When Marvel Comics created a short superhero who could heal horrific injuries, perhaps instead of “Wolverine”, they should have named him “African spiny mouse”. These tiny rodents can jettison strips of skin from their own hides when captured by predators, and heal those same wounds with extraordinary speed.
Healing powers are common in the animal world. Salamanders and starfish can regrow lost limbs, while some flatworms can regenerate their bodies from a single cell. But mammals lag behind – while some species can grow back a lost tail, when most of us lose our body parts, we do so permanently. The spiny mice are an exception.
Biologists have noted that these rodents have very weak skin, which seems to slough off easily when they are handled. Led by these anecdotal reports, Ashley Seifert from the University of Florida has studied the skin-shedding ability in greater depth, focusing on two species: Kemp’s spiny mouse (Acomys kempi); and Percival’s spiny mouse (Acomys percivali).
If you only looked at mammals, you could reasonably believe that the chisellers have inherited the earth. Of all the various species of mammals, forty percent are rodents. Rats, mice, squirrels, guinea pigs… all of them have the same modus operandi. They gnaw their way into their food with self-sharpening chisel-like teeth.
Whether tiny gerbil or huge capybara, rodents eat with the same special teeth. The upper and lower jaws each have a single pair of incisors that grow continuously through their lives. The front of each tooth is made from hard enamel, while the back is made of soft dentine. As the rodent gnaws, the incisors scrape at each other, and the dentine wears away faster than the enamel. This creates a permanently sharp edge, useful for cracking into wood, nuts and flesh alike. Once gnawed, the rodent passes its food to the back of their mouths to be chewed by grinding molars.
But on the Indonesian island of Sulawesi, Jacob Esselstyn has discovered a new species of rodent that radically departs from this universal body plan: a “shrew-rat” that he calls Paucidentomys vermidax.Its name –a mash-up of Latin and Greek—gives a clue to its lifestyle. It means “worm-devouring, few-toothed mouse”.
You enter a room with two cages. One contains a friend, who is clearly distressed. The other contains a bar of chocolate, which clearly isn’t. What do you do? While a few people would probably go for the chocolate first (and you know who you are), most would choose to free the friend. And so, it seems, would a rat.
Inbal Ben-Ami Bartal from the University of Chicago found that rats will quickly learn to free a trapped cage-mate, even when they get nothing in return, or when there’s a tasty chocolate distraction around. Bartal thinks that the rats conduct their prison breaks because they empathise with one another. This ability to understand and share the feelings of another individual is found in humans, apes, elephants, dolphins and other intelligent animals. It seems that rats belong in this club too.
The naked mole rat must be one of the strangest mammals in existence. They live in underground colonies like those of ants and bees, with a fertile queen lording over sterile workers. They feel no pain in their skin, they live unusually long lives, they can cope with chokingly low levels of oxygen, and they seem to be immune to cancer. Their sight is poor, they can’t control their body temperature very well, and their teeth jut out beyond their lips. And they look like wrinkled sausages.
Now, just when you thought they couldn’t get any weirder, we can add another bizarre trait to the naked mole rat’s extensive list: they have really rubbish sperm.
A shark continually grows new teeth. Those at the front of its mouth fall away, only to be replaced by fresh rows that move forward like conveyor belts. By contrast, we humans only have two sets of teeth. The first falls away during childhood leaving a second set to last us for the rest of our lives. Most mammals are like us, but there are some notable exceptions.
The silvery mole rat of Kenya and Tanzania continually replaces its molars in an unsettlingly shark-like way. New ones sprout from the back of its jaw and slowly make their way forwards. The front ones, having been ground away, are absorbed.
The African crested rat is a thief, but its loot only becomes obvious if you take a bite out of it. Doing so would give you a mouthful of ouabain, a poison so strong that it can kill an elephant. The rat doesn’t make the poison itself. Instead, it pilfers it from the local Acokanthera schimperi tree. It gnaws on the roots and bark, chews them up, and slavers a coarse toxic gel onto the special hairs on its flanks. Local people use the same poison to coat their arrowheads. The rat uses it as a chemical shield.
The crested rat is found throughout eastern Africa. It is normally sluggish but when threatened, it puts on a vivid display. It pulls its head back, turns sideways onto its attacker and parts the grey fur on its flanks using special muscles. These actions draw attention to a leaf-shaped crest of brown hairs on its side, which are encircled by a “target” of black and white. It’s almost as if the rat is daring a predator to bite it.
Any animal that takes up the invitation is in for trouble. Domestic dogs do so from time to time, and they end up stumbling about and frothing at the mouth. They often die of rapid heart failure. In two cases where the animals survived, they took weeks to recover. For these reasons, people have long thought that the rat is poisonous; now Jonathan Kingdon from the University of Oxford has proved them right.
Since 1948, people have been poisoning unwanted rats and mice with warfarin, a chemical that causes lethal internal bleeding. It’s still used, but to a lesser extent, for rodents have become increasingly resistant to warfarin ever since the 1960s. This is a common theme – humans create a fatal chemical – a pesticide or an antibiotic – and our targets evolve resistance. But this story has a twist. Ying Song from Rice University, Houston, has found that some house mice picked up the gene for warfarin resistance from a different species.
Warfarin works by acting against vitamin K. This vitamin activates a number of genes that create clots in blood, but it itself has to be activated by a protein called VKORC1. Warfarin stops VKORC1 from doing its job, thereby suppressing vitamin K. The clotting process fails, and bleeds continue to bleed.
Rodents can evolve to shrug off warfarin by tweaking their vkorc1 gene, which encodes the protein of the same name. In European house mice, scientists have found at least 10 different genetic changes (mutations) in vkorc1 that change how susceptible they are to warfarin. But only six of these changes were the house mouse’s own innovations. The other four came from a close relative – the Algerian mouse, which is found throughout northern Africa, Spain, Portugal, and southern France.
The two species separated from each other between 1.5 and 3 million years ago. They rarely meet, but when they do, they can breed with one another. The two species have identifiably different versions of vkorc1. But Song found that virtually all Spanish house mice carry a copy of vkorc1 that partially or totally matches the Algerian mouse version. Even in Germany, where the two species don’t mingle, a third of house mice carried copies of vkorc1 that descended from Algerian peers.
Not Exactly Pocket Science is a set of shorter write-ups on new stories with links to more detailed takes, where available. It is meant to complement the usual fare of detailed pieces that are typical for this blog.
Plague-running mice create epidemics
The bacterium behind bubonic plague – Yersinia pestis – has a notorious track record for massacring humans, creating at least three major pandemics including the Black Death of the 14th century. But it’s mainly a disease of rodents and it regularly infects the black-tailed prairie dogs of North America. It’s an enigmatic killer. It will remain relatively silent for years before suddenly exploding into an epidemic that kills nearly all the prairie dogs in infected colonies within a few weeks. Now Daniel Sakeld from Stanford University has found the culprit behind these lurk-and-kill cycles – the tiny grasshopper mouse.
Prairie dog colonies, and their diseases, are generally isolated from one another. Even though Yersinia is very persistent, it eventually fades away unless it finds a new group of hosts. The grasshopper mouse provides it with just such an opportunity by acting as an alternative and highly mobile host for Yersinia. It’s a plague-runner. By scampering across the grasslands, it inadvertently creates a network between otherwise unconnected colonies, opening up corridors for Yersinia to spread.
By creating a mathematical model, and observing both rodents in the wild, Sakeld found that when the mouse is absent, only a small proportion of prairie dogs are plagued by plague. In these conditions, infections spread very slowly during fights and hostile takeovers between neighbours. When mouse numbers pass a threshold, fatal plague epidemics are virtually guaranteed.
The numbers of grasshopper mice in the grasslands rises and falls over time, a cycle that could spell life or death for the prairie dog. These patterns of lengthy lurking and sudden death are also shared by many other deadly diseases like anthrax and hantaviruses. In these cases, alternate hosts like the grasshopper mouse might also be involved in the sudden rise of deadly epidemics.
Reference: PNAS http://dx.doi.org/10.1073/pnas.1002826107
Events occur in real time – watching the birth of mutations
Life is a massive game of Chinese whispers – information is constantly being passed on and as this happens, errors build up. Every time a cell divides in two, its genetic information is copied and there’s a small chance that mistakes (or ‘mutations’) will creep in. Some of these mutations will be beneficial, others will be fatal. Either way, they provide fuel for evolution, producing the variation that natural selection acts upon.
Now, Marina Elez from University Paris Descartes Medical School has found a way to spot mutations in real time. She can look at dividing cells and literally watch the moment when mutations show up across the entire genome. The technique works in bacteria, and it could be expanded to study the birth of mutations in more complex cells or even cancers.
Studying mutations isn’t easy. They’re very rare and most don’t produce any noticeable effects that would give away their presence. More often not, they’re repaired by proofreading proteins, which watch for errors in copied DNA and edit them back into shape. Elez realised that these proofreaders could lead her to the location of mutations – all she needed to do was follow. She focused on one bacterial proofreader called MutL, which forms large clusters around mutations that it can’t repair. Elez tagged MutL with a molecule that glows in the dark. The result: bacteria that give off tiny pinpricks of light at every point of their genome with an irreparable mutation.
By counting these bright dots, Elez could estimate the mutation rate in her bacteria. And fortunately, her estimate was a good match for the predictions of earlier studies. Elez also thinks that the approach should work in other living things because proofreading proteins like MutL are very similar from species to species. The technical challenges might be greater in more complicated cells, but the principle of watching mutations in real time is sound. And that opens up all sorts of possibilities. You could, for example, look at tumours, to see when and where the genetic changes that create a cancer will emerge.
Reference: Current Biology http://dx.doi.org/10.1016/j.cub.2010.06.071
Today’s mammals are facing the twin threats of a rapidly warming planet and increasingly intrusive human activity. As usual, the big species hog the limelight. The world waits on bated breath to hear about the fates of polar bears, whales and elephants, while smaller and more unobtrusive species are ignored. But smaller mammals are still vital parts of their ecosystems and it’s important to know how they will fare in a warmer world. Now, thanks to Jessica Blois from Stanford University and a hoard of new fossils, we have an idea. As they say, all this has happened before…
It’s 1964, and a group of Canadian scientists had sailed across the Pacific to Easter Island in order to study the health of the isolated local population. Working below the gaze of the island’s famous statues, they collected a variety of soil samples and other biological material, unaware that one of these would yield an unexpected treasure. It contained a bacterium that secreted a new antibiotic, one that proved to be a potent anti-fungal chemical. The compound was named rapamycin after the traditional name of its island source – Rapa Nui.
Skip forward 35 years and rapamycin has made a stunning journey from the soil of a Pacific island to the besides of the world’s hospitals. Its ability to suppress the immune system means that it’s given to transplant patients to stop them from rejecting their organs and its ability to stop cells from dividing has formed the basis of potential anti-cancer drugs. But the chemical has an even more interesting ability and one that has only just been discovered – it can extend lifespan, at least in mice.
David Harrison, Randy Strong and Richard Miller, leading a team of 13 American scientists, have found that capsules of rapamycin can extend the lifespans of mice that eat them by 9-14%. That’s especially amazing given that the mice were already 20-months-old at the time of feeding, the equivalent in mouse years of a 60-year-old human.
There will undoubtedly be headlines that proclaim the discovery of the fountain of youth or some such, but it is absolutely critical to say up front that this is not a drug that people should be taking to extend their lives. Rapamycin has a host of side effects including, as previously mentioned, the ability to suppress the immune system. Harrison says, “It may do more harm than good, as we know neither optimal doses nor schedules of when to start for anti-ageing effects.” So the new discovery doesn’t put an anti-ageing pill within our grasp. It’s far better to see it as a gateway for understanding more about the basic biology of ageing, and for designing other chemicals that can provide the same benefits without the unwanted risky side effects.
Nonetheless, it’s still very exciting, especially since the nutrition market is already awash with supplements that claim to slow the ageing process but which have little evidence to back their claims. Likewise, scientists have tested a number of different chemicals but the few positive effects have typically been small or restricted to a specific strain of mouse. Rapamycin is different – as Harrison himself explains, “no other intervention has been this effective when starting so late in life on such a diverse population.”