Paddlefish’s doubled genome may question theories on limb evolution
The American paddlefish — known for its bizarre, protruding snout and eggs harvested for caviar — duplicated its entire genome about 42 million years ago, according to a new study published in the journal Genome Biology and Evolution. This finding may add a new twist to the way scientists study how fins evolved into limbs since the paddlefish is often used as a proxy for a more representative ancestor shared by humans and fishes.
“We found that paddlefish have had their own genome duplication,” said Karen Crow, assistant professor of biology at San Francisco State University. “This creates extra genetic material that adds complexity to comparative studies. It may change the way we interpret studies on limb development.”
In order to study how human limbs develop, scientists compare the limb-building genes found in mice with fin-building genes found in fishes. Previous research on paddlefish has suggested that fishes possessed the genetic toolkit required to grow limbs long before the evolution of the four-limbed creatures (tetrapods) that developed into reptiles, birds, amphibians and mammals.
In the last decade, paddlefish have become a useful benchmark in evolutionary studies because their position on the evolutionary tree makes them a reasonably good proxy for the ancestor of the bony fishes that evolved into tetrapods such as humans. However, the fact that paddlefish underwent a genome duplication could complicate what its genes tell us about the fin-to-limb transition, says Crow.
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ScienceDaily (Aug. 16, 2012) — Researchers have found what they believe is the key to understanding why the human brain is larger and more complex than that of other animals.
The human brain, with its unequaled cognitive capacity, evolved rapidly and dramatically.
"We wanted to know why," says James Sikela, PhD, who headed the international research team that included researchers from the University of Colorado School of Medicine, Baylor College of Medicine and the National Institutes of Mental Health. "The size and cognitive capacity of the human brain sets us apart. But how did that happen?"
"This research indicates that what drove the evolutionary expansion of the human brain may well be a specific unit within a protein — called a protein domain — that is far more numerous in humans than other species."
The protein domain at issue is DUF1220. Humans have more than 270 copies of DUF1220 encoded in the genome, far more than other species. The closer a species is to humans, the more copies of DUF1220 show up. Chimpanzees have the next highest number, 125. Gorillas have 99, marmosets 30 and mice just one. “The one over-riding theme that we saw repeatedly was that the more copies of DUF1220 in the genome, the bigger the brain. And this held true whether we looked at different species or within the human population.”
Sikela, a professor at the CU medical school, and his team also linked DUF1220 to brain disorders. They associated lower numbers of DUF1220 with microcephaly, when the brain is too small; larger numbers of the protein domain were associated with macrocephaly, when the brain is too large.
The findings were reported today in the online edition of The American Journal of Human Genetics. The researchers drew their conclusions by comparing genome sequences from humans and other animals as well as by looking at the DNA of individuals with microcephaly and macrocephaly and of people from a non-disease population.
"The take home message was that brain size may be to a large degree a matter of protein domain dosage," Sikela says. "This discovery opens many new doors. It provides new tools to diagnose diseases related to brain size. And more broadly, it points to a new way to study the human brain and its dramatic increase in size and ability over what, in evolutionary terms, is a short amount of time."
Source: Science Daily
Filed under DUF1220 brain evolution genetics genomics neuroscience psychology science protein
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
The first genome-wide searches for the genes responsible for Tourette syndrome and obsessive-compulsive disorder have uncovered a few clues to the underpinnings of both disorders.
Tourette syndrome is a neurological disorder characterized by muscle and vocal tics such as eye blinking, throat clearing and uttering taboo words or phrases. Tourette’s often co-occurs with obsessive-compulsive disorder (OCD), a mental illness marked by repetitive behaviors and anxiety-producing intrusive thoughts.
Neither Tourette syndrome nor OCD are simple enough to be traced to a single gene, but two new studies detailed today (Aug. 14) in the journal Molecular Psychiatry find several locations on the human chromosome that may contribute to the conditions.
A DNA molecule.
CREDIT: Giovanni Cancemi | Shutterstock
"Both disorders clearly have a complex underlying genetic architecture, and these two studies lay the foundation for understanding the underlying genetic etiology of Tourette syndrome and OCD," said Jeremiah Scharf, a neurologist at Massachusetts General Hospital in Boston, who worked on both projects.
Genetics of Tourette Syndrome
In the Tourette syndrome study, Scharf and his colleagues compared the genomes of more than 1,200 people with the disorder with the genomes of nearly 5,000 healthy individuals. They conducted what’s called a genome-wide association study, scanning hundreds of thousands of genetic variants from across the genomes to see if any were more common in the people with the disorder.
They found that no single genetic signal was significantly different between the two genomes, meaning that the researchers could not rule out random chance as the reason for any given difference. But among the top genetic variations, the researchers found an unusually high number that influence levels of gene expression in the frontal lobe of the brain — a region important in both Tourette syndrome and OCD, Scharf said.
One intriguing gene that varied the most between Tourette- and non-Tourette genomes was called COL27A1, a gene that encodes a collagen protein found in cartilage. The same gene is also active in the cerebellum, a brain region important for motor control during development. More research will be necessary to find what link, if any, COL27A1 has to Tourette syndrome, Scharf said.
The architecture of OCD
In a separate study, the scientists carried out the same analysis on healthy genomes as well as about 1,500 people with obsessive-compulsive disorder. Again, no one gene rose to the top as a definitive OCD gene, but the results revealed a good candidate near a gene called BTBD3, which is involved in multiple cellular functions. BTBD3 is very active in the brain during childhood and adolescent development, when OCD often first appears. It’s also related to a gene called BTBD9, which has been linked to Tourette syndrome in the past.
This first genome-wide pass is bound to turn up some false positives, Scharf said, so researchers will now need to home in on the intriguing genes in larger samples of people. They are also merging the two studies to look for genetic linkages that might explain why Tourette syndrome and OCD so frequently co-occur.
"The important thing this study does is that it really brings Tourette syndrome and OCD into the company of a number of other psychiatric diseases, which people have studied using genome-wide association," Scharf said, citing autism, schizophrenia and bipolar disorder as examples. “Now that we have these data for Tourette syndrome and OCD, we can work with investigators who are studying those other diseases to try to see what we can learn about what variants are shared between different neurodevelopment disorders.”
Source: Live Science
Filed under OCD brain neuroscience psychology science tourette syndrome genomics
August 7, 2012
Investigators at Boston University School of Medicine (BUSM) and Veterans Affairs (VA) Boston Healthcare System have identified a new gene linked to post-traumatic stress disorder (PTSD). The findings, published online in Molecular Psychiatry, indicate that a gene known to play a role in protecting brain cells from the damaging effects of stress may also be involved in the development of PTSD.
The article reports the first positive results of a genome-wide association study (GWAS) of PTSD and suggests that variations in the retinoid-related orphan receptor alpha (RORA) gene are linked to the development of PTSD.
Mark W. Miller, PhD, associate professor at BUSM and a clinical research psychologist in the National Center for PTSD at VA Boston Healthcare System was the study’s principal investigator. Mark Logue, PhD, research assistant professor at BUSM and Boston University School of Public Health and Clinton Baldwin, PhD, professor at BUSM, were co-first authors of the paper.
PTSD is a psychiatric disorder defined by serious changes in cognitive, emotional, behavioral and psychological functioning that can occur in response to a psychologically traumatic event. Previous studies have estimated that approximately eight percent of the U.S. population will develop PTSD in their lifetime. That number is significantly greater among combat veterans where as many as one out of five suffer symptoms of the disorder.
Previous GWAS studies have linked the RORA gene to other psychiatric conditions, including attention-deficit hyperactivity disorder, bipolar disorder, autism and depression.
"Like PTSD, all of these conditions have been linked to alterations in brain functioning, so it is particularly interesting that one of the primary functions of RORA is to protect brain cells from the damaging effects of oxidative stress, hypoxia and inflammation," said Miller.
Participants in the study were approximately 500 male and female veterans and their intimate partners, all of whom had experienced trauma and approximately half of whom had PTSD. The majority of the veterans had been exposed to trauma related to their military experience whereas their intimate partners had experienced trauma related to other experiences, such as sexual or physical assault, serious accidents, or the sudden death of a loved one. Each participant was interviewed by a trained clinician, and DNA was extracted from samples of their blood.
The DNA analysis examined approximately 1.5 million genetic markers for signs of association with PTSD and revealed a highly significant association with a variant (rs8042149) in the RORA gene. The researchers then looked for evidence of replication using data from the Detroit Neighborhood Health Study where they also found a significant, though weaker, association between RORA and PTSD.
"These results suggest that individuals with the RORA risk variant are more likely to develop PTSD following trauma exposure and point to a new avenue for research on how the brain responds to trauma," said Miller.
Provided by Boston University Medical Center
Source: medicalxpress.com
Filed under science neuroscience brain psychology PTSD stress genomics
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
Cancer May Result From Wrong Number of Genes
When a young person develops cancer, doctors most often assume that genetics are the reason, because the patient hasn’t lived long enough to accumulate environmental damage. But it’s been hard to find the faulty DNA behind many tumors. Now, using new genomic technology, scientists have discovered a novel explanation for some testicular cancers, the most common cause of cancer in men under 35. Rather than being triggered by a single gene mutation, the tumors are caused by too many or too few copies of a gene in a person’s cells. These “copy number variations” have been linked to other conditions such as autism, but never before to cancer.
Filed under brain cancer genes genomics neuroscience psychology science testicular cancer genetics
Brain Expression
Researchers map the expression patterns of 1,000 genes in the human brain.
The paper
H. Zeng et al., “Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures,” Cell, 149:48-96, 2012.
The finding
Whole-genome sequencing has given researchers a good sense of which genes are shared between, for example, humans and mice. But little is known about how the expression patterns of these genes differ. Hongkui Zeng of the Allen Institute for Brain Science in Seattle, Washington, and colleagues took slices of human brains collected from postmortem biopsies and tested the expression of 1,000 key neuronal genes. They found that about 21 percent of the gene-expression profiles differed between the two species.
The sliver
Researchers took thin slices from regions of the brain involved in processing visual and sensory information and scanned them for the in situ expression of 1,000 genes that act as markers of cell type or are involved in disease, evolution, or cortical function. They compared gene expression of three areas of the cortex across 46 donors with corresponding mouse-brain slices, which had been analyzed previously at the Allen Institute.
The difference
The differences between humans and mice “often manifested in a cell type-specific way,” said Zeng, or involved in between-cell communications. “The disease genes are all very well conserved,” which bodes well for researchers using mice as models of disease, she says.
The impact
“The mouse model is used extensively in neuroscience research, and it’s assumed to be a surrogate for the human,” says Daniel Geschwind, a neurogeneticist at the University of California, Los Angeles. Knowing the specific differences “gives you a sense that many things are conserved, but also provides some guidance as to the ones that aren’t.”
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Artificial Beginnings: Understanding the Origin of Life by Recreating It
The Origin of Life on Earth was certainly, in retrospect, and from the human vantage point, the most fateful event in the history of the Universe. On a young, tepid Earth chemistry sprung into biology and set course on a four billion year journey that would eventually lead to us. However, all traces of the first, primitive organisms have vanished. They were outcompeted and devoured by their evolutionary descendents, leaving nothing to form fossils. Though we will never be able to set eyes on the first Earthlings, the first pioneers, we can understand what they must have been like through more subtle, indirect approaches. Comparative biochemistry across the whole of life takes us back quite a ways, though not to the first cells. The most recent common ancestor shared by all living organisms—bacteria, plants, animals, fungi, archaea, and unicellular eukaryotes like amoebae—was born long after the first cell ceased to exist. The only way we can truly understand what life must have been like in its earliest days is to create it ourselves.
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Californian biotech firm Life Technologies is the first team to register for the $10 million (£6.4m) Archon Genomics X Prize, which will be a race to sequence the genomes of 100 centenarians.
The prize was first announced in 2006, and is a joint effort between the X Prize Foundation and geneticist J Craig Venter. It’s supposed to stimulate the development of less expensive sequencing technologies, and establish a clinical standard for DNA research.
Interested parties have until May 2013 to register. Late that year, in September, each team will have 30 days to sequence the genomes of 100 people, at a cost of $1,000 (£643) or less.
The DNA has been donated by 100 100 year old people from all over the world, to make the competition “scientifically valuable and more meaningful to the general public”. That way, the prize can double up as medical research into the science of healthy aging and longevity.
Life Technologies’ secret weapon is the Ion Proton Sequencer, which it describes as a “semiconductor device that enables chemical signals to be directly translated into digital information for the first time” — a bit like the CMOS imager in an iPhone, which turns photons into electrons.
"It would have cost $100 million and taken 33 years to meet this challenge when the competition was announced in 2006," said Jonathan Rothberg, CEO and founder of Life Technology’s Ion Torrent brand. "The Ion Proton sequencer is designed to sequence a human genome for $1,000 in just a few hours."
Source: Wired
Filed under Archon Genomics X prize DNA biology genetics genomics ion proton sequencer medicine neuroscience psychology research science technology X prize foundation ageing
