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Whoa, Nellie! Horse genome is revealed; equine genetics help answer a core chromosome question.

Scientists around the world are reading an entirely new type of Twilight saga--not a fictional account of vampires, but the real-life evolutionary story of horses that's encoded in the DNA of a gray mare. And the tale has plenty of plot twists researchers didn't see coming.

A mare named Twilight, who lives at Cornell University, gave her DNA to the Horse Genome Project, an international collaboration. The complete picture of the Thoroughbred's 2.5 billion to 2.7 billion DNA bases--the chemical building blocks that encode her genetic information--reveals that horses and humans share large blocks of DNA where genes are lined up in the same order, researchers involved in the sequencing effort report in the Nov. 6 Science.

Horses have about 90 inherited conditions--such as inflammatory diseases, infertility and muscle disorders--that also affect humans. Because the human and horse genomes are similar, knowing where disease genes are in the horse genome might make it easier to pinpoint the genes in people, says Kerstin Lindblad-Toh, a geneticist at Uppsala University in Sweden and the Broad Institute of MIT and Harvard University. Lindblad-Toh and Claire Wade, a geneticist and computational biologist at the University of Sydney, led the horse genome project.

Horses tend to have older versions of genes- closer to the form seen in the common ancestor of vertebrates--than those in humans or mice, so the horse genome "may be more indicative of where we came from," says David Haussler, a geneticist and computational biologist at the University of California, Santa Cruz.

Haussler and his colleagues have proposed sequencing more than 10,000 vertebrate genomes to put together a more detailed map of genetic changes that led to the modern forms of animals. The researchers detail their proposal online November 6 in the Journal of Heredity.

Already the horse genome has helped to answer at least one fundamental question in biology: What is needed for proper centromere function? Centromeres are stretches of DNA, often located near the centers of chromosomes, that are instrumental in the proper segregation of chromosomes during cell division. The centromere usually contains a core element surrounded by repetitive DNA sequences. Scientists know that the repetitive DNA helps stabilize the interaction of cellular machinery with the centromeres but haven't known the exact steps needed to build a centromere. Specifically, it has been unclear whether a core element could work without the surrounding repetitive sequences and vice versa.

On chromosome 11, horses have an evolutionarily young centromere, one that developed within the last few million years or so, the researchers report. The centromere is functional, but it isn't wrapped in a blanket of repetitive DNA, suggesting the repetitive elements aren't necessary for a centromere to function. "It's really solved the chicken-or-egg problem," says Lindblad-Toh.

Which doesn't mean the repetitive DNA isn't useful, says Wade. "It's like moving house," she says. "When you live somewhere for a long time, you accumulate a lot of stuff around you that makes you feel secure, but when you move, you clean house. This centromere has just moved." In time, the centromere on horse chromosome 11 will acquire repetitive sequences around it, making it more stable and settled, she says.

Analyses of the horse genome are also helping scientists trace the animal's evolutionary and domestic history and pin down the horse's relationship to other equines. About 3 million years ago, the genus Equus split into eight or nine different species, including horses (Equus caballus), zebras (Equuszebra) and donkeys (Equus africanus).

Horse Genome Project researchers mapped about 1 million locations in the horse genome with single letter variations in the DNA. Comparing the pattern of those spelling variations--known as SNPs--the scientists could reconstruct a family tree for horse breeds. Modern domestic horses are thought to have evolved from wild horses such as Przewalski's horse, a short, dun-colored equine with a stiff Mohawkstyle mane. Because the wild horse has an extra pair of chromosomes compared with modern domestic horses, the team was surprised to find that Przewalski's horse had no SNPs of its own. All of the spelling differences detected in Przewalski's were also found in domestic horse breeds, Wade says.

Either ancestral horses had extra chromosomes, as Przewalski's horse does, which later fused to form a single chromosome in the domestic horse, or ancestral horses had a big, domestic-looking chromosome that later broke to make the Przewalski's extra chromosomes, Wade says.

Donkeys, on the other hand, have unique variations that place Equus africanus in a clearly different group from horses. The result could mean that domestic horses and Przewalski's horses interbred after their subspecies split or that Przewalski's horses actually derived from domestic horses.

Also recorded in the horse DNA is the history of horse domestication. Analysis of the genome confirms previous genetic (SN: 2/10/01, p. 95) and archaeological evidence that there was not a single domestication event with a small number of horses that served as a founding group.

Instead, "it's quite easy to imagine that we [humans] may have taken all the horses from the wild to use for our own purposes," Wade says. Many different groups of humans may have collected horses from the wild. For example, archaeological data published earlier this year suggest people were milking horses 5,000 years ago (SN: 3/28/09, p. 15). "Basically, they were useful so we took them all," she says.

Genetic data suggest that a few stallions and many mares have contributed their DNA to the modern domestic horse lineage. Thus it appears that humans preserved the herd structure horses follow in the wild--a stallion with a harem of mares--so horses didn't balk at domestication, Wade speculates. "It really wasn't a big impact on their social structure so they didn't mind too much."

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Article Details
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Author:Saey, Tina Hesman
Publication:Science News
Geographic Code:1USA
Date:Dec 5, 2009
Previous Article:The (-est).
Next Article:Back story: whole genomes: about 5,000 down, 10,000-plus to go.

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