700,000-Year-Old Horse Genome Shatters Record for Sequencing of Ancient DNA

By piecing together the genetic information locked inside a frozen, fossilized bone, scientists have deciphered the complete genome of an extinct prehistoric horse that roamed the Yukon more than 700,000 years ago. The work rewrites the evolutionary history of the horse andsmashes the previous record for the oldest complete genome ever sequenced. In doing so, itredefines how far back in time scientists can travel using DNA sequences as their guide.

Every time a cowboy throws a leg over the saddle and gallops off on his horse, hes riding on top of 4 million years of evolutionary history. But this history is mostly a mystery. We know surprisingly little about how natural selection and thousands of years of selective breeding by humans have shaped these animals on the genetic scale.

Horses were once considereda textbook example for the smooth transition of one species into another, a perfect illustration of Darwins theories. Ancient equine species dog-sized animals with five toes gradually evolved into towering, hooved thoroughbreds. Or so the story went. But with every fossil that was unearthed, a more tangled picture emerged.

Then DNA sequencing came along, allowingscientists to reconstruct how organisms change over time down to the resolution of single letters in the DNA code.

In the new study, a multinational team of scientistsled byLudovic Orlando and Eske Willerslev at the University of Copenhagen used whats become a common approach: comparing the DNA ofmodern species to DNA recovered from fossil remains, in this case a fossil bone fragment found near Thistle Creek, Canada. By pushing DNA sequencing technology to its limits, they were able to rewind the evolutionary clock back further than ever before.

The previous record for oldest genome was an 80,000-year-old ancient cousin of humanswhose genome was sequenced from a single finger bone found in Siberia. The Thistle Creek horse appears to be nearly ten times as old, which provided new challenges for the scientists. DNA sequencing technology is constantly improving, but the information that researchers get in the end is only as good as the DNA that they start with. And thats where scientists like Orlando are fighting a losing battle against nature.

Recent technological advances, several developed solely for this work, allowed the horse genome wranglers to read their DNA sequences with as little as a single molecule of starting material. And beefed up computing power meant they could rebuild genomes stretching billions of bases from chunks as small as 25 individual letters. It is a 12.2 billion-piece jigsaw puzzle, said Mike Bunce, a paleogeneticist at Murdoch University, who was not involved in the study.

Not only was the DNA heavily degraded, the bone itself had adopted a host of microbial residents, the tiny engines of decomposition, each full of their own DNA. The team again turned to powerful computer programs to pick out which sequences belonged to the horse and which belonged to the bacteria.

The final product of all this work was a complete rough draft sequence of the Thistle Creek horses genome.

In order to place the Thistle Creek Horse on the evolutionary timeline, the researchers compared its genome to those of a younger extinct species, several modern domestic horses, a donkey, and a wild Asian horse. The results of this comparison, reported today in Nature, push back the origin of theEquuslineage, which includes all living horses, zebras and donkeys, to a common ancestor living 4 million years ago.

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700,000-Year-Old Horse Genome Shatters Record for Sequencing of Ancient DNA