A team of researchers have been able to show that the changes in mouse coat color are the result not of a single mutation but of at least nine mutations 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," said former Harvard postdoctoral fellow Catherine Linnen, now an assistant professor at the University of Kentucky. "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, that honing occurred in a single gene. The role of this gene, called agouti, in camouflage was first discovered by researcher 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 that gene. What surprised the researchers, 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 time frame. "Essentially, it seems as though these mutations - each of which makes the mouse a little lighter and more camouflaged - have accumulated over time," Hopi Hoekstra, Harvard professor of organismic and evolutionary biology and molecular and cellular biology, 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." While the findings offer valuable insight into the way that natural selection operates, Hoekstra said that they also highlight the importance of following research questions to their ultimate end. "The question has always been whether evolution is dominated by these big leaps or smaller steps," she said. "When we first implicated the agouti gene, we could have stopped there and concluded that evolution takes these big steps as only one major gene was involved, but that would have been wrong. When we looked more closely, within this gene, we found that even within this single locus, there are, in fact, many small steps." Going forward, Hoekstra said, her team hopes to understand the order in which the mutations happened, which would allow it to reconstruct how the mice changed over time. "For evolutionary biologists, this is exciting because we want to learn about the past, but we only have data from the present to study it," she said. "This ability to go back in time and reconstruct an evolutionary path is very exciting, and I think this data set is uniquely suited for this type of time travel." Taking the time to understand not only which genes are involved but which specific mutations may be driving natural selection, Hoekstra said, can give researchers a much fuller picture of not only the molecular mechanisms by which mutations alter traits, but also the evolutionary history of an organism. "By doing this, we've discovered all kinds of new things," she said. "While we often think about changes happening in the entire genome, our results suggest that even within a very basic unit - the gene - we can see evidence for evolutionary fine-tuning."