Wednesday, June 26, 2013

700,000 Year Old Horse's DNA Sequenced

A horse is still recognized as a horse, from DNA 700,000 years old.

From Scientific American Online:

Horse Fossil Yields Astonishingly Old Genome—Are Similarly Ancient Human Genomes Next?
Researchers have recovered DNA from a nearly 700,000-year-old horse fossil and assembled a draft of the animal’s genome from it. It is the oldest complete genome to date by a long shot–hundreds of thousands of years older than the previous record holder, which came from an archaic human that lived around 80,000 years ago. The genome elucidates the evolution of modern horses and their relatives, and raises the question of whether scientists might someday be able to obtain similarly ancient genomes of human ancestors.

Ludovic Orlando of the University of Copenhagen and his colleagues extracted the DNA from a foot bone found at the site of Thistle Creek in Canada’s Yukon Territory in permafrost dating to between 560,000 and 780,000 years ago, which falls within the so-called early Middle Pleistocene time period. They then mapped the fragments of DNA they obtained against the genome of a modern horse to piece together a draft of the ancient horse’s genome.

Comparing that sequence to the genomes of a 43,000-year-old horse, a donkey, five modern domestic horses and a modern Przewalski’s horse (a type of wild horse native to Mongolia), the researchers were able to gain insights into some key aspects of horse evolution. Their findings indicate that the last common ancestor of the members of the genus Equus—which includes modern horses, donkeys, asses and zebras, along with their extinct relatives–lived some 4 million to 4.5 million years ago, double the estimate suggested by the oldest unequivocal Equus fossils. The results also allowed the team to chart the demographic history of horses over the past two million years, revealing how the population waxed and waned as climate shifted and grasslands expanded and contracted. In addition, the researchers identified several genome regions in modern horses that seem to have been targeted by natural selection acting to promote advantageous gene variants related to immunity and olfaction, as well as a number of genome regions that may have undergone selection related to domestication. A report detailing the study will be published in the June 27 Nature. (Scientific American is part of Nature Publishing Group.)

This is a pretty exciting development (so exciting, in fact, that I’m interrupting my vacation to write about it). And I can’t help but think back, as I do whenever a new ancient DNA story breaks, to the first time I ever reported on DNA from deep time. The year was 1997. Researchers had just announced that they had sequenced DNA from a 40,000-year-old Neandertal fossil. Specifically they had sequenced DNA from mitochondria—the cell’s energy-producing organelles, which contain their own DNA that is passed on along the maternal line.

The Neandertal mitochondrial genome was a huge breakthrough—and it seemed to settle a long-running debate over Neandertals and the origin of anatomically modern Homo sapiens. But mitochondrial DNA represents only a tiny fraction of an individual’s genetic information; the real action is in the DNA that resides in the cell’s nucleus—the nuclear genome. The scientists I spoke to back then—geneticists and paleontologists—longed for a nuclear genome from a Neandertal. But they were quite certain that they would never ever get one. Mitochondrial DNA is far more abundant than nuclear DNA, because a cell can contain hundreds of mitochondria, whereas it has just one nucleus. Thus the chances of finding nuclear DNA that has survived the ravages of time is far, far lower than those of obtaining mitochondrial DNA—itself a rarity.

And yet. Fast forward to 2010 and the impossible dream was realized: a draft sequence of a nuclear genome of a Neandertal. More recently the sequencing of nuclear DNA retrieved from an enigmatic finger bone from Denisova Cave in Siberia has revealed a previously unknown kind of human. And scientists have obtained an astonishingly complete Neandertal genome from the same cave site. These ancient nuclear genomes paint a rather different picture of archaic-modern human relations than the early mitochondrial DNA work did, and are providing a wealth of fascinating insights into our own evolution and that of our relatively recently extinct cousins.

This fantastically old horse genome got me thinking about the possibility of recovering DNA from comparably ancient human relatives—ones who roamed the earth long before the Neandertals and the Denisovans. If scientists had such data, what would they try to learn from it? When I asked paleoanthropologist John Hawks of the University of Wisconsin this question, he had this to say:
“Right now the Denisovan and Neandertal genomes have raised a new scenario of population structure for Middle Pleistocene people. They show us that earlier hominins in Eurasia were largely supplanted, possibly with some mixture, by a dispersal of Neandertal and Denisovan ancestors. What was that pre-Neandertal population like? Did it have its own unique events shaping its evolution? How many times did large-scale dispersals of human populations sweep across the Old World? And what happened to African ancestors during this key Middle Pleistocene time period?”

Now, lest we get ahead of ourselves, it must be noted that the horse fossil was found in permafrost, which no doubt contributed to the preservation of the DNA. So will scientists have to find a Middle Pleistocene human on ice (or ice-cold soil) to have any hope of getting a genome out of it? Not necessarily. The Denisova specimens weren’t preserved in permafrost and their ancient DNA is first class. Still, they are far younger than the horse fossil. But according to ancient DNA expert Hendrik Poinar of McMaster University in Canada, the key to DNA preservation is dry conditions. “While cold and dry is best, warm and dry will still work,” he explains.

Poinar additionally noted that he is certain that researchers will eventually recover genomes even older than this 700,000-year-old (give or take) one. Which brings me to my final thought. When I learned of the horse genome, the first thing I thought was: what does this mean for Australopithecus sediba, the two million-year-old fossil species unearthed in at the site of Malapa in South Africa a few years ago. It has been held up as a candidate for the long-sought ancestor of our genus, Homo. These fossils are exquisitely preserved and may even contain organic material. Some of the remains are completely encased in rock, visible only with computed tomography and other imaging techniques. Might scientist be able to extract DNA from these fossils—and might that DNA be sufficiently well preserved to yield a genome? “I think DNA from Malapa is very possible and an exciting prospect,” Poinar says.

In fact, efforts are already under way to recover DNA from the A. sediba fossils, “We are in the process of looking and there are specimens presently being investigated,” says paleoanthropologist Lee Berger of the University of the Witwatersrand, who is leading the recovery and analysis of the fossils from Malapa. “It is of course unlikely in a [two million-year-old] fossil,” he notes, “nevertheless, Malapa has as good a chance as anywhere if the impossible is going to prove possible.”

I’m going to resume my vacation now. But I’ll be daydreaming about genomes from our long-vanished cousins. The future of ancient DNA research has never looked brighter.

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