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Cancer and Capybaras

Monday, April 12, 2021

Bogota (Colombia)

Capybara: the great giant resistant to cancer

Written by: Angela Possada-Swafford, El Tiempo

Even when they eat their own poop, it’s hard not to fall in love with a capybara. Even with a formal name like Hydrochoerus hydrochaeris, you cannot remain impassive when facing that cool rectangular head and that pair of eyes, narrowed as if in a constant fit of laziness, perched up there on the skull. These plant — and poop—eating animals are typically found in South American savannah landscapes and if casual observers find them irresistible, biologists are also being won over. They have learned, for example, that poop adds bacteria to help capybaras digest their previous meal. More importantly, scientists have identified them as the world’s largest species of rodent. That means several interesting things, one of which has to do with cancer.

Santiago Herrera and Andrew Crawford, two biologists at the University of Los Andes in Bogota, have brought their knowledge of gene evolution to the question of how this creature got to be roughly 2,000 times more massive than your typical mouse. What risks and benefits come with that growth and what does it imply about human growth? They have linked their research efforts with colleagues at the Broad Institute in Massachusetts to pioneer a sequencing the capybara’s genome.

It is well known that cancer, which is caused when cells divide uncontrollably and invade other tissues in the body, affects more than just humans. In fact, it also happens to other mammals, birds, reptiles, mollusks, and fish —including the shark, despite the myths that deny it. Neither do dogs, cats or horses escape the problem. Cancer biology indicates that the more cells an organism has, the greater the chance that mutations will occur in the DNA of those cells, and therefore the greater the chance of getting the disease.

By that logic, elephants and whales, with quadrillions of cells in their bodies, should be devastated by cancer. But what we see in real life is the other way around: the incidence of cancer in many giant animals is actually extremely rare or lower than was theoretically expected. This is a phenomenon known as “the Peto paradox “, after the British epidemiologist Richard Peto, who formulated it four decades ago.

So what mechanism is protecting elephants and whales? A group of researchers from the University of Chicago discovered part of the answer in 2015. According to them, elephants possess at the least 20 copies of an important gene called P53, whose function is to identify damaged DNA and trigger the death of those cells before they can turn into potentially cancerous mutations. Other researchers report that something similar happens in whales. Happy are they and happy are the elephants, but sadly, we humans only have one copy of this wonderful gene.

Capybaras and cancer

While he was working on his master’s degree at Crawford’s lab in Los Andes, Herrera asked himself whether something similar could be happening to the giant south American capybaras. The answer begins with the observation that these animals re not just huge rats without a tail, since capybaras and mice belong to two different rodent groups. Actually, its closest relative is the friendly guinea pig. But while a fat guinea pig weighs about three kilograms, an adult capybara can reach more than 65 kg.

Crawford and Herrera started by examining the basic biology of these animals, whose genes were still terra incognita. Since about 40 percent of all mammal species are rodents, they also are among the most diverse group in terms of species richness, shapes and sizes. The two scientists dived into the capybara genes, which meant sequencing them to determine the exact order of the base pair proteins, the “letters” that make up an organism’s DNA.

“The Broad Institute, as part of a giant mammalian genome sequencing project already had a draft of the capybara genome,” says Herrera. “I say ‘draft’ because within this project they did not sequence the entire genome but focused only on some regions. So, thanks to a grant of the Colombian Science Ministry that Dr. Crawford had won, where the idea was to generate genetic data for the conservation of capybaras, what we did was to take that draft and complete it.”

After four years’ worth of computational and statistical study to “curate” the genome, deciphering where each gene begins and ends, and correctly formulating key questions about biology and evolution, Herrera, with Crawford’s help, discovered that capybaras actually have multiple copies of three important genes in relation to cancer. One of them is in charge of reprogramming the malignant cells or erasing their evil features. The other two are part of the immune response against tumors that has been seen in some animals, and that works as a red flag to alert the immune system to kill the enemy.

“Our goal was to find these candidate genes, but we are yet to make experimental studies,” explains Herrera, who is currently pursuing a doctorate at the University of Chicago.

Their other finding, which will be published in the journal Molecular Biology and Evolution, is that this enviable protection system developed over time as the capybaras became bigger. That is why it was essential to understand how their ancestors went from the size of a guinea pig to that of the current capybara, a gigantism process that apparently was quite fast in evolutionary terms.

“We identified several genes involved in the growth and development of muscle and bone structures that are relevant to the modifications that the body requires to increase its size,” says Herrera. “Our results suggest that the gigantism in the capybara could have been caused by a period of rapid bone growth immediately after birth.”

These are the same genes that appear to be responsible for the extreme size differences in dog breeds and some fish, he adds. “That could suggest that vertebrates have a common mechanism that controls the evolution of accelerated growth.”

It’s not easy being big

For animal species, size comes at a cost. Among other things, you are living in the shadow of an increased risk of cancer. At the same time you have an uncertain resistance to the disease, uncertain because so far this resistance has only been studied in a few vertebrates, including some dinosaur fossils. One wonders if a mollusk like the colossal squid, for example, might have similar genetic weaponry. On the other hand, for all their magnificence, nature imposes a high price on all giants because the larger an organism is, the fewer are its numbers, which is why there are a lot more sardines than tunas. The dilemma, then, is that the fewer individuals there are, the fewer opportunities to produce new offspring.

However, an interesting 2015 Stanford study shows that animals do tend to evolve towards larger body sizes over time. Over the past 542 million years, for example, the average size of marine animals has increased by a factor of 150, according to Jonathan Payne, a paleobiologist at the Stanford School of Earth, Energy and the Environment. According to this idea, dinosaurs, if they existed today as such, would perhaps be even larger than their extinct ancestors. And would today’s capybaras ever get bigger than their four-million-year-old ancestor, a three-meter-long creature weighing and a ton, with teeth capable of generating three times more bite force than a tiger?

Such speculation is far removed from the glorious reality of meeting these bizarre-looking super rodents in their South American habitats. Around the plains of Colombia’s Casanare you can become infatuated with an entire family as they prepare for their morning bath. The little ones are impossibly adorable, elongated balls of brown fur on four short legs. They are creatures of the water — always in it, next to it or under it, and can actually hold their breath for up to five minutes. Upon reaching the center of the lake, the bunch submerge their head, leaving out their tiny ears and ajar eyelids. Their gaze is indifferent, as though none of this has anything to do with them. But of course it does. It is everything to do with them. They are not cows but like them, capybaras regurgitate food and keep chewing it. They are not beavers but like them, their teeth never stop growing.

“Seeing a capybara is a living testimony of the oddities that evolution can produce evolution,” Herrera says.

“Sometimes I need to make an effort to remember that they are rodents. I think they are a box of interesting surprises, and not for nothing are they emblematic of the South American fauna.”

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This article originally appeared in Spanish in the edition of El Tiempo Nov 29, 2020

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