24 August 2012 by Michael Marshall
THE latest twist in the origin-of-life tale is double helical. Chemists are close to demonstrating that the building blocks of DNA can form spontaneously from chemicals thought to be present on the primordial Earth. If they succeed, their work would suggest that DNA could have predated the birth of life.
Lurking at the dawn of time (Image: Snorri Gunnarsson/Flickr/Getty)
DNA is essential to almost all life on Earth, yet most biologists think that life began with RNA. Just like DNA, it stores genetic information. What’s more, RNA can fold into complex shapes that can clamp onto other molecules and speed up chemical reactions, just like a protein, and it is structurally simpler than DNA, so might be easier to make.
After decades of trying, in 2009 researchers finally managed to generate RNA using chemicals that probably existed on the early Earth. Matthew Powner, now at University College London, and his colleagues synthesised two of the four nucleotides that make up RNA. Their achievement suggested that RNA may have formed spontaneously - powerful support for the idea that life began in an “RNA world”.
Read more …
Filed under science biology DNA life RNA neuroscience DNA nucleotides biochemistry
Better diagnosis and treatment of a crippling inherited nerve disorder may be just around the corner thanks to an international team that spanned Asia, Europe and the United States. The team had been hunting DNA strands for the cause of the inherited nerve disorder known as spinocerebellar ataxia, or SCA. The disease causes progressive loss of balance, muscle control and ability to walk. Thanks to their diligence and detective work they have discovered the disease gene in a region of chromosome 1 where another group from the Netherlands had previously shown linkage with a form of SCA called SCA19, and the Taiwanese group on the new paper had shown similar linkage in a family for a form of the disease that was then called SCA22. The international team, from France, Japan, Taiwan and the USA have published their discovery in the Annals of Neurology. The Dutch group has also published results in the same issue of the journal.
Their paper reveals that mutations in the gene KCND3 were found in six families in Asia, Europe and the United States that have been haunted by SCA. Their results will allow for a better understanding of why nerves in the brain’s movement-controlling centre die, and how new DNA mapping techniques can find the causes of other diseases that run in families.
Margit Burmeister, Ph.D., a geneticist at University of Michigan Health System (U-M), helped lead the work and stressed that the gene could not have been found without a great deal of DNA detective work and the cooperation of the families who volunteered to let researchers map all the DNA of multiple members of their family tree. ‘We combined traditional genetic linkage analysis in families with inherited diseases with whole exome sequencing of an individual’s DNA, allowing us to narrow down and ultimately identify the mutation,’ she says. ‘This new type of approach has already resulted in many new gene identifications, and will bring in many more.’
The gene is very important as it manages the production of a protein that allows nerve cells to ‘talk’ to one another through the flow of potassium. Pinpointing its role as a cause of ataxia will now allow more people with ataxia to learn the exact cause of their disease, give a very specific target for new treatments, and perhaps allow the families to stop the disease from affecting future generations.
U-M neurologist Vikram Shakkottai, M.D., Ph.D., an ataxia specialist and co-author on the paper, also notes that the new genetic information will help patients find out the specific cause of their disease. He and his colleagues are already working to find drugs that might alter potassium flow, and provide a treatment for a group of diseases that currently are only treated with supportive care such as physical activity and balance training as patients deteriorate. ‘Many of the families who come to our clinic for treatment don’t have a recognised genetic mutation, so it’s important to find new genetic mutations to explain their symptoms,’ says Shakkottai. ‘But at the same time, this research is helping us understand a common mechanism of nerve cell dysfunction in progressive and non-progressive disease.’
Their findings however are not restricted to just ataxia. The researchers were also able to show that when KCND3 is mutated, it causes poor communication between nerve cells in the cerebellum as well as the death of those cells. This discovery could aid research on other neurological disorders involving balance and movement.
The Dutch team, that also published its findings about KCND3 at the same time, studied families in the Netherlands and found that mutations on the gene are responsible for SCA19, the cause of which had up until now been a mystery. ‘In other words, mutations in this gene are not uncommon and present all over the world,’ says Burmeister. ‘This means that in the future, this gene should be tested for mutations as part of a clinical genetic test panel for patients with ataxia symptoms. Because a generation can be skipped, it may even be relevant in some sporadic cases - those where the patient isn’t aware of any other family members with a similar disease.’
Source: Cordis News
Filed under DNA mutations genetics neuroscience science KCND3 SCA ataxia
Differentiating neuronal cells (actin, microtubules and DNA)
Image by Dr. Torsten Wittmann (The Scripps Research Institute in La Jolla, California)
Filed under biology cellular differentiation neuron neuroscience science DNA
TAU research says genetics can reveal your geographic ancestral origin
While your DNA is unique, it also tells the tale of your family line. It carries the genetic history of your ancestors down through the generations. Now, says a Tel Aviv University researcher, it’s also possible to use it as a map to your family’s past.
Prof. Eran Halperin of TAU’s Blavatnik School of Computer Science and Department of Molecular Microbiology and Biotechnology, along with a group of researchers from University of California, Los Angeles, are giving new meaning to the term “genetic mapping.” Using a probabilistic model of genetic traits for every coordinate on the globe, the researchers have developed a method for determining more precisely the geographical location of a person’s ancestral origins.
The new method is able to pinpoint more specific locations for an individual’s ancestors, for example placing an individual’s father in Paris and mother in Barcelona. Previous methods would “split the difference” and place this origin inaccurately at a site between those two cities, such as Lyon.
Published in the journal Nature Genetics, this method has the potential to reveal the ancestry, origins, and migration patterns of many different human and animal populations. It could also be a new model for learning about the genome.
Points of origin
There are points in the human genome called SNPs that are manifested differently in each individual, explains Prof. Halperin. These points mutated sometime in the past and the mutation was then passed to a large part of the population in a particular geographic region. The probability of a person possessing these mutations today varies depending on the geographical location of those early ancestors.
"We wanted to ask, for example, about the probability of having the genetic mutation ‘A’ in a particular position on the genome based on geographical coordinates," he says. When you look at many of these positions together in a bigger picture, it’s possible to group populations with the same mutation by point of origin.
To test their method, Prof. Halperin and his fellow researchers studied DNA samples from 1,157 people from across Europe. Using a probabilistic mathematical algorithm based on mutations in the genome, they were able to accurately determine their ancestral point or points of origin using only DNA data and the new mathematical model, unravelling genetic information to ascertain two separate points on the map for the mother and father. The researchers hope to extend this model to identify the origins of grandparents, great-grandparents, and so on.
The new method could provide information that has applications in population genetic studies — to study a disease that impacts a particular group, for example. Researchers can track changes in different genomic traits across a map, such as the tendency for southern Europeans to have a mutation in a gene that causes lactose intolerance, a mutation missing from that gene in northern Europeans.
A closer look at migration
The researchers believe that their model could have also relevance for the animal kingdom, tracking the movement of animal populations. “In principle, you could figure out where the animals have migrated from, and as a result learn about habitat changes due to historical climate change or other factors,” says Prof. Halperin.
Source: Tel Aviv University
Filed under science neuroscience genetics DNA genetic mapping
DNA: The Ultimate Hard Drive
When it comes to storing information, hard drives don’t hold a candle to DNA. Our genetic code packs billions of gigabytes into a single gram. A mere milligram of the molecule could encode the complete text of every book in the Library of Congress and have plenty of room to spare. All of this has been mostly theoretical—until now. In a new study, researchers stored an entire genetics textbook in less than a picogram of DNA—one trillionth of a gram—an advance that could revolutionize our ability to save data.
A few teams have tried to write data into the genomes of living cells. But the approach has a couple of disadvantages. First, cells die—not a good way to lose your term paper. They also replicate, introducing new mutations over time that can change the data.
To get around these problems, a team led by George Church, a synthetic biologist at Harvard Medical School in Boston, created a DNA information-archiving system that uses no cells at all. Instead, an inkjet printer embeds short fragments of chemically synthesized DNA onto the surface of a tiny glass chip. To encode a digital file, researchers divide it into tiny blocks of data and convert these data not into the 1s and 0s of typical digital storage media, but rather into DNA’s four-letter alphabet of As, Cs, Gs, and Ts. Each DNA fragment also contains a digital “barcode” that records its location in the original file. Reading the data requires a DNA sequencer and a computer to reassemble all of the fragments in order and convert them back into digital format. The computer also corrects for errors; each block of data is replicated thousands of times so that any chance glitch can be identified and fixed by comparing it to the other copies.
To demonstrate its system in action, the team used the DNA chips to encode a genetics book co-authored by Church. It worked. After converting the book into DNA and translating it back into digital form, the team’s system had a raw error rate of only two errors per million bits, amounting to a few single-letter typos. That is on par with DVDs and far better than magnetic hard drives. And because of their tiny size, DNA chips are now the storage medium with the highest known information density, the researchers report online today in Science.
Don’t replace your flash drive with genetic material just yet, however. The cost of the DNA sequencer and other instruments “currently makes this impractical for general use,” says Daniel Gibson, a synthetic biologist at the J. Craig Venter Institute in Rockville, Maryland, “but the field is moving fast and the technology will soon be cheaper, faster, and smaller.” Gibson led the team that created the first completely synthetic genome, which included a “watermark” of extra data encoded into the DNA. The researchers used a three-letter coding system that is less efficient than the Church team’s but has built-in safeguards to prevent living cells from translating the DNA into proteins. “If DNA is going to be used for this purpose, and outside a laboratory setting, then you would want to use DNA sequence that is least likely to be expressed in the environment,” he says. Church disagrees. Unless someone deliberately “subverts” his DNA data-archiving system, he sees little danger.
Filed under science biology genetics DNA neuroscience genomics
ScienceDaily (Aug. 15, 2012) — Acute stress alters the methylation of the DNA and thus the activity of certain genes. This is reported by researchers at the Ruhr-Universität Bochum together with colleagues from Basel, Trier and London for the first time in the journal Translational Psychiatry. “The results provide evidence how stress could be related to a higher risk of mental or physical illness,” says Prof. Dr. Gunther Meinlschmidt from the Clinic of Psychosomatic Medicine and Psychotherapy at the LWL University Hospital of the RUB. The team looked at gene segments which are relevant to biological stress regulation.
In stressful social situations, the methylation patterns (bright spheres) of the DNA change. (Credit: Illustration: Christoph Unternährer and Christian Horisberger)
Epigenetics — the “second code” — regulates gene activity
Our genetic material, the DNA, provides the construction manual for the proteins that our bodies need. Which proteins a cell produces depends on the cell type and the environment. So-termed epigenetic information determines which genes are read, acting quasi as a biological switch. An example of such a switch is provided by methyl (CH3) groups that attach to specific sections of the DNA and can remain there for a long time — even when the cell divides. Previous studies have shown that stressful experiences and psychological trauma in early life are associated with long-term altered DNA methylation. Whether the DNA methylation also changes after acute psychosocial stress, was, however, previously unknown.
Two genes tested
To clarify this issue, the research group examined two genes in particular: the gene for the oxytocin receptor, i.e. the docking site for the neurotransmitter oxytocin, which has become known as the “trust hormone” or “anti-stress hormone”; and the gene for the nerve growth factor Brain-Derived Neurotrophic Factor (BDNF), which is mainly responsible for the development and cross-linking of brain cells. The researchers tested 76 people who had to participate in a fictitious job interview and solve arithmetic problems under observation — a proven means for inducing acute stress in an experiment. For the analysis of the DNA methylation, they took blood samples from the subjects before the test as well as ten and ninety minutes afterwards.
DNA methylation changes under acute psychosocial stress
Stress had no effect on the methylation of the BDNF gene. In a section of the oxytocin receptor gene, however, methylation already increased within the first ten minutes of the stressful situation. This suggests that the cells formed less oxytocin receptors. Ninety minutes after the stress test, the methylation dropped below the original level before the test. This suggests that the receptor production was excessively stimulated.
Possible link between stress and disease
Stress increases the risk of physical or mental illness. The stress-related costs in Germany alone amount to many billions of Euros every year. In recent years, there have been indications that epigenetic processes are involved in the development of various chronic diseases such as cancer or depression. “Epigenetic changes may well be an important link between stress and chronic diseases” says Prof. Meinlschmidt, Head of the Research Department of Psychobiology, Psychosomatics and Psychotherapy at the LWL University Hospital. “We hope to identify more complex epigenetic stress patterns in future and thus to be able to determine the associated risk of disease. This could provide information on new approaches to treatment and prevention.” The work originated within the framework of an interdisciplinary research consortium with the University of Trier, the University of Basel and King’s College London. The German Research Foundation and the Swiss National Science Foundation supported the study.
Source: Science Daily
Filed under brain neuroscience psychology science stress disease DNA methylation DNA
The UT Dallas “tag and track” method not only sheds light on how DNA loops form, but also might be adapted to screen drugs for effectiveness against certain viruses that shuffle genetic material, such as HIV.
Until now, scientists primarily had “snapshots” of the initial and final stages of DNA loop formation, with only limited information about what happens during the intermediate steps.
"Scientists have known for more than 30 years that DNA looping is an important part of molecular biology and gene regulation, but until our work, there have been few serious attempts to understand the basic biophysics of the process, … We estimate that using fluorescence-based methods such as this for drug screening could be as much as 10,000 times more efficient than methods that are currently used," -Dr. Stephen Levene, professor of bioengineering, molecular and cell biology, and phyiscs at UT Dallas.
Filed under DNA biology genetics neuroscience science virus DNA looping
These days, 3D printing is being used to mock up far more complex systems, says Arthur Olson, who founded the molecular graphics lab at the Scripps Research Institute in La Jolla, California, 30 years ago. These include molecular environments made up of thousands of interacting proteins, which would be onerous-to-impossible to make any other way. With 3D printers, Olson says, “anybody can make a custom model”. But not everybody does: many researchers lack easy access to a printer, aren’t aware of the option or can’t afford the printouts (which can cost $100 or more).
Read more
Filed under 3D printing biology neuroscience research science molecules DNA
'Selfish' DNA in animal mitochondria offers possible tool to study aging
Researchers at Oregon State University have discovered, for the first time in any animal species, a type of “selfish” mitochondrial DNA that is actually hurting the organism and lessening its chance to survive – and bears a strong similarity to some damage done to human cells as they age.
Such selfish mitochondrial DNA has been found before in plants, but not animals. In this case, the discovery was made almost by accident during some genetic research being done on a nematode, Caenorhabditis briggsae – a type of small roundworm.
“We weren’t even looking for this when we found it, at first we thought it must be a laboratory error,” said Dee Denver, an OSU associate professor of zoology. “Selfish DNA is not supposed to be found in animals. But it could turn out to be fairly important as a new genetic model to study the type of mitochondrial decay that is associated with human aging.”
Filed under DNA animals roundworm biology science neuroscience mitochondria ageing
Boosting Antipsychotic Drugs
While antipsychotic drugs alleviate the symptoms of many people with schizophrenia, around a third of patients resist such treatments. A new study, led by Javier Gonzalez-Maeso of the Mount Sinai School of Medicine, suggests that this frustrating intractability depends on how DNA is packaged.
Gonzalez-Maeso and his colleagues found that antipsychotic drugs can suppress the expression of glutamate receptors in the brain, stunting their effectiveness as treatments for schizophrenia. But the researchers also found a way of boosting the effects of antipsychotics—by pairing them with drugs that block the gene suppression pathway.
Filed under DNA antipsychotic drugs brain genomics neuroscience receptors schizophrenia science treatment
