Two thousand miles east of the coast of Argentina, Gough Island rises out of the Atlantic Ocean in an awesome display of ancient volcanic activity. A green carpet of windswept mosses and grasses covers 35 square miles of jagged peaks and steeply sloping valleys. Waterfalls spill out of craggy cliffs and fall hundreds of feet to the sea, which runs uninterrupted for another 1,700 miles before crashing into the tip of South Africa. It is one of the most remote places on our planet.

Four miles west of the University of Wisconsin– Madison campus, the Charmany Instructional Facility is a low-slung labyrinth of concrete hallways lined by bright fluorescent lights and permeated with a smell that is equal parts animal and antiseptic. Part of the UW School of Veterinary Medicine, Charmany is nearly half a world away from Gough Island (pronounced “Goff ”). Yet the two locations share a common trait— they both are home to the largest mice on Earth.

In terms of body size and weight, Gough Island mice are twice the size of their mainland cousins, notes Bret Payseur, a geneticist with a joint appointment in CALS and the School of Medicine and Public Health. “The amazing thing about them being twice the size is that they’ve only been on the island a couple of hundred years,” he says. The island’s early rodent settlers were a more moderate-sized strain of Mus musculus, house mice stowaways in the holds of sealing ships from Western Europe. But somewhere along the line, Gough Island mice outgrew that ancestry—doubling in size over the course of only a few hundred generations. “That’s incredibly rapid evolutionary change,” Payseur says. “It’s some of the most rapid that I know about.”

In the canon of origin stories, however, this tale reads more like a mystery. How did the Gough Island mice get so big so quickly? It could be that a genetic mutation proved so advantageous that huge mice became the norm. Or maybe conditions on the island favored preexisting genetic traits that had lain dormant until the mice became castaways. For the time being, however, the Gough mouse story is transcribed only in A’s, T’s, C’s and G’s—the nucleic acids that write genetic code. Payseur hopes to translate that text. What he finds could not only shed light on evolution in action. It could also help illuminate the genetic mechanisms underlying human metabolic diseases like obesity and diabetes.

The Island Rule

While Gough Island mice are unusually large, it isn’t unusual for small animals on islands to grow bigger than their mainland counterparts. The phenomenon is often referred to as the “island rule,” which states that, in general, small animals tend to get bigger and large animals tend to get smaller once they’ve been island castaways for some period of time. There are, of course, exceptions. But from giant Komodo dragons to extinct pygmy mammoths, examples of the island rule run throughout the animal kingdom.

The gigantism effect of this rule seems to be especially pronounced in rodents. Human history is full of daring adventure on the high seas involving fearless mariners and the obligatory stowaways—mice and rats. As a result, the world’s islands are full of transplanted rodents. Biologist J. Bristol Foster first posited the island rule in a 1964 paper in the journal Nature, titled “The Evolution of Mammals on Islands.” In his study, Foster looked at 69 populations of island mice off the coasts of Western Europe and North America. The mice in 60 of those populations were measurably larger than their mainland cousins. Since that study, time and again, scientists find mice and rats on islands that are markedly bigger than genetically similar mainland populations.

This is notable because, in evolution, random genetic mutations or suddenly shifting environmental conditions can lead a species down a certain path. Which means that chance plays a big role in charting a species’ history. “If you ‘run the tape’ once and go back and run it again,” Payseur says, “you would expect different outcomes because of that role of chance.” When patterns like the island rule appear in evolution, he says, “People get very excited. It suggests that what underlies the patterns is a common mechanism that would tell us something important about how evolution works.”

Payseur’s scientific background is anchored in evolutionary biology, and the natural history of species on islands has fascinated him throughout his career. After early work with primates in Madagascar, Payseur realized that, while there is a lot one can do in primate research, keeping captive colonies of lemurs in a lab and breeding the thousands of crosses needed to actually get at answers wasn’t one of them. So he turned his attention to mice.

“The great thing about house mice—and I know most people don’t think house mice are great—is that the strains or lines of mice that people study in the lab are descended from wild house mice, including the wild mice that often inhabit islands,” Payseur says. “So they’re kind of cousins evolutionarily and share a lot of the same traits. That means we can use the genetic tools developed for the lab strains of mice to understand what’s happening in wild mice.”

He’s looking to these small creatures to answer some very big questions. “In the very long term, what I would like to answer with this research is, ‘What types of genetic changes are responsible for the extreme body size on islands?” Payseur says. “Are they the same on different islands? Do we see the same genes popping up over and over again, or do organisms take different paths to get big?”

Knowing that he would have the time, money and resources to deal with only a single strain of island mouse at a time, Payseur decided to start with the most extreme example of the island rule that he could find. He turned to colleagues who studied house mice in the field—and every one of them pointed him to Gough Island.

An Incredible Journey

Most researchers simply order mice via catalog, usually from what Payseur calls “the world center for mouse genetics,” the Jackson Laboratory in Maine. A copy of their glossy catalog lets researchers pick trait-specific lines of mice, from body size and coat color to preassigned conditions like immunodeficiency. Then, simply place an order and wait a few days for the mail to arrive. Gough Island mice aren’t in that catalog. Which means that Payseur had to figure out a way to get mice from an incredibly remote island with a grand total of six to eight full-time human residents, all of whom were busy with their year-long stint staffing the South African National Antarctic Programme’s weather station.

The solution came in the form of an unusual and macabre adaptation of behavior in Gough Island mice. In addition to developing bigger bodies in their few hundred years on the island, they have also developed an appetite for bigger food—the chicks of nesting seabirds, which they, quite literally, nibble to death. Luckily for Payseur, there are quite a few people concerned about those seabirds.

Gough Island is officially a possession of Britain and part of the Dependency of Tristan de Cunha. It is also listed as a World Heritage Site by the United Nations Educational, Scientific and Cultural Organization, which recognizes Gough as a pristine, primarily untouched ecosystem. Its towering cliffs, according to the UNESCO description of the island, “host some of the most important seabird colonies in the world,” from the endangered Tristan albatross to the Atlantic petrel to the Northern Rockhopper penguin. Under such circumstances, a population of non-native, quick-breeding, bird-eating mice is of grave concern—especially to the governments and scientists tasked with preserving the island’s biodiversity.

Peter Ryan, director of the Percy FitzPatrick Institute of African Ornithology at the University of Cape Town, South Africa, says that, especially where petrels and albatrosses are concerned, Gough Island mice are a threat to breeding populations. Ryan has been an honorary conservation officer in the Tristan de Cunha islands since 1989 and has witnessed the decline in seabirds firsthand. When Payseur reached out to him in 2008, Ryan was working with Richard Cuthbert, a scientist at the Royal Society for the Protection of Birds, on a census of sorts to help the British government plan an intervention—or, rather, an eradication.

The mice “were easy enough to catch,” Ryan wrote in an email recalling Payseur’s request. “They occur at very high densities and we’d been live-catching lots of mice to estimate their movements and densities and to conduct poison trials to ensure that all were susceptible to the poison bait.” Ironically, in order to study how best to kill them, the researchers had the live traps, food, bedding and other paraphernalia needed to keep the mice alive for study.

The “big issue” Ryan recalls, was shipping them. Eventually, the crew of the S.A. Agulhas, a South African Antarctic research vessel, agreed to give the mice a lift, but “Even this was a bit tricky, because we had to convince them that the mice wouldn’t be able to escape.” In the fall of 2008, 50 Gough Island mice boarded a boat and took the return trip to the mainland, specifically Cape Town, South Africa. After a lot of paperwork they were sent to Johannesburg, with inspections and quarantines and mountains of paperwork piling up as they made their way by plane to Europe, then to Chicago and, in a final car ride, to the campus of the University of Wisconsin–Madison, where postdoctoral researcher Melissa Gray was waiting.

That September, Gray had just begun her stint in Payseur’s lab. The idea of working with mice excited her, since, as with Payseur’s initial study of primates in Madagascar, the Channel Island foxes she had been working on promised to be a difficult study organism. When a mentor suggested she reach out to Payseur, Gray says, “It was a perfect connection.” She had a background working on island populations and the genetics of size and “Bret already had this project and nobody to work on it.” Plus, she wouldn’t have to wait long to get going. “I started in Bret’s lab in September,” Gray recalls, “and the mice arrived in late October.”

Immediately upon their arrival, the Gough Island mice alleviated any concerns about their suitability as a study subject. “Basically it was a cardboard box with some breathing holes and food stuffed inside,” Gray recalls. But when she opened the box, “It was amazing,” she recalls. Ryan had sent 50 mice off to Wisconsin. Forty-five survived the trip and, even better, they’d managed to produce a couple of litters along the way. They hadn’t even begun their experiment, and already the Payseur Lab was growing a colony of Gough mice. “In a way, we ended up with more than we started with, which is crazy with the amount of stress they were under,” Gray says.

After that initial excitement wore off, the real work began. First, Gray had to randomly breed several sets of mice to ensure that their large size was genetic and not the result of conditions on the island. When those lines came out as big as the wild-born mice, she could turn her attention to creating the first lab-raised line of Gough Island mice, inbreeding some promising strains of mice to create lines that were genetically identical, which makes gene mapping much easier. These mice would then serve as the lab’s breeding colony, slated as mates for lab mice with a mainland heritage.

One way to think about the process—to borrow a metaphor from Mark Nolte, a current postdoctoral researcher in the Payseur Lab—is to imagine two decks of playing cards, one red and the other blue, where each card is a gene. Each deck represents a chromosome, a long strand of DNA wrapped around proteins that carries genetic instructions from a parent to its offspring. When sexual reproduction occurs, each parent contributes a copy of one of their two chromosomes to their offspring.

Imagine the Gough Island mice as having two blue decks of cards—one deck for each chromosome—and the mainland mice as having two red decks. Their initial mating yields what’s called a “filial generation one,” or an F1 baby mouse with two distinct chromosomes, one with all blue cards and the other with all red cards. But when an F1 mouse mates with another F1 mouse, those decks get shuffled. These “filial generation 2,” or F2 mice, hold the first key to untangling the riddle of the evolution of Gough Island’s giant mice.

Continue reading this story in the Summer 2016 issue of Grow magazine.

Banner photo: Peter Ryan/University of Cape Town