World's Largest Rodent Has Surprising New Way of Fighting Cancer

On a planet full of animal oddballs, capybaras stand apart.

Sixty times heavier than their closest modern relative, the world’s largest living rodents are roughly the size of small adult humans. They spend their days munching grass along the riverbanks of South America, and they are chill enough to serve as chairs for countless other animals.

But what enabled capybaras to become gentle giants has been shrouded in mystery—until now.

In a new study posted on the pre-print service bioRxiv, a team of scientists from Colombia, Sweden, and the United States sequenced the capybara’s DNA and found hints of a growth system on overdrive. Their work also uncovered the genetic signature of a putative anti-cancer mechanism that may one day inspire new treatments.

Lead study author Santiago Herrera-Álvarez began studying capybaras while he was a Master’s student at the Universidad de los Andes in Bogotá. A severe drought in 2014-15 dried up many of Colombia’s rivers, leaving the countryside parched. With little vegetation for food, capybara numbers plunged.

Herrera-Álvarez’s interests, however, weren’t in the immediate effects of the drought. Instead, the event sparked his curiosity about how this ridiculously cute guinea pig-hippopotamus mashup evolved in the first place.

“The capybara is an iconic South American animal,” he says.

Building a Giant

The capybara’s ancestors evolved in Africa around 80 million years ago and arrived in South America 40 million years later. Its relatives are all normal-size rodents; for instance, the related rock cavies, which live in the scrublands of eastern Brazil, weigh in at only two pounds each.

Rodents tend to be tiny because smaller animals can hide better, and much larger predators may consider them not worth the effort, explains Duke University evolutionary biologist V. Louise Roth. But at the time the capybaras arrived in South America, the region was almost completely devoid of predators, which may have allowed their ancestors to start getting bigger.

“Without predators, the pressures keeping the rodents small are relaxed,” Roth explains.

According to the new research, the secret to exactly how the capybara could grow by more than an order of magnitude had long been hidden in its DNA. Caviomorphs—the subgroup of rodents that contains capybaras—all have a unique form of insulin.

Besides regulating blood sugar, insulin also tells cells to divide. Herrera-Álvarez and his colleagues found that capybaras didn’t have more insulin. Instead, millions of years of natural selection increased insulin's ability to tell their cells to divide, boosting their growth and giving rise to the shaggy, hundred-plus-pound animal.

Risk Management

Getting so big has its drawbacks, though. Besides requiring more food to support a larger body, the capybara had to contend with an increased cancer risk as it gained size.

If each cell has a fixed probability that it will become malignant, then animals with more cells should be more likely to develop cancer. Yet that’s not what happens. For instance, despite being thousands of times larger than mice, elephants are no more likely to develop cancer. It’s known as Peto’s Paradox, and biologists have uncovered several mechanisms that larger animals have evolved to stop cancer before it starts.

Scientists have discovered that Asian and African elephants, for example, are better at spell-checking their DNA when cells divide, which reduces the number of cancer-causing mutations. Bowhead whales, on the other hand, have evolved better mechanisms to keep cells from dividing unchecked.

Herrera-Álvarez’s team discovered that capybaras appear to have evolved a completely new tactic. Their genome showed signs that their immune system is far better at detecting and destroying cells that are dividing too rapidly. In other words, capybaras have evolved their own form of cancer immunotherapy.

“I was very surprised. I wasn’t expecting that the immune system might be involved,” he says.

“What they found seems really different from what happens in other animals,” says Vincent Lynch, an evolutionary cancer biologist at the University of Chicago. “Maybe it’s not as hard as we thought to evolve these anti-cancer pathways.”

Both Lynch and Roth praised the work, calling it thorough and creative, though they cautioned that the results are only preliminary and need to be followed up with more experiments back in the lab.

And as to whether capybaras can be officially be called giants among rodents, the jury is still out.

“There’s no definition of ‘giant’ by biologists,” Roth says. “In the end, I suppose it’s how impressed you are by them.”