Research shows changes in mouse coat color were the result of nine mutations within a single gene

Published on March 15, 2013 at 1:48 PM · No Comments

For deer mice living in the Nebraska Sandhills, color can literally be the difference between life and death.

When they first colonized the region, the dark-coated mice stood out starkly against the light-colored, sandy soil, making them easy prey for predators. Over the next 8,000 years, however, the mice evolved a new system of camouflage - lighter coats, changes in the stripe on their tails and changes in the extent of pigment across their body - that allowed them to blend into their new habitat.

Now Harvard researchers are using their example to answer one of the fundamental questions about evolution - is it a process marked by large leaps - single mutations that result in dramatic change in an organism - or is it the result of many smaller changes that accumulate over time?

As described in a March 15 paper in Science, a team of researchers, including former Postdoctoral Fellow Catherine Linnen, now an Assistant Professor at the University of Kentucky, and led by Professor of Organismic and Evolutionary Biology and Molecular and Cellular Biology Hopi Hoekstra, were able to show that the changes in mouse coat color were the result not of a single mutation, but at least nine separate mutations all within a single gene.

"The findings demonstrate how the cumulative effect of natural selection, acting on many small genetic changes, can produce rapid and dramatic change," Linnen, the first author of the paper, said. "This helps us to understand, from a genetic perspective, the uncanny fit between so many organisms and their environments-by acting on many small changes, rather than a handful of large ones, natural selection can produce very finely honed adaptations."

Surprisingly, Hoekstra said, that honing occurred in a single gene.

The role of this gene, called agouti, in camouflage was first discovered by Linnen, Hoekstra and colleagues in 2009, and it is responsible for changes in pigmentation in the coats of many animals. Every domesticated black cat, for example, has a DNA deletion in the gene.

What surprised Hoekstra and her team, however, wasn't that the gene was involved, but that each of the nine mutations were tied to a unique change in the animal's coats, that all the new mutations led to more camouflaging color, and that the mutations occurred in a relatively short, 8,000-year timeframe.

"Essentially, it seems as though these mutations - each of which makes the mouse a little lighter and more camouflaged - have accumulated over time," Hoekstra said.

Focusing on these mutations, researchers then examined the DNA of natural populations of the mice to determine whether the mutations are actually beneficial.

"For each of the mutations associated with color change, we also find a signal that's consistent with positive selection," Hoekstra said. "That implies that each of the specific changes to pigmentation is beneficial. This is consistent with the story we are telling - about how these mutations are fine-tuning this trait."

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