Cats are different than other domesticated animals. Unlike other species tamed for either food or labor, cats specialized in becoming mooches. Sure they catch mice, but it's not like they do it for our sake. Despite these differences, many scientists believe that cats, like all domesticated animals, inherited certain genetic mutations from ancestors who were unafraid of humans. A new study identifies some of the genes that may be responsible for the differences between house cats and their wild ancestors.

The research, published today in the Proceedings of the National Academy of Sciences (paywall), follows closely on the complete annotation of the cat genome, released in the journal Gigascience this August. Both were the result of a huge international effort, involving nearly a dozen research institutions. The scientists weren't just trying to find out why kitties like us. The complete cat genome could improve understanding, and treatment, of the more than 250 diseases that afflict humans and cats in similar ways.

House cats aren't all that different from modern wildcats, the wild species most closely related to them. Wildcats have slightly larger brains, but in skeletal terms the two are nearly identical. (Most of the garish indoor cat breeds—from white-booted Birmans to long-coated Maine Coons, didn't exist before 200 years ago.) The biggest difference is in their personalities, which starts in the genes, says Stephen O'Brien, one of the paper's senior authors and chief scientific officer at the Theodosius Dobzhansky Center for Genome Bioinformatics in St. Petersburg, Russia. He says that cat domestication started about 10,000 years ago, with the spread of agriculture. Humans were creating sizable amounts of food waste, which attracted scavengers like wildcats. Some, says O'Brien, were genetically inclined to be friendlier, or at least less fearful, towards humans. Maybe they began to let our curious ancestors approach them as they were picking scraps of meat out of the bone pile, or perhaps a proto-kitteh even came in for a nuzzle.

By comparing the wildcat and house cat genomes, and looking for places where the house cat genome had undergone rapid changes, the researchers found three possible genetic links to that change in temperament. Compared to wildcats, house cats have more mutations on genes known to mediate aggressive behavior, form memories, and control the ability to learn from either fear or reward based stimuli. Cats with these traits would have mated with each other, repeatedly passing them along from parent to kitten until a significant population became distinct from their still-aggressive cousins.

"There's a big difference between house cats and wildcats," said Stephen O'Brien. "A house cat will sit on your lap, but a wild cat will hand you your behind." These genes were most active in the neural crest, a group of embryonic cells that become the spinal cord in adult vertebrates.

Not all of the genetic differences were related to behavior. Living with humans put other selective pressures on cats, including the addition of vegetables to their diet. "Wildcats are pretty unique in the mammal world because they are hyper carnivores," said Carlos Driscoll, a researcher at the National Institutes of Health and co-author of the study. "It's not just that they don't like eating non-protein foods, but it doesn't seem to do them any good if they do." House cats, on the other hand, do eat some plant matter, which probably came about from picking through our ancestors' rubbish. This is reflected not only physiologically—house cats have a slightly longer large intestine than wildcats—but also in genes that control the digestion of fatty plant matter, which are more active in domesticated cats.

In other domesticated animals, scientists have identified genetic changes connected to traits like floppy ears, curlier tails, or white spotting, that are not actively selected for, but seem to be connected to genes for things like docility, said Alex Cagan, who studies the genetic roots of domestication at Max Planck Institute in Leipzig, Germany, and was not involved with the new study. Many of these genes are active in the neural crest, and at least one of them—a gene linked to white spotting—also appears to be mutated in house cats, the new study found.

Learning why our kitties love us (read: are great mooches) is interesting, but the researchers are more excited about the implications for medicine. Cats have their own versions of everything from diabetes to HIV/AIDS, explains O'Brien, and their genome could help to develop better treatments for humans. O’Brien is one of the pioneers genetic research in animals, and helped establish the discipline of comparative genetics (paywall). In 2009, he also helped found the Genome10K project, which aims to sequence and fully annotate the DNA of 10,000 vertebrate species by 2015.

This is all very cool, but we're still a long way from knowing exactly what turned wildcats into lolcats. "Nobody is trying to say that these genes are all you need to make a domestic animal," Driscoll said. O'Brien compares what he and his colleagues are doing to the work of 19th century paleontologists, who were just learning how to reconstruct million-year-old skeletons. "We're just learning how to decipher the genome sequences we're finding," he said. "It's an exciting time to be in genetics."