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An oldfield mouse. By Vera Domingues/Hopi Hoekstra
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Shape of an oldfield mouse burrow. From Weber et al, Nature.

To catch oldfield mice, Hopi Hoekstra needed a long tube and quick reflexes. The mice dig burrows in sandy fields and beaches of the southern USA. They build a round nest chamber, an entrance tunnel that connects it to the outside world, and an escape tunnel that extends in the opposite direction and ends just below the surface. If Hoekstra put a tube down an entrance and blew through it, a mouse would erupt from of its escape hatch in a shower of sand.* And because the burrows are so standardized, it was easy to predict where the mouse will emerge.

Back in the lab, Hoekstra’s team, including Jesse Weber and Brant Peterson, made a surprising discovery. The shape of the burrows is controlled by a surprisingly small number of genes. Three small parts of the mouse’s genome control the size of its entrance tunnel, each one accounting for around 3 centimetres of length. And just one small region determines whether or not the mouse builds an escape tunnel.

We’re used to the fact that genes can shape bodies and behaviour, and that scientists can find these associations. But our bodies and behaviour reshape the world around us. Beavers, for example, build dams, which means that beaver genes can redirect the flow of entire rivers.

This is what Richard Dawkins called an “extended phenotype”. A creature’s phenotype is the collection of its traits, from its body shape to its behaviour. Its extended phenotype is the stamp it make upon its environment, such as beaver dams, bird nests, spider webs… and mouse burrows. None of these things have genes themselves, but genes clearly influence their construction. In 2004, Dawkins wrote, “Twenty-one years ago, I said that nobody had done a genetic study using animal artefacts as the phenotype. I think that is still true.”

It’s not true anymore: Hoekstra’s team have done exactly what Dawkins asked for. They’ve explored the genetics of an inanimate object.

The project is close to Hoekstra’s heart. It began in her garage back in 2005, when she and Weber first built large sandboxes in which captured mice could built their burrows. “We called them our phenodomes,” she says. The duo would then evict the mice and fill the burrows with an expanding foam (“We called it phenofoam”). The foam hardened into casts, which now fill the team’s attic space in their hundreds. The casts confirmed that the mice build incredibly consistent burrows, even if they had been raised in the lab and never seen sand before. It seemed likely that their home-building instincts were strongly influenced by their genes.

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Jesse Weber with some phenofoam casts. By Ed Yong

Weber started looking into the genes behind the burrows by breeding oldfield mice with closely related deer mice. This species builds much simpler burrows with shorter entrances and no escape tunnel. These were probably the original specs, and the oldfield mouse added deluxe features during its evolution.

Today, the two species live in different habitats, but they can still mate if they meet one another. Weber found that these first-generation hybrids dig oldfield-style burrows, with long entrances and escape tunnels. This suggests that the alleles (version of a gene) behind the newer behaviours take dominance over their older counterparts.

Weber then mated the hybrids with more deer mice and analysed the genomes of these second-generation animals. He discovered three separate genetic regions that affect the length of the entrance tunnel. “We were pretty surprised,” says Hoekstra. “We definitely didn’t expect that each of those regions makes the burrow 3 centimetres longer, or that they work additively and contribute equally.”

On the other hand, Weber found that just one region governs the escape tunnel. If mice have at least one of the dominant oldfield alleles at this site, they are 30 percent more likely to build a getaway route, and around half of the second-generation hybrids did so. That makes the escape tunnel a “Mendelian trait”, where inheriting the dominant version of a gene from either parent produces the dominant form of the trait. Other examples include a cleft in your chin, or whether you can roll your tongue.

All four regions sit on separate chromosomes and are independent of one another. “These two components of a burrow–the entrance and escape tunnel—are completely separable,” says Hoekstra. This suggests that the complex nature of the burrow could have arisen by putting together different modules that evolved separately. “You don’t need all that many starting pieces but if you combine them in different ways you get a lot of diversity.”

“It’s great work. There are very few other examples of genes for naturally occurring variation in behaviour,” says Marla Sokolowski, who has found a few in fruit flies. “When I started similar work in the 1980s, I was told that there was no way I’d ever find a gene that influences behaviour that varies naturally. Their effects would be so small that you’d never find them.”

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Oldfield mouse, by J.B. Miller, Florida Park Service

Three of Hoekstra’s lab members are now racing to find the specific genes responsible for the burrow architecture—each of the four regions might contain just one gene, or a cluster of them When that’s done, they can start to answer some burning questions. Remember that the entrance tunnel has to be just the right length, and the escape tunnel must go right up to the surface but never actually break through. So how does such a small number of genes control such seemingly complicated behaviour?

“That’s the million dollar question,” says Hoekstra. “Right now, it’s all speculation but our favourite candidate gene is one that could be involved in motivation or addictive behaviour. One hypothesis is that the two species of mice all have the same neural circuitry but one is more motivated to finish the product. But I don’t think it’s quite that simple.”

Hoekstra’s student Hilary Metz is studying the rodents’ behaviour and testing them with different drugs to see how they differ from the deer mice. “Anecdotally, we know that the oldfield mouse is more active, which is the inverse of what you’d expect if it was just a change in activity.”

Other lab members are following up on the discovery in different ways. (Hoekstra’s team are a model of interdisciplinary science, with many scientists from varying backgrounds, tackling the study of evolution from different angles.) Student Zain Ali is going to add back the old versions of the burrow-related regions into oldfield mice to see what happens. He’s also trying to see what parts of the rodents’ brains are activated when they burrow, and what genes are active in those areas. And Brant Peterson is putting the mice in narrow glass-paned ant farms, so he can actually film them burrowing and quantify any differences in their movements.  “He has even taken X-ray videos of these mice digging,” says Hoekstra.

* To clarify, they didn’t blow the mice out. They blew, which spooked the mice, which then jumped out on their own!

Reference: Weber, Peterson & Hoekstra. 2013. Discrete genetic modules are responsible for complex burrow evolution in Peromyscus mice. Nature