Category Archives: Genome

Genetic material suitable for sequencing could persist for as many as one million years, predict scientists.

A Przewalskis horse, which represents the last surviving line of wild horses, in Khomyntal, Western Mongolia.

Small pieces of a horses foot bone that were frozen for approximately 700,000 years in the Yukon Territory of Canada have yielded the oldest genome sequence of any species to date.

Scientists unearthed the bone fragments from the Artic permafrost in 2003 and dated the fossils to be between 560,000 - 780,000 years old. Using mass spectroscopy, they found that collagen and other proteins had survived since the Middle Pleistocene and so decided to see if DNA had also endured.

It had, and the resulting genome is nearly ten times older than any DNA previously sequenced, thus breaking the time barrier for the age of DNA viable for such analysis, said study author Eske Willerslev of the University of Copenhagen at a press conference in Helsinki on Wednesday.

Two pieces of the 700,000 year-old horse foot bone, just before scientists extracted the ancient DNA.

While the cold and dry conditions of the permafrost helped keep the DNA intact, the authors also perfected techniques for handling and analyzining the ancient DNA: reports Nature:

They also combined DNA sequencing techniques to get maximum DNA coverage using routine next-generation sequencing with single-molecule sequencing in which a machine directly reads the DNA without the need to amplify it up which can lose some DNA sequences.

The researchers predict that future ancient DNA studies could go even further back in time most likely up to a million years said Ludovic Orlando, a scientist at the University of Copenhagen and co-author on the study. Such a deep look into the evolutionary past obviously offers great perspective as to the level of detail with which we could reconstruct our own origins and the evolutionary history of almost every single species living on the planet, he said.

The study was published in Nature in Wednesday.

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700,000-Year-Old Horse Genome Pushes Limits of DNA Survival

Two pieces of the 700,000 year-old horse metapodial bone, just before DNA extraction. Image courtesy of Ludovic Orlando

An ancient horse jaw found in the permafrost in Canadas remote Yukon territory has caused paleogeneticists to recalibrate their entire understanding of the history of horses. Traces of collagen within the bone matrix contained enough intact DNA to sequence the entire genome, making it the oldest complete genome to date.

The fossilized equine lived during the Middle Pleistocene, 560 to 780 thousand years ago. This makes its genome the oldest of any species ever sequenced, by a long shot. In fact, this horse genome is about six times older than the current record-holdera polar/brown bear mix with only 110 to 130 thousand years under its belt. Its a cub by comparison.

With the ancient horses genome in hand, the researchers wanted to trace the evolution of this earlyEquusspecimen tocontemporary horses. The line-up of comparative species included a horse from the Late Pleistocene (43 thousand years old), a modern Przewalskis horse (thought to be the lastline of wild horses), and five modern breeds (Arabian, Icelandic, Norwegian fjord, Standardbred and Thoroughbred). Just for kicks, the researchers also sequenced a donkey.

DNA overlap showed that the ancient horse gave rise to all modern wild and domestic horses as well as donkeys and zebras. Based on the genetic variation between these species, and the rate at which such changes could have feasibly occurred, the scientists determined that the Equus lineage originated 4 to 4.5 millions years agoextending the horse lineage twice as far as previously thought.

Przewalski horses in Khomyntal, Western Mongolia, in one of the three reintroduction sites. The horses were imported in 2004 from Le Villaret, France. Image courtesy of Claudia Feh, Association pour le cheval de Przewalski.

Researchers were also able use the data to pin down when wild and domestic horse populations diverged, some38 to 72 thousand years ago. Since this time, the genes show that domestic horses have been continuously selected for their hearty immune systems and a strong sense of smell.

The finding has implications for wild horses as well: it confirms that Przewalskis horses are indeed the last surviving species of wild horse, since they split from the common ancestor before the differentiation ofdomestic breeds. Przewalskis horses were listed as extinct in the wild in 1996 but have since been reintroduced to the Mongolian steppe, and this sequencing suggests that individuals have enough genetic variation to warrant continued conservation efforts.

The researchers also found that horse populations peaked and plummeted multiple times in the past two million years in alignment with periods of extreme climate change, according to the study published in Nature today.

Sequencing the oldest genome provides new insights on horse history, but the technique will have implications for all sorts of ancient species. The study shows that tiny bits of ancient DNA once thought too old or small to use can actually still be sequenced. Buried in the upper layers of the Earths crust,snippets of DNA as short as 25 basepairs in length may be able to survive more than a million years. So giddyup, paleogenetecists!

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Oldest Complete Genome Shows Evolution of Ancient Horses

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A prototype for a hardware display of a genome sequence as a moving series of coloured LEDs. The LED array can be extended indefinitely with no extra program...

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Contact: Hilary Glover hilary.glover@biomedcentral.com 44-020-319-22370 BioMed Central

Focusing on parts rather than the whole, when it comes to genome sequencing, might be extremely useful, finds research in BioMed Central's open access journal Genome Medicine. The research compares several sequencing technologies in the same individual with Charcot-Marie-Tooth disease (CMT), and shows that sequencing the coding regions alone at high depth of coverage can identify the genetic variation behind this disease, and was also able to resolve previous ambiguities.

Next generation sequencing for understanding human DNA variation and genetic disorders is advancing in leaps and bounds. Whole genome sequencing reads all of an individual's DNA, whereas exome sequencing captures only the parts of the DNA which code for proteins. Exome sequencing is faster and cheaper, but concerns have previously been raised that it misses important information.

A team from Baylor College of Medicine led by Prof. James Lupski and Prof. Richard Gibbs compared several different exome and whole genome sequencing technologies on DNA from the same person with CMT. Prof. Jim Lupski explained, "Both methods were able to find the same 12 variants which affect cellular response to specific drugs such as betablockers, warfarin and the anti-cancer drug paclitaxel, and identify novel CMT-associated mutations in SH3TC2 that encodes for a protein with a role in peripheral nerve myelination."

Exome sequencing had fewer false positives, and a greater sensitivity due to the higher coverage achieved when focusing only in a small fraction of the genome. Consequently it was able to correctly identify nucleotides which were ambiguous when using whole genome sequencing at lower coverage, and so clarify whether they were associated with CMT or not.

Prof. Richard Gibbs commented, "The higher coverage afforded by focusing on the exome at approximately 120x for clinical exomes allows greater precision of exome sequencing making this a superior approach, rather than a shortcut, to find which people might respond to a particular therapy or to define who has a specific disease."

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Whole genome or exome sequencing: An individual insight

Scientists will map the genome of Australia's greatest racehorse, Phar Lap, hoping to unlock the DNA secrets behind the champion's pace and staying power, a research team said Wednesday.

The giant New Zealand-born chestnut became an icon in Australia during the Great Depression, winning 37 of his 51 races, including one Melbourne Cup in 1930 and two Cox Plates in 1930 and 1931.

Australian scientists were in 2008 able to prove with high-tech testing of Phar Lap's hair that the legendary gelding was poisoned with arsenic in the United States in 1932.

And researchers are again looking to dissect the champion's genetic material, with a University of Sydney team announcing plans to sequence Phar Lap's genome from a tooth fragment.

"We are doing this out of scientific curiosity and all our data will be made publicly available," said lead researcher Natasha Hamilton.

"The DNA sequence will tell us if Phar Lap's genetic make-up looks like star racehorses of today, including whether he is a sprinter or a stayer -- genetically better suited to running long distances."

Hamilton said it was believed to be the first time a Southern Hemisphere thoroughbred's entire genome had been sequenced, in contrast to Europe where such research was popular.

"DNA analysis has been performed on notable horses such as Eclipse, racing's first superstar and an ancestor of 95 percent of today's thoroughbreds, and Hyperion, a popular sire from the 1930-50s who is found in numerous pedigrees," she said of the European studies.

The DNA will be extracted from a 60 milligram tooth fragment from Phar Lap's skeleton, which is housed at Te Papa Tongarewa, the Museum of New Zealand.

The researchers warned that the boiling of the skeleton in a corrosive solution during the preservation process in the 1930s meant the DNA was likely to have been fragmented -- not an issue for sequencing efforts but a dampener on cloning hopes.

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Australians to sequence Phar Lap genome

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

In the movie Jurassic Park dinosaurs were cloned from old DNA genome that had miraculously survived from millions of years ago, In practice this is not very likely. The oldest genome so far from a prehistoric creature has been sequenced by an international team, led by scientists from the Natural History Museum of Denmark (University of Copenhagen). The team, which included Dr Jakob Vinther of the University of Bristol, sequenced and analyzed short pieces of DNA molecules preserved in bone-remnants from a horse frozen for the last 700,000 years in the permafrost of Yukon, Canada.

By tracking the genomic changes that transformed prehistoric wild horses into the present domestic breeds, the researchers have revealed the genetic make-up of modern horses with unprecedented detail. Their findings are published today in Nature.

The horse genome was first sequenced in 2007. The Horse Genome Project mapped 2.7 billion DNA base pairs. The horse genome is larger than the dog genome, but smaller than the human genome or the bovine genome. It encompasses 31 autosomes and two sex chromosomes.

DNA molecules can survive in fossils well after an organism dies, but not as whole chromosomes but as short pieces that could be assembled back together, like a puzzle. Sometimes enough molecules survive so that the full genome sequence of an extinct species could be resurrected and over the past few years, the full genome sequence of a few ancient humans and archaic hominid has been characterized but so far, none have been dated back more than 70,000 years. Now Dr Ludovic Orlando and Professor Eske Willerslev from Copenhagen's Center for GeoGenetics and colleagues have beaten this DNA-record by about 10 times to 700.000 years.

Sequencing the first genome from the Middle Pleistocene was by no means straightforward and involved collaboration between researchers from Denmark, China, Canada, the USA, Switzerland, the UK, Norway, France, Sweden and Saudi Arabia.

Dr Vinther's contribution to the study involved looking at the amino acid composition of the bone with a Time of Flight Secondary Ion Mass Spectroscope (TOF-SIMS). This analysis revealed the presence of abundant secondary ions characteristic of amino-acid peptides, particularly glycine, proline and alanine. These amino acids are characteristic of collagen which suggested that proteins had survived in situ.

Dr Orlando said: "We first got excited when we detected the signature of amino-acids that suggested proteins had survived. We got more excited when we proved able to directly sequence collagen peptides. When we detected blood proteins, it really started looking promising because those are barely preserved. At that stage, it could well be that ancient DNA could also be preserved."

Using Helicos true Single DNA Molecule Sequencing, the researchers managed to identify molecular preservation niches in the bone and experimental conditions that enabled finishing the full genome sequence.

Sequencing the genome allowed the scientists to track major genomic changes over the last 700,000 years of evolution of the horse lineage. By comparing the genome in the 700,000-year-old horse with the genome of a 43,000-year-old horse, six present day horses and the donkey, they found that the last common ancestor of all modern equids was living about 4.0-4.5 million years ago. Therefore, the evolutionary radiation underlying the origin of horses, donkeys and zebras reaches back in time twice as long as previously thought.

The evolution of the horse pertains to the descent of the modern horse from the small, dog-sized, forest-dwelling Eohippus over a period of some 50 million years. Paleozoologists have been able to piece together a more complete picture of the modern horse's evolutionary lineage than that of any other animal.

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Horse Genome

The genome of a horse that lived 700,000 years ago in Canadas Yukon Territory suggests the common ancestor for modern horses, zebras, and donkeys dates to 4 million years ago.

The DNA discovered from the ancient horse is 10 times as old as any DNA retrieved so far, suggesting it may be possible to get genetic information from animals that lived as long as 1 million years ago, according to a study released yesterday in the journal Nature.

The finding is remarkable because DNA, the hereditary material in almost all organisms, generally starts to fragment after an organisms death, the researchers said. The group made its discovery by matching the genetic material of the horse found in Canada against DNA sequenced from a horse that lived 43,000 years ago; a Przewalski horse, thought to be the last wild horse; five modern domesticated breeds; and a donkey. The finding also means that DNA pieces retrieved from old samples may also have information about how the current world evolved, the study authors wrote.

Our study has pushed the timeframe of paleogenomics back by almost an order of magnitude, said the authors, led by Ludovic Orlando, Aurelien Ginolhac, and Guojie Zhang, of the universities of Copenhagen and BGI-Shenzhen.

The DNA was partly preserved by the cold environment, the authors wrote.

To contact the reporter on this story: Elizabeth Lopatto in San Francisco at elopatto@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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Genome of Horse That Galloped 700,000 Years Ago Sequenced

Scientists have reconstructed the genome of a horse that lived some 700,000-years-ago, mapping out the evolutionary history of the modern horse.

Researchers have sequenced the genome of a horse that lived some 700,000 years ago the oldest genome ever sequenced making it possible to reconstruct an evolutionary narrative of the modern horse, whose journey through history has been intimately bound to our own.

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According to a study published in the current issue of the scientific journal, Nature, the genome, of an ancient horse that lived in what is now Canadas Yukon, is about 10 times older than the previous oldest genome, of a human that lived about 70,000 years ago. That means the hindsight of paleogenomics has been dialed backwards some 630,000 years from where it was, offering up the extraordinary possibility that scientists may be able to reproduce our prehistoric record in greater detail than ever before, tracing not just the evolution of horses but tantalizingly of humans.

"We have beaten the time barrier, said evolutionary biologist Ludovic Orlando of the University of Copenhagen, a lead author of the study, in a statement.All of a sudden, you have access to many more extinct species than you could have ever dreamed of sequencing before.

Discovered in 2003, the ancient horse bones were bound in the worlds oldest known permafrost at Canadas remote Thistle Creek site. A multinational team of scientists, headed by Dr. Orlando and Eske Willerslev, also of the University of Copenhagen, then extracted DNA from one of the animals toes after determining that the bone was a promising candidate to still have viable DNA: had the DNA not been kept cold and dry, it would have not survived those more than half-million years.

Sequencing DNA as fantastically old as that of the ice-encased horse is tough work, and the successful mapping of its genome is a testament to just how far sequencing technology has come, since the first genome, of a virus that infects bacteria, was sequenced in 1976.

The scientists mulled over fragmented and deteriorating DNA, building from disjointed strings of just 25 individual letters a complex genome that is billions of bases long. And since the DNA had accumulated bacteria tenants during its long, icy repose, scientists also had to ferret out which sequences belonged to the horse, and which to the bacteria.

That complex sequencing needed fact checking. To confirm the horses age, scientists compared it to younger horses genomes, sequencing a DNA sample from the frozen bones of a horse some 43,000-years-old, as well as samples from a donkey, five modern domestic horses, and a wild horse native to Mongolia. They say they are now confident that the horse is a staggering 700,000 years old.

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Straight from the horse's toe: The world's oldest genome

Researchers have reconstructed an ancient genome from a horse that has become the oldest specimen ever found.

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Researchers have reconstructed a genome that is 10 times as old as ones discovered in the past.

The discovery has led scientists to believe that DNA reconstruction for animals up to one million years old is possible. The ancient genome, which is from a horse, is more than 700,000 years old. If it is accepted as a specimen, it would extend the reach of paleogenomics, or the study of genomes reconstructed from fossil bones, tenfold.

Before this discovery, the oldest recovered DNA belonged to a Denisovan human that lived 70,000 years ago.

The genome increases the understanding of evolution as well. Scientists compared the genome to modern horses, zebras and donkeys -- all part of genus Equus -- and found that the genus arose about 4 million years ago, twice as long ago as had been thought.

Horses have long been used as a classic illustration of one of Darwin's theories: Ancient equine species, which were five-toed animals the side of dogs, evolved over time into the hooved horses we know today. But as older genomes have been found, scientists have discovered the evolution is not that clean-cut.

The DNA came from a frozen, fossilized bone from an extinct prehistoric horse in the Yukon. Technology developed for genome projects enabled scientists to use the bone, which was covered in microbes -- each with its own set of DNA -- to determine which of the DNA belonged to the horse.

Having such technology available has opened the door to using genomes that were previously thought to be too damaged to use, and to fill in the gaps in existing research. Danish scientists used the horse's genome to predict the horse's gradual change in size over time, and the potential for research on how the climate has affected them and other animals over time.

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Scientists reconstruct 700,000-year-old genome, breaking record for oldest sequenced DNA