In a first for science, a snippet of genetic code from long-gone species is inserted in mice and shown to work
Tasmanian tigers are back. Sort of. A small bit of the extinct marsupial’s DNA is alive and well in the cells of some genetically engineered mice.
Scientists have produced proteins from mammoth and Neandertal genes in cells, but the new study, appearing in the May 19 PLoS ONE, is the first to examine the activity of an extinct piece of DNA in a whole animal.
Scientists from the University of Melbourne in Australia and the University of Texas M. D. Anderson Cancer Center in Houston extracted DNA from alcohol-preserved specimens of the Tasmanian tiger, also known as the thylacine. The researchers then inserted into mice a piece of thylacine DNA that controls production of a collagen gene. The thylacine DNA worked, switching on a marker gene in cartilage-producing cells in a mouse embryo, essentially resurrecting a bit of the extinct animal.
But don’t expect mice to transform into the doglike marsupials, or for scientists to reanimate thylacines through cloning.
“This technology can tell us interesting things about thylacines bit by bit,” says Robin Lovell-Badge, a developmental geneticist at the Medical Research Council’s National Institute for Medical Research in Mill Hill, England. “As far as bringing back thylacines, this is not going to be able to do that.”
“I love the idea,” Lovell-Badge says of somehow engineering mice into thylacines, “but no, not like this.”
As for the cloning the extinct animal, it’s not likely to happen, says Carles Lalueza-Fox, a paleogeneticist at the University of Barcelona in Spain.
“It’s impossible to clone extinct animals like some people claim they will do with frozen mammoths. That’s fantasy, not science,” Lalueza-Fox says.
But the researchers involved in the new study never intended to bring back the thylacine, just to learn something more about its biology and perhaps add to the evolutionary history books. This type of study could teach biologists how species use their genes to create the tremendous diversity in body shapes and sizes.
We were very interested in finding out a little bit more about this iconic Australian carnivore, especially since we humans were responsible for its extinction,” says Marilyn Renfree, a reproductive and developmental biologist at the University of Melbourne and one of the authors of the new study. “This study has given us proof that one can ask these sorts of questions and get answers.”
To prove that DNA from an extinct species can still work, the team chose a regulatory element, called an enhancer, which regulates the Col2a1 gene and has been conserved throughout evolution in animals with backbones, says Andrew Pask, a molecular biologist at the University of Melbourne.
Enhancers serve as landing pads for proteins that turn genes on. Only specific proteins are granted landing privileges and only at prescribed times of development in particular types of cells. The Col2a1 enhancer turns the gene on only in chondrocytes — cartilage-producing cells— in mouse embryos. The enhancer works similarly in birds and mammals, so the researchers hoped that the thylacine DNA would also produce a familiar pattern of gene activity.
That hope was fulfilled. Mouse embryos engineered with the thylacine enhancer turned on production of a marker that the researchers use to track gene activity. The enhancer worked only in chondrocytes.
The new study is the first using extinct DNA that does not encode a protein but controls how genes are turned on and off. In previous studies, mammoth and Neandertal genes were used to produce proteins in cell culture, not in living animals.
“This is the next logical step to try to bring ancient DNA into an animal or biological system,” says Stephen Schuster, a genomicist at Pennsylvania State University in University Park. Researchers might use the technique to find enhancers and other regulatory elements that could make a chicken look like a dinosaur or an elephant look like a mammoth, he said. But such methods, even if they could achieve such dramatic results, would not bring back dodos, dinosaurs and mammoths.
“If you had a very hairy African elephant, that would be a first step to looking like a mammoth, but of course it wouldn’t be a mammoth. It would just be a weird-looking elephant,” Schuster says.
Even though the thylacine enhancer seems to work the same way as the mouse enhancer does, that’s no guarantee that the researchers have the correct answer to how thylacine DNA functions. Mice and marsupials are so different that sometimes enhancers might misbehave when placed in a mouse, giving researchers the wrong impression about how such bits of DNA worked in extinct animals, says Lalueza-Fox.
“To use an animal model is always difficult, but to use an eutherian [placental] animal model for a marsupial is really quite risky,” he says.
Other researchers concede that genetically engineered mice might sometimes yield misleading data, but see no alternative way to study gene function from extinct species.
“The problem with extinct animals is that they’re extinct,” says Michael Hofreiter, an evolutionary biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “Cell cultures or the mouse models are the only possibility we have of learning how non-coding DNA worked in extinct animals. The question is not whether this is the best way forward — it’s the only way forward.”
These kinds of studies are necessary to understand where and when genes are turned on and off in the bodies of extinct animals. That information may be encoded in the DNA of the animals, but predicting how variations between two species changes gene function is not well understood. Such studies could show how the thylacine got its stripes or what made mammoths so woolly.
Even armed with information about how thylacine genes worked, the technology used in the study is unlikely to bring back the Tasmanian tiger, Hofreiter says. In order to re-create the thylacine from a mouse using this technique, researchers would have to replace the mouse genome bit by bit, using about 10 million short pieces of DNA. That would take years and be would be extremely costly, not to mention that at some point, a chimeric animal (part-mouse, part-thylacine) would be unlikely to survive, he says.
Schuster favors a bigger, bolder approach to re-creating extinct animals, one that admittedly is still science fiction. He would stitch together entire chromosomes from an extinct animal and replace a host animal’s chromosomes with the synthetic creations. In that way, an elephant’s genetic material might be replaced with mammoth DNA, essentially reincarnating the Ice Age icon.
Scientists are only just beginning to learn how to create whole chromosomes.
“With DNA we’re very good at reading information, but we’re not good at writing. It’s like we’ve got a computer, but we don’t have a printer,” Schuster says.
Thylacines have no living counterpart. Their closest living relatives are Tasmanian devils, but no one has ever genetically engineered a Tasmanian devil, making it an unlikely host should the technology to clone extinct animals become available.
Re-creating extinct organisms captures the imagination, Schuster says, but it is far easier and less expensive to protect the endangered animals still living on Earth.
Thursday, May 22, 2008
Reviving extinct DNA
In a first for science, a snippet of genetic code from long-gone species is inserted in mice and shown to work
Tasmanian tigers are back. Sort of. A small bit of the extinct marsupial’s DNA is alive and well in the cells of some genetically engineered mice.
Scientists have produced proteins from mammoth and Neandertal genes in cells, but the new study, appearing in the May 19 PLoS ONE, is the first to examine the activity of an extinct piece of DNA in a whole animal.
Scientists from the University of Melbourne in Australia and the University of Texas M. D. Anderson Cancer Center in Houston extracted DNA from alcohol-preserved specimens of the Tasmanian tiger, also known as the thylacine. The researchers then inserted into mice a piece of thylacine DNA that controls production of a collagen gene. The thylacine DNA worked, switching on a marker gene in cartilage-producing cells in a mouse embryo, essentially resurrecting a bit of the extinct animal.
But don’t expect mice to transform into the doglike marsupials, or for scientists to reanimate thylacines through cloning.
“This technology can tell us interesting things about thylacines bit by bit,” says Robin Lovell-Badge, a developmental geneticist at the Medical Research Council’s National Institute for Medical Research in Mill Hill, England. “As far as bringing back thylacines, this is not going to be able to do that.”
“I love the idea,” Lovell-Badge says of somehow engineering mice into thylacines, “but no, not like this.”
As for the cloning the extinct animal, it’s not likely to happen, says Carles Lalueza-Fox, a paleogeneticist at the University of Barcelona in Spain.
“It’s impossible to clone extinct animals like some people claim they will do with frozen mammoths. That’s fantasy, not science,” Lalueza-Fox says.
But the researchers involved in the new study never intended to bring back the thylacine, just to learn something more about its biology and perhaps add to the evolutionary history books. This type of study could teach biologists how species use their genes to create the tremendous diversity in body shapes and sizes.
We were very interested in finding out a little bit more about this iconic Australian carnivore, especially since we humans were responsible for its extinction,” says Marilyn Renfree, a reproductive and developmental biologist at the University of Melbourne and one of the authors of the new study. “This study has given us proof that one can ask these sorts of questions and get answers.”
To prove that DNA from an extinct species can still work, the team chose a regulatory element, called an enhancer, which regulates the Col2a1 gene and has been conserved throughout evolution in animals with backbones, says Andrew Pask, a molecular biologist at the University of Melbourne.
Enhancers serve as landing pads for proteins that turn genes on. Only specific proteins are granted landing privileges and only at prescribed times of development in particular types of cells. The Col2a1 enhancer turns the gene on only in chondrocytes — cartilage-producing cells— in mouse embryos. The enhancer works similarly in birds and mammals, so the researchers hoped that the thylacine DNA would also produce a familiar pattern of gene activity.
That hope was fulfilled. Mouse embryos engineered with the thylacine enhancer turned on production of a marker that the researchers use to track gene activity. The enhancer worked only in chondrocytes.
The new study is the first using extinct DNA that does not encode a protein but controls how genes are turned on and off. In previous studies, mammoth and Neandertal genes were used to produce proteins in cell culture, not in living animals.
“This is the next logical step to try to bring ancient DNA into an animal or biological system,” says Stephen Schuster, a genomicist at Pennsylvania State University in University Park. Researchers might use the technique to find enhancers and other regulatory elements that could make a chicken look like a dinosaur or an elephant look like a mammoth, he said. But such methods, even if they could achieve such dramatic results, would not bring back dodos, dinosaurs and mammoths.
“If you had a very hairy African elephant, that would be a first step to looking like a mammoth, but of course it wouldn’t be a mammoth. It would just be a weird-looking elephant,” Schuster says.
Even though the thylacine enhancer seems to work the same way as the mouse enhancer does, that’s no guarantee that the researchers have the correct answer to how thylacine DNA functions. Mice and marsupials are so different that sometimes enhancers might misbehave when placed in a mouse, giving researchers the wrong impression about how such bits of DNA worked in extinct animals, says Lalueza-Fox.
“To use an animal model is always difficult, but to use an eutherian [placental] animal model for a marsupial is really quite risky,” he says.
Other researchers concede that genetically engineered mice might sometimes yield misleading data, but see no alternative way to study gene function from extinct species.
“The problem with extinct animals is that they’re extinct,” says Michael Hofreiter, an evolutionary biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “Cell cultures or the mouse models are the only possibility we have of learning how non-coding DNA worked in extinct animals. The question is not whether this is the best way forward — it’s the only way forward.”
These kinds of studies are necessary to understand where and when genes are turned on and off in the bodies of extinct animals. That information may be encoded in the DNA of the animals, but predicting how variations between two species changes gene function is not well understood. Such studies could show how the thylacine got its stripes or what made mammoths so woolly.
Even armed with information about how thylacine genes worked, the technology used in the study is unlikely to bring back the Tasmanian tiger, Hofreiter says. In order to re-create the thylacine from a mouse using this technique, researchers would have to replace the mouse genome bit by bit, using about 10 million short pieces of DNA. That would take years and be would be extremely costly, not to mention that at some point, a chimeric animal (part-mouse, part-thylacine) would be unlikely to survive, he says.
Schuster favors a bigger, bolder approach to re-creating extinct animals, one that admittedly is still science fiction. He would stitch together entire chromosomes from an extinct animal and replace a host animal’s chromosomes with the synthetic creations. In that way, an elephant’s genetic material might be replaced with mammoth DNA, essentially reincarnating the Ice Age icon.
Scientists are only just beginning to learn how to create whole chromosomes.
“With DNA we’re very good at reading information, but we’re not good at writing. It’s like we’ve got a computer, but we don’t have a printer,” Schuster says.
Thylacines have no living counterpart. Their closest living relatives are Tasmanian devils, but no one has ever genetically engineered a Tasmanian devil, making it an unlikely host should the technology to clone extinct animals become available.
Re-creating extinct organisms captures the imagination, Schuster says, but it is far easier and less expensive to protect the endangered animals still living on Earth.
Tasmanian tigers are back. Sort of. A small bit of the extinct marsupial’s DNA is alive and well in the cells of some genetically engineered mice.
Scientists have produced proteins from mammoth and Neandertal genes in cells, but the new study, appearing in the May 19 PLoS ONE, is the first to examine the activity of an extinct piece of DNA in a whole animal.
Scientists from the University of Melbourne in Australia and the University of Texas M. D. Anderson Cancer Center in Houston extracted DNA from alcohol-preserved specimens of the Tasmanian tiger, also known as the thylacine. The researchers then inserted into mice a piece of thylacine DNA that controls production of a collagen gene. The thylacine DNA worked, switching on a marker gene in cartilage-producing cells in a mouse embryo, essentially resurrecting a bit of the extinct animal.
But don’t expect mice to transform into the doglike marsupials, or for scientists to reanimate thylacines through cloning.
“This technology can tell us interesting things about thylacines bit by bit,” says Robin Lovell-Badge, a developmental geneticist at the Medical Research Council’s National Institute for Medical Research in Mill Hill, England. “As far as bringing back thylacines, this is not going to be able to do that.”
“I love the idea,” Lovell-Badge says of somehow engineering mice into thylacines, “but no, not like this.”
As for the cloning the extinct animal, it’s not likely to happen, says Carles Lalueza-Fox, a paleogeneticist at the University of Barcelona in Spain.
“It’s impossible to clone extinct animals like some people claim they will do with frozen mammoths. That’s fantasy, not science,” Lalueza-Fox says.
But the researchers involved in the new study never intended to bring back the thylacine, just to learn something more about its biology and perhaps add to the evolutionary history books. This type of study could teach biologists how species use their genes to create the tremendous diversity in body shapes and sizes.
We were very interested in finding out a little bit more about this iconic Australian carnivore, especially since we humans were responsible for its extinction,” says Marilyn Renfree, a reproductive and developmental biologist at the University of Melbourne and one of the authors of the new study. “This study has given us proof that one can ask these sorts of questions and get answers.”
To prove that DNA from an extinct species can still work, the team chose a regulatory element, called an enhancer, which regulates the Col2a1 gene and has been conserved throughout evolution in animals with backbones, says Andrew Pask, a molecular biologist at the University of Melbourne.
Enhancers serve as landing pads for proteins that turn genes on. Only specific proteins are granted landing privileges and only at prescribed times of development in particular types of cells. The Col2a1 enhancer turns the gene on only in chondrocytes — cartilage-producing cells— in mouse embryos. The enhancer works similarly in birds and mammals, so the researchers hoped that the thylacine DNA would also produce a familiar pattern of gene activity.
That hope was fulfilled. Mouse embryos engineered with the thylacine enhancer turned on production of a marker that the researchers use to track gene activity. The enhancer worked only in chondrocytes.
The new study is the first using extinct DNA that does not encode a protein but controls how genes are turned on and off. In previous studies, mammoth and Neandertal genes were used to produce proteins in cell culture, not in living animals.
“This is the next logical step to try to bring ancient DNA into an animal or biological system,” says Stephen Schuster, a genomicist at Pennsylvania State University in University Park. Researchers might use the technique to find enhancers and other regulatory elements that could make a chicken look like a dinosaur or an elephant look like a mammoth, he said. But such methods, even if they could achieve such dramatic results, would not bring back dodos, dinosaurs and mammoths.
“If you had a very hairy African elephant, that would be a first step to looking like a mammoth, but of course it wouldn’t be a mammoth. It would just be a weird-looking elephant,” Schuster says.
Even though the thylacine enhancer seems to work the same way as the mouse enhancer does, that’s no guarantee that the researchers have the correct answer to how thylacine DNA functions. Mice and marsupials are so different that sometimes enhancers might misbehave when placed in a mouse, giving researchers the wrong impression about how such bits of DNA worked in extinct animals, says Lalueza-Fox.
“To use an animal model is always difficult, but to use an eutherian [placental] animal model for a marsupial is really quite risky,” he says.
Other researchers concede that genetically engineered mice might sometimes yield misleading data, but see no alternative way to study gene function from extinct species.
“The problem with extinct animals is that they’re extinct,” says Michael Hofreiter, an evolutionary biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “Cell cultures or the mouse models are the only possibility we have of learning how non-coding DNA worked in extinct animals. The question is not whether this is the best way forward — it’s the only way forward.”
These kinds of studies are necessary to understand where and when genes are turned on and off in the bodies of extinct animals. That information may be encoded in the DNA of the animals, but predicting how variations between two species changes gene function is not well understood. Such studies could show how the thylacine got its stripes or what made mammoths so woolly.
Even armed with information about how thylacine genes worked, the technology used in the study is unlikely to bring back the Tasmanian tiger, Hofreiter says. In order to re-create the thylacine from a mouse using this technique, researchers would have to replace the mouse genome bit by bit, using about 10 million short pieces of DNA. That would take years and be would be extremely costly, not to mention that at some point, a chimeric animal (part-mouse, part-thylacine) would be unlikely to survive, he says.
Schuster favors a bigger, bolder approach to re-creating extinct animals, one that admittedly is still science fiction. He would stitch together entire chromosomes from an extinct animal and replace a host animal’s chromosomes with the synthetic creations. In that way, an elephant’s genetic material might be replaced with mammoth DNA, essentially reincarnating the Ice Age icon.
Scientists are only just beginning to learn how to create whole chromosomes.
“With DNA we’re very good at reading information, but we’re not good at writing. It’s like we’ve got a computer, but we don’t have a printer,” Schuster says.
Thylacines have no living counterpart. Their closest living relatives are Tasmanian devils, but no one has ever genetically engineered a Tasmanian devil, making it an unlikely host should the technology to clone extinct animals become available.
Re-creating extinct organisms captures the imagination, Schuster says, but it is far easier and less expensive to protect the endangered animals still living on Earth.
Monday, May 12, 2008
Human ageing gene found in flies
WASHINGTON: Researchers from University of Oxford and The Open University have found a gene in fruit flies that would give a fast and effective way to investigate important aspects of human ageing. Dr Lynne Cox and Dr Robert Saunders have discovered the human aging gene in fruit flies, which means the flies, could now be used as a model to study the effects ageing has on DNA. "We study a premature human ageing disease called Werner syndrome to help us understand normal ageing. The key to this disease is that changes in a single gene (called WRN) mean that patients age very quickly," said Dr Cox from the University of Oxford. "Scientists have made great progress in working out what this gene does in the test tube, but until now we haven't been able to investigate the gene to look at its effect on development and the whole body. By working on this gene in fruit flies, we can model human ageing in a powerful experimental system," Cox added. The fruit flies would help the researchers in understanding the ageing process along with critical aspects at cellular, genetic and biochemical levels. "This work shows for the first time that we can use the short-lived fruit fly to investigate the function of an important human ageing gene," said Dr Robert Saunders from The Open University, "We have opened up the exciting possibility of using this model system to analyse the way that such genes work in a whole organism, not just in single cells, he added. The researchers have identified the fruit fly equivalent of the key human ageing gene known as WRN. They find that flies with damage to this gene share important features with people suffering from the rapid ageing condition Werner syndrome, who also have damage to the WRN gene. In particular, the DNA, or genetic blueprint, is unstable in the flies that have the damaged version of the gene and the chromosomes are often altered. The researchers show that the fly's DNA becomes rearranged, with genes being swapped between chromosomes. In patients with Werner syndrome, this genome instability leads to cancer. Cells derived from Werner syndrome patients are extremely sensitive to a drug often used to treat cancers: the researchers show that the flies that have the damaged gene are killed by even very low doses of the drug. "Fruit flies are already used as a model for the genetics behind mechanisms that underlie normal functioning of the human body and it is great news that this powerful research tool can be applied to such an important area of study into human health," said Professor Nigel Brown, Director of Science and Technology, Biotechnology and Biological Sciences Research Council. The study appears in the journal Aging Cell .
DNA test to take less than 45 mins?
WASHINGTON: A University of Virginia forensic chemist has developed a method for handling rape evidence that reduces part of the DNA analysis time from 24 hours to as little as 30 to 45 minutes. The method also improves the sperm cell recovery rate by 100 percent. If adopted by forensic labs and accepted by courts the time-efficient method, developed by Jessica Voorhees Norris, a PhD candidate in forensic chemistry at UVA, could potentially reduce the backlog of evidence asking for analysis, just within a few months. "There is an overwhelming demand for DNA analysis of sexual assault evidence, but laboratories have neither the funding nor the manpower to handle the caseload in a timely manner. Juries have come to expect DNA evidence in sexual assault cases, but forensic labs are not able to perform in a timely and efficient manner due to limitations in the currently used technologies," said Norris. In case a woman reports being sexually assaulted, a sample is taken from the vagina with a cotton swab for sending to the forensic lab. The DNA analysis in high-profile cases is done immediately, which also involves overnight incubation. On the other hand, in routine cases the sample is put into storage for as long as a year and is not analysed till the case approaches a court date, often causing the sample to degrade. Getting the results in lab involves a number of steps wherein first the female and male cells are separated. This requires an overnight incubation period. Once the DNA is extracted, profiles, in effect, are generated for both the victim and the attacker. This two decades old practice is quite time-consuming. And later, the DNA sample is matched with the perpetrator's DNA taken from his saliva. However, Norris' method simplifies the method for separating the male and female DNA fractions, eliminating the need for the overnight incubation while doubling the recovery of sperm cells. "This new process works extraordinarily well and could be implemented in forensic labs today," said Norris. Norris presented her findings at a recent meeting of the American Academy of Forensic Scienc e.
Scientists to collect DNA of all trees
NEW YORK: The New York Botanical Garden may be best known for its orchid shows and colourful blossoms, but its researchers are about to lead a global effort to capture DNA from thousands of tree species from around the world. The Bronx garden is hosting a meeting this week where participants from various countries will lay the groundwork for how the two-year undertaking to catalogue some of the Earth's vast biodiversity will proceed. The project is known as TreeBOL, or tree barcode of life. A section of the DNA would be used as a barcode. The resulting database will help identify many of the world's existing plant species, where they are located and whether they are endangered.
Cutting hunger by blocking an enzyme
CHICAGO: Blocking a single brain enzyme helped short-circuit a key hunger signal in mice and made them eat less, lose weight and have better blood sugar control, US researchers said on Tuesday. While much more research lies ahead, they said the finding may lead to new treatments for obesity and diabetes in humans. "We believe we have identified an important drug development target that could potentially turn into a metabolic triple play: appetite control, weight loss and blood sugar management," said Tony Means of Duke University Medical Center in Durham, North Carolina, whose study appears in the journal Cell Metabolism. Means's team focused on the enzyme CaMKK2, which plays a role in appetite stimulation in mice and in humans. Found in a region of the brain known as the hypothalamus, it takes its orders from a hormone released in the gut known as ghrelin, which is released when the stomach is empty. In a separate brain imaging study in the same journal, researchers at the Neurological Institute at McGill University in Montreal showed that ghrelin not only makes people feel hungry, but it makes food look more appealing by activating pleasure signals in the brain. Means's idea is to find a way to interrupt ghrelin's activity by toning down the CaMKK2 enzyme's response to the hunger signal. His team found that mice genetically engineered to lack the enzyme CaMKK2 stayed slim regardless of whether they were on a low-fat or high-fat diet. "They don't gain as much weight as wild type mice," Means said in an interview
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