White Horses and other Beautiful Mutants

Here's my weekly column, which will also run Monday on the cover of the Philadelphia Inquirer's Health and Science section:

There was no hanky-panky involved when a fairy-tale white foal was born to two brown Standardbreds at the Four Winds Farm in New Jersey. DNA tests confirm that the snowy foal, born May 6, is a mutant, but that's nothing to be ashamed of. So are most humans, according to a new analysis.

Geneticists and veterinarians say this unusual foal's lack of color comes from a spontaneous or "de novo" mutation — a spelling error in the DNA carried in either the sperm or egg from which he was conceived.

"De novo mutations are the fuel of evolutionary change," said Joshua Akey, a geneticist from the University of Washington. He's been studying de novo mutations in humans, and found hundreds of them. Most of these new mutations haven't caused anything as dramatic as this foal's white coat, but Akey says they are probably influencing our susceptibility to diseases.

There are no exact numbers for the frequency of white foals, but experts say it's extremely rare to see one crop up spontaneously. Most horses that appear white are really pale gray, said Hannah Galantino-Homer, a veterinarian and researcher with the Penn Veterinary School's New Bolton Center. Gray horses tend to fade as they age. (That may explain why there are both a pale horse and a white horse ridden by the four horsemen of the apocalypse — they truly are different colors.)

White horses can be the product of several possible mutations, said Galantino-Homer. Albino horses result from mutations that prevent production of the compound melanin — a pigment that gives color to skin, hair, and eyes. But such animals usually have pink eyes. This foal's eyes are blue.

Other mutations that can lead to white animals prevent pigment-producing cells from migrating around an embryo during development, Galantine-Homer said. Such mutations also crop up in mice, pigs, and dogs.

Melanin-producing cells, called melanocytes, form along the proto-spinal cord of an embryo — what's called the neural crest, she said. During development, those cells normally receive signals that prompt them to migrate away and become distributed over the embryo.

If a mutation interferes with this process, an animal can come out white with a smattering of color on the head or along the mane. A few animals with these mutations are also born deaf, Galantino-Homer said. That's because some melanin-producing cells are important for inner-ear development.

There's no indication the white foal is deaf. The mutation he carries is probably located in a gene called KIT, said Cornell University veterinarian Samantha Brooks. There are 18 known spelling errors in this gene that lead to white horses, she said. Like other horses with KIT mutations, the foal has some spots of brown along the spine – the product of cells that were waiting for a signal to migrate.

Some horses inherit a KIT mutation from a white parent, but in this case, the mutation is new and unique to this horse.

Until now, scientists weren't sure how common such de novo mutations are in our species. In a study published earlier this month in Science, Washington's Akey showed that we humans are riddled with them.

He and his colleagues took DNA from 2,440 people of both European and African descent and examined just the parts that hold the code for specific proteins. The result: "We all carry our own personal mutations and an even larger number of mutations that are extremely rare," he said.

Some of these may have no biological effects, but he suspects many have a subtle influence on risks for such diseases as Alzheimer's, multiple sclerosis, heart disease, diabetes, cancers, and mental illness.

It's not that we've stopped evolving, Akey said. But the winnowing hand of natural selection has gone easy on our species in recent centuries. Charles Darwin observed that natural selection works because each generation of plants and animals produces many more offspring than can possibly survive. The "struggle for existence," as Darwin described it, leaves just those best equipped to survive and reproduce.

Humans are still subject to evolution, said Akey, but we're experiencing a population explosion. New mutations are appearing much faster than natural selection can filter out the deleterious ones.

If the white foal's mutation is indeed in KIT, then it's dominant, meaning that if he became a sire, it would affect half of his offspring. How far he spreads his new mutation depends on whether his owners think he has a talent for racing. So far, the signs are good, said his owner, Peter Congilose. "He can turn on a dime. He's agile, he's quick. … I've never seen a horse that can move like this."

References: http://www.sciencemag.org/content/early/2012/05/21/science.1219240

Contact Faye Flam at 215-854-4977, [URL]fflam@phillynews.com;/[URL], or [URL]@fayeflam;/[URL] on Twitter. Read her blog at [URL]philly.com/evolution;.