That not only gives us a more realistic version of Kipling’s tales, but also speaks to one of the most important evolutionary issues of all—how genetic changes lead to physical changes, how DNA sculpts bodies.
Mallarino showed that even before the mice are born, their stripes are already set. Dark and light bands appeared on their gray embryonic skin, and over a thousand genes were more active in one of these regions than the other. Some were more active in the dark stripes and were known to be involved in making dark pigments—so far, so obvious. But another gene, known as Alx3, was almost seven times more active in the light stripes than the dark ones—and that was a surprise.
“I’ve been studying pigmentation for 15 years, and I’ve never heard of this gene being involved,” says Hopi Hoekstra, who led the study. It’s not like Alx3 is a new gene, either. Other scientists have studied it extensively, showing that it helps to sculpt the heads and faces of mice, and that mutant versions can lead to cleft palates. And yet, in all those experiments, no one had noticed any differences in color. “But many of those studies had been done in a strain of albino mice,” says Hoekstra. “Once we pieced that together, it all made sense.”
By using several techniques to switch Alx3 on or off, the team showed that it works by suppressing another gene called Mitf. In doing so, it stops the development of melanocytes—the cells in the skin that produce dark pigments. That’s what lightens the mouse’s fur, creating light stripes amid the dark ones.
The same thing happens in chipmunks. Striped mice and chipmunks look very similar but the latter is a type of squirrel, and separated from the mice by around 70 million years of evolution. It seems that all rodents use Alx3 to create light fur on their flanks and bellies, but these two groups have independently recruited the gene to also make light stripes on their backs.
What about other mammals? There are a lot of striped rodents that vary in the thickness and number of their stripes, from single-striped grass mice to thirteen-lined ground squirrels. It’s easy to imagine that by tweaking where Alx3 is active, you can get a wide diversity of patterns. Mallarino’s team even got their hands on skin from a zebra, and found some signs that Alx3 is more active in its white stripes than its dark ones. “We had a sample size of one, though,” says Hoekstra, “but it’s certainly possible that this is also involved in more diverse stripe patterns.”
That’s not to say that Alx3 is the only game in town. In 2012, another team showed that two different genes—Taqpep and Edn3—control the coat patterns of cats, from cheetahs to tabbies. These genes also act in a different way: while Alx3 affects how melanocytes mature, Taqpep and Edn3 prompt the same melanocytes to switch from making light pigments to dark ones.