By Stacy Rush ’11
Photos courtesy of Hopi Hoekstra

Hopi Hoekstra likes mice. A professor in Harvard’s Organismic and Evolutionary Biology department, Hoekstra is cracking the fundamental relationship between genes, traits and the effect of the environment on survival and reproduction. She originally worked with grizzly bears but quickly realized that to answer any large questions she needed large sample sizes – which necessitated the use of small organisms. Mice breed prolifically, are easily maintained in a lab setting – and, as Hoekstra adds, “they do happen to be very cute.”

While doing her postdoctorate, Hoekstra spent her time trapping rock pocket mice in sunny Arizona. She found that mice that lived on lava flows – dark colored rock – tended to have dark coats, while mice living in a lighter environment tended to have light coats. In other words, coat color “closely [matched] the environment in which [the mice] inhabit.” On the black lava “light-colored mice were big targets for predation because they are these bright golden beacons running around on this black lava.”

Photo courtesy by Hopi Hoekstra
Above: Hopi Hoekstra observing a field mouse.

But Hoekstra’s small subjects held big lessons in store.  Back in the lab, scientists tracked down a genetic source for the phenotype.  Hoekstra’s team pegged the melanocortin-1 receptor gene (Mc1R) as a key ingredient for the difference.  A mutation allowed mice to camouflage with their environments – an impressive example of evolution in action.

Hoekstra did not stop there. She found the same phenomenon in Floridian populations of beach mice. On Florida’s Gulf coast, mice displayed a dark coat color compared to mice on the Santa Rosa Island (Hoekstra et. al., 2006). The color difference was driven by selection for camouflage, as many predators are visual hunters. Hoekstra’s team pegged the same Mc1R gene as a contributor to the adaptive pattern. A single nucleotide change weakens the receptor so that it does not respond to signaling as well, creating a light-colored coat phenotype.

That the coat color of the mice matches their surroundings is only evident through field observations, which is why Hoekstra stresses the importance of a hands-on approach. “You just walk out on these brilliant white sand beaches where you see there’s very little vegetative cover and it just makes sense that mice that are lighter in color are going to be more camouflaged,” she says.    This research led National Geographic to hail Hoekstra as a new Darwin just in time for Darwin’s 200th birthday, which was this past year.

Photo courtesy of Hopi Hoekstra
Above: Camoflauge, a light mouse matching its environment.

Hoekstra has since branched out to study other mice characteristics, including tail length variation, reproductive traits, and behaviors. According to Jesse Weber, a graduate student in her lab, “every diverse thing you can think of for adaptation in rodents…is fair game in the lab.”

Weber is currently studying the evolution and genetics of instinctive burrowing in two species of Peromyscus, or deer mice. Peromyscus polionotus builds complex burrows while Peromyscus maniculatus builds simple burrows. The simple burrow consists of just one entrance while the complex burrow also contains an escape exit that is dug up to just below the surface. This allows the mice to make a hasty getaway in times of danger. When P. maniculatus and P. polionotus are crossed and then re-crossed, the hybrid progeny mice will build variations of the complex and simple burrows.    To enable observation of just this sort of behavior, the lab houses giant four-by-five feet sandboxes which Hoekstra calls “phenodomes” because “that’s where we measure phenotype.” The mice are put in the phenodomes for two days and allowed to build a burrow. They are then removed and researchers make a cast of their burrow using a kind of hardening foam. The cast is then studied just like any other morphological trait. “This is what Richard Dawkins calls an ‘extended phenotype’ – it’s not actually held within our skin, yet it’s controlled by genes,” explains Hoekstra.   For further research, the lab also has what Hoekstra calls a “mouse farm” – similar in concept to an ant farm. “You can videotape [the mice] burrowing in a two-dimensional structure and they will build these complex burrows,” Hoekstra says.

Reflecting on the challenges of her work, Hoekstra says that it is “very integrative. For any given project to get the complete picture of adaptation, it requires essentially working across disciplines. We do ecological work ….work at the organismal level … work at the developmental level down to the genetics and the molecular biology…. It’s hard in some sense to do all of it and all of it well.”   However, she adds, the combination of all these aspects of biology “makes our work fun.” As she said in National Geographic, “Opening a trap with a mouse is a little like Christmas morning.”

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