cryptochrome cluster functions like a compass, responding to changes in the magnetic field and signalling nearby cells, which in turn prompt the nervous system to give the body cues about its whereabouts.

"The nanoscale biocompass has the tendency to align itself along geomagnetic field lines and to obtain navigation cues from a geomagnetic field," lead researcher Can Xie told Ian Sample at The Guardian. "We propose that any disturbance in this alignment may be captured by connected cellular machinery, which would channel information to the downstream neural system, forming the animal’s magnetic sense."

These protein clusters aren’t just found in fruit flies - the team found them in pigeons and monarch butterflies too, and when isolated, they behaved really, really strangely. "In the lab, the proteins snapped into alignment in response to a magnetic field. They were so strongly magnetic that they flew up and stuck to the researchers’ tools, which contained iron. So the team had to use custom tools made of plastic," New Scientist reports.

Interestingly, further research found that these protein structures can also form in mole rat, minke whale, and even human cells, which offers up the possibility that we could have the same innate magnetic sense of other animals, but perhaps we’re just not as attuned to it as they are. 

"Human sense of direction is complicated," Xie told The Guardian. "However, I believe that magnetic sense plays a key role in explaining why some people have a good sense of direction."

It's still just a hypothesis - Xie and his team are yet to figure out exactly how the clusters communicate with other parts of the body to influence an animal's behaviour, but it's the best hypothesis we've got so far. The next step will be to observe how animals behave when the gene that codes for MagR is removed, which will prove if these clusters are indeed involved in the mechanism. If they are, and we can observe them working in humans, it's going to be mind-blowing.

The study has been published in Nature Materials.

ORIGINAL: Science Alert

BEC CREW

17 NOV 2015

One cell is all you need

ORIGINAL: News Harvard

By Peter Reuell. Harvard Staff Writer

January 4, 2013

Innovative technique can sequence entire genome from single cell

Rose Lincoln/Harvard Staff Photographer. Mallinckrodt Professor of Chemistry and Chemical Biology Xiaoliang Sunney Xie (from left) has co-authored a paper on gene sequencing with graduate student Alec Chapman and postdoctoral fellow Chenghang Zong. The paper demonstrates a new method for DNA amplification that could signal a breakthrough in genomics.

The notion that police can identify a suspect based on the tiniest drop of blood or trace of tissue has long been a staple of TV dramas, but scientists at Harvard have taken the idea a step further. Using just a single human cell, they can reproduce an individual’s entire genome.

As described in a Dec. 21 paper in Science, a team of researchers, led byXiaoliang Sunney Xie, the Mallinckrodt Professor of Chemistry and Chemical Biology, and made up of postdoctoral fellow Chenghang Zong, graduate student Alec Chapman, and former graduate student Sijia Lu, developed a method — dubbed MALBAC, short for Multiple Annealing and Looping-based Amplification Cycles — that requires just one cell to reproduce an entire DNA molecule.

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More than three years in the making, the breakthrough technique offers the potential for early cancer treatment by allowing doctors to obtain a genetic “fingerprint” of a person’s cancer from circulating tumor cells. It also could lead to safer prenatal testing for a host of genetic diseases.

“If you give us a single human cell, we report to you 93 percent of the genome that contains three billion base pairs, and if there is a single base mutation, we can identify it with 70 percent detectability, with no false positives detected,” Xie said. “This is a major development.”

In a second paper, published simultaneously, researchers from Xie’s lab worked with scientists at Peking University in China to demonstrate MALBAC by sequencing 99 sperm cells from one individual and examining the paternal and maternal contribution to each cell’s genome.

As its name suggests, Xie said, MALBAC is a type of DNA amplification that allows researchers to duplicate the single DNA molecule present in a cell many times so it can be analyzed in the lab.

“While other methods of DNA amplification exist, most — like polymerase chain reaction (PCR) or multiple displacement amplification (MDA) — suffer from a specific problem,” Xie said. “Because they amplify exponentially, both have bias. They dramatically amplify some parts of the genome, but amplify others very little.”

By comparison, he said, MALBAC relies on linear amplification, meaning it is able to minimize the sequence-dependent bias.

Just as it does with other methods, the amplification process begins by splitting the DNA double helix into two single strands. Xie’s team then adds a random “primer” — tiny fragments of DNA — that binds in dozens of locations along each strand.

To extend those primers, Xie’s team used a DNA polymerase, the same cellular “machine” that synthesizes DNA as cells divide. Using that machine, researchers are able to extend the primers from as few as seven bases to as many as 2,000. Upon heating, they break the elongated primers apart from the original DNA, yielding half products.

When those half products are then amplified using the same primers, the two ends of the DNA combine, forming a loop that prevents it from being amplified again. The leftover half products and the original DNA are subject to another cycle of amplification. After five cycles of such linear pre-amplification, the full product is amplified by PCR to produce enough material for sequencing.

Despite the high coverage, DNA polymerases do occasionally make errors, Xie explained. To ensure that the genome produced by MALBAC is accurate, researchers turned to a different technique.

“Many diseases are associated with a single base mutation,” Xie said. “The challenge, however, is that finding one mutation in more than 3 billion base pairs is like looking for a needle in a haystack. Earlier techniques, like PCR or MDA, start with many cells, making the challenge even greater; a single mutation simply gets lost in the process. MALBAC, however, starts with a single cell, so it is easier to identify those mutations when they happen.”

To ensure MALBAC’s accuracy, Xie’s team simply let the original cell divide.

While the polymerase that researchers use to build the DNA sequence is highly accurate, only making one mistake per 10,000 bases, letting the cell divide gives researchers a chance to double check its work.

“The chances of the same mistake being made at the same base position are about one in 100 million,” Xie said. “If we let the cells divide again, and sequence three cells, the chances go up to one in 10 billion, less than the number of bases in the entire DNA molecule, so we can remove all the false positives.

“Getting that level of accuracy is very important, because if a doctor tells a patient that he detects a mutation, he doesn’t want to be wrong,” he continued. “When we use MALBAC, if a mutation appears in two or three related cells, we know it must be a real mutation.”

As a demonstration of MALBAC’s power, Xie and his team monitored the mutations that arose in a single cancer cell as it divided over 20 generations, and uncovered as many as 50 newly acquired mutations.

“This is the first time the mutation rate of a human cell has been measured directly,” Xie said. “Because we can now see the unique, newly acquired bases, we can study the dynamics of the genome in a way that was not possible before.”

Tsunami-fearing city looks to animals for warning signs

ORIGINAL: ASAHI AJW

By SHOJI NOMURA/ ASAHI SHIMBUN WEEKLY AERA

May 01, 2012

Naoyuki Yada, associate professor at the Kanagawa Institute of Technology, monitors cats for warning signs of a large earthquake in Atsugi, Kanagawa Prefecture. (Yuki Yamamoto)

SUSAKI, Kochi Prefecture--Feeling vulnerable to a catastrophe, this coastal city on the island of Shikoku will monitor fish, chickens and other animals for signs of a huge earthquake that could spawn a monster tsunami.

The Susaki city government is following the long-held idea that animals can sense impending disaster. The city said April 5 that it will release details of the monitoring of the animals to the public, but it will not issue evacuation orders based only on their behavior.

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Susaki city hall

The city’s decision to regularly monitor animal behavior for possible earthquakes came after the central government released its disaster forecast in March.

According to the forecast, Susaki could be hit by a tsunami as high as 23.9 meters if a powerful earthquake strikes with its epicenter around the Nankai Trough, which runs just off the island. The city, with a population of about 25,000, is prepared for only a 7-meter-high tsunami.

(Records showed that such earthquakes have struck the region in 1707, 1854 and 1946.)

After the Great East Japan Earthquake rocked the Tohoku region on March 11 last year, a 3.2-meter-tall tsunami hit Susaki, the highest in western Japan.

The city’s planned animal-monitoring project was announced after a researcher of structural geology who surveyed Shikoku suggested the step at a meeting of the city’s disaster task force in early April.

“I believe we should not dismiss such a measure even if it has not been scientifically proved to be associated with earthquakes,” said Yoshihito Myojin, the deputy mayor who heads the task force. “We are going to flesh out details of the project to minimize the deaths from tsunami to close to zero.”

The monitoring also involves checking underground water levels.

For centuries in Japan, strange animal behavior and other unusual occurrences have been reported before major earthquakes. They are known as macroscopic anomalous phenomena.

Well-known examples include catfish swimming erratically, rats running wild and wells drying up.

Catfish's activities are recorded with an infrared ray sensor. (Yuki Yamamoto)

China is a frontrunner in research intended to establish links between animal behavior and seismic activity, mainly at the Chinese Academy of Sciences, the nation’s top research center, and a wild animal zoo at Peking University in Beijing.

But reports about unusual animal behavior and events have never drawn serious attention from Japanese scientists. They say such incidents constantly occur, regardless of an earthquake.

That perception changed somewhat after the magnitude-7.3 Great Hanshin Earthquake struck the Kobe area on Jan. 17, 1995, killing more than 6,000 people.

After that temblor, numerous reports were provided by people who said they witnessed precursors of the quake.

A book titled “Zencho Shogen 1,519!” (Testimonies of precursors 1,519) authored by Kiyoshi Wadatsumi, professor emeritus at Osaka City University and a geologist, was published in September 1995, carrying about 3,000 such anecdotes. Among them are 1,519 cases reported by citizens in response to Wadatsumi’s request made through the media.

Reports related to living creatures totaled 781--324 about mammals, 281 about birds, 93 about fish, 40 about reptiles and 43 about insects.

The first accounts occurred about a month before the quake and the number peaked on Jan. 16, according to the book.

The episodes include:

• a normally quiet dog barking three hours before the temblor and digging a hole under a fence in the garden to escape (a resident in Kobe’s Nishi Ward); 
• two pet frogs kept indoors emerging from hibernation and making croaking sounds three days before the quake (a resident in Osaka’s Higashi-Yodogawa Ward); 
• 10 eggs that were laid on Jan. 12 and bought at a supermarket, each containing two yolks (a resident in Osaka’s Higashinari Ward); 
• hundreds of mullets measuring about 30 centimeters each swimming up the Akashi river in Hyogo Prefecture on Jan. 15 (a resident in Akashi, Hyogo Prefecture).

The Susaki municipal government is not the only local government in Japan looking at animals for warning signs.

Shizuoka Prefecture began a similar project in 1996, soliciting information from the public through its website. Prefectural officials have yet to decide if they will use the data for disaster countermeasures.

The central government said there is an 88-percent likelihood that a Tokai earthquake, expected off the prefecture and the surrounding area, will strike within the next 30 years.

Some researchers speculate that animals behave differently before disasters because they can detect rising ion levels and changes in electromagnetic waves in the atmosphere that result from tectonic activities. Or they may be able to sense changes in electric currents running deep inside the Earth.

Although macroscopic anomalous phenomena is not considered a serious science, some are continuing their research.

“At this stage, we have no counterargument to arguments that it is just a coincidence,” said Naoyuki Yada, associate professor of thermal engineering and earthquake prediction at the Kanagawa Institute of Technology in Atsugi, Kanagawa Prefecture. “But it seems all animals, including humans, are equipped with the ability to sense a big vicissitude in the environment.”

In his lab, Yada keeps two cats, a black one and a white one, with pedometers around their necks to monitor their activities.

They are usually docile, with pedometer readings of only dozens of steps a day.

But they displayed unusual behavior on March 9 last year, two days before the magnitude-9.0 earthquake struck northeastern Japan.

The count was nearly 400 for the white cat and around 500 for the black cat, even though they had been put in a cage that day.

When an aftershock measuring an upper 5 on Japan’s seismic scale of 7 shook Chiba Prefecture on the night of March 14, the counts for the white cat and black cat were 319 and 251, respectively.

Lungfish, goldfish, catfish and rats in the lab, which are observed with infrared ray sensors, were found dozens of times more active than usual.

Yada started studying animals for possible precursors 18 years ago. He conducted research under Wadatsumi, who died in January 2011.

Yada’s research found that the chances of an earthquake occurring within three days after cats showed erratic behavior, which is defined as more than 300 counts, are 64 percent for the white cat and 74 percent for the black cat.

Catfish’s accuracy rate tops 80 percent when at least 200 counts were recorded. Fish activity is counted each time it crosses the place where an infrared ray sensor was installed in the tank.

“The only way for us to lead to successful earthquake prediction through animals is to discover regularities by accumulating data piece by piece,” he said. “We are still in a stage before that.”

Yada this year began a project to send free kits to raise catfish to junior high and senior high schools across Japan to create a network of observation points.

He plans to release details of the monitoring activities on the Internet.

Since 1965, the central government has spent about 300 billion yen (3.7 billion) on research for earthquake predictions. But it has so far failed to produce tangible results.

By SHOJI NOMURA/ ASAHI SHIMBUN WEEKLY AERA