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Genomically encoded analog memory with precise in vivo DNA writing using living bacteria populations

Genomically encoded analog memory with precise in vivo DNA writing using living bacteria populations | Amazing Science | Scoop.it

MIT engineers have transformed the genome of the bacterium E. coli into a long-term storage device for memory. They envision that this stable, erasable, and easy-to-retrieve memory will be well suited for applications such as sensors for environmental and medical monitoring.“You can store very long-term information,” says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering. “You could imagine having this system in a bacterium that lives in your gut, or environmental bacteria. You could put this out for days or months, and then come back later and see what happened at a quantitative level.


”The new strategy, described in the Nov. 13, 2014 issue of the journal Science ("Genomically encoded analog memory with precise in vivo DNA writing in living cell populations"), overcomes several limitations of existing methods for storing memory in bacterial genomes, says Lu, the paper’s senior author. Those methods require a large number of genetic regulatory elements, limiting the amount of information that can be stored.The earlier efforts are also limited to digital memory, meaning that they can record only all-or-nothing memories, such as whether a particular event occurred. Lu and graduate student Fahim Farzadfard, the paper’s lead author, set out to create a system for storing analog memory, which can reveal how much exposure there was, or how long it lasted. To achieve that, they designed a “genomic tape recorder” that lets researchers write new information into any bacterial DNA sequence.


The researchers showed that SCRIBE enables the recording of arbitrary transcriptional inputs into DNA storage registers in living cells by translating regulatory signals into ssDNAs. In E. coli, they expressed ssDNAs from engineered retrons that use a reverse transcriptase protein to produce hybrid RNA-ssDNA molecules. These intracellularly expressed ssDNAs are targeted into specific genomic loci where they are recombined and converted into permanent memory. The team could show that genomically stored information can be readily reprogrammed by changing the ssDNA template and controlled via both chemical and light inputs. This demonstrates that genomically encoded memory can be read with a variety of techniques, including reporter genes, functional assays, and high-throughput DNA sequencing.


SCRIBE enables the recording of analog information such as the magnitude and time span of exposure to an input. This convenient feature is facilitated by the intermediate recombination rate of our current system (~10–4 recombination events per generation), which we validated via a mathematical model and computer simulations. For example, the scientists stored the overall exposure time to chemical inducers in the DNA memory of bacterial populations for 12 days (~120 generations), independently of the induction pattern. The frequency of mutants in these populations was linearly related to the total exposure time. Furthermore, they were able to demonstrate that SCRIBE-induced mutations can be written and erased and can be used to record multiple inputs across the distributed genomic DNA of bacterial populations.

Finally, they could show that SCRIBE memory can be decomposed into independent “input,” “write,” and “read” operations and used to create genetic “logic-and-memory” circuits, as well as “sample-and-hold” circuits.

Conclusion: SCRIBE is a scalable platform that uses genomic DNA for analog, rewritable, and flexible memory distributed across living cell populations. The scientists anticipate that SCRIBE will enable long-term cellular recorders for environmental and biomedical applications. Future optimization of recombination efficiencies achievable by SCRIBE could lead to more efficient single-cell digital memories and enhanced genome engineering technologies. Furthermore, the ability to regulate the generation of arbitrary targeted mutations with other gene-editing technologies should enable genomically encoded memory in additional organisms.
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Graphene Nanopores with Optical Antennas for Direct Optical DNA Sequencing

Graphene Nanopores with Optical Antennas for Direct Optical DNA Sequencing | Amazing Science | Scoop.it

High-speed reading of the genetic code should get a boost with the creation of the world’s first graphene nanopores – pores measuring approximately 2 nanometers in diameter – that feature a “built-in” optical antenna. Researchers with Berkeley Lab and the University of California (UC) Berkeley have invented a simple, one-step process for producing these nanopores in a graphene membrane using the photothermal properties of gold nanorods.

“With our integrated graphene nanopore with plasmonic optical antenna, we can obtain direct optical DNA sequence detection,” says Luke Lee, the Arnold and Barbara Silverman Distinguished Professor at UC Berkeley. Lee and Alex Zettl, a physicist who holds joint appointments with Berkeley Lab’s Materials Sciences Division and UC Berkeley’s Physics Department, were the leaders of a study in which a hot spot on a graphene membrane formed a nanopore with a self-integrated optical antenna. The hot spot was created by photon-to-heat conversion of a gold nanorod.


“We believe our approach opens new avenues for simultaneous electrical and optical nanopore DNA sequencing and for regulating DNA translocation,” says Zettl, who is also a member of the Kavli Energy Nanoscience Institute (Kavli ENSI).

Nanopore sequencing of DNA, in which DNA strands are threaded through nanoscale pores and read one letter at a time, has been touted for its ability to make DNA sequencing a faster and more routine procedure. Under today’s technology, the DNA letters are “read” by an electrical current passing through nanopores fabricated on a silicon chip. Trying to read electrical signals from DNA passing through thousands of nanopores at once, however, can result in major bottlenecks. Adding an optical component to this readout would help eliminate such bottlenecks

“Direct and enhanced optical signals are obtained at the junction of a nanopore and its optical antenna,” says Lee. “Simultaneously correlating this optical signal with the electrical signal from conventional nanopore sequencing provides an added dimension that would be an enormous advantage for high-throughput DNA readout.”

A key to the success of this effort is the single-step photothermal mechanism that enables the creation of graphene nanopores with self-aligned plasmonic optical antennas. The dimensions of the nanopores and the optical characteristics of the plasmonic antenna are tunable, with the antenna functioning as both optical signal transducer and enhancer. The atomically thin nature of the graphene membrane makes it ideal for high resolution, high throughput, single-molecule DNA sequencing. DNA molecules can be labeled with fluorescent dyes so that each base-pair fluoresces at a signature intensity as it passes through the junction of the nanopore and its optical antenna.

“In addition, either the gold nanoplasmonic optical antenna or the graphene can be functionalized to be responsive to different base-pair combinations,” Lee says. “The gold plasmonic optical antenna can also be functionalized to enable the direct optical detection of RNA, proteins, protein-protein interactions, DNA-protein interactions, and other biological systems.”

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Sequenced genomes reveal mutations that disable single genes and can help to identify new drugs

Sequenced genomes reveal mutations that disable single genes and can help to identify new drugs | Amazing Science | Scoop.it
On average, every person carries mutations that inactivate at least one copy of 200 or so genes and both copies of around 20 genes. However, knockout mutations in any particular gene are rare, so very large populations are needed to study their effects. These ‘loss of function’ mutations have long been implicated in certain debilitating diseases, such as cystic fibrosis. Most, however, seem to be harmless — and some are even beneficial to the persons carrying them. “These are people we’re not going to find in a clinic, but they’re still really informative in biology,” says MacArthur.

His group and others had been focusing on genome data, but they are now also starting to mine patient-health records to determine the — sometimes subtle — effects of the mutations. In a study of more than 36,000 Finnish people, published in July (E. T. Lim et al. PLoS Genet. 10, e1004494; 2014), MacArthur and his team discovered that people lacking a gene called LPA might be protected from heart disease, and that another knockout mutation, carried in one copy of a gene by up to 2.4% of Finns, may cause fetuses to miscarry if it is present in both copies.

Bing Yu of the University of Texas Health Science Center in Houston told the meeting how he and his collaborators had compared knockout mutations found in more than 1,300 people with measurements of around 300 molecules in their blood. The team found that mutations in one gene, called SLCO1B1, were linked to high levels of fatty acids, a known risk factor for heart failure. And a team from the Wellcome Trust Sanger Institute in Hinxton, UK, reported that 43 genes whose inactivation is lethal to mice were found to be inactivated in humans who are alive and apparently well.


The poster child for human-knockout efforts is a new class of drugs that block a gene known as PCSK9 (see Nature 496, 152–155; 2013). The gene was discovered in French families with extremely high cholesterol levels in the early 2000s. But researchers soon found that people with rare mutations that inactivate one copy of PCSK9 have low cholesterol and rarely develop heart disease. The first PCSK9-blocking drugs should hit pharmacies next year, with manufacturers jostling for a share of a market that could reach US$25 billion in five years.


“I think there are hundreds more stories like PCSK9 out there, maybe even thousands,” in which a drug can mimic an advantageous loss-of-function mutation, says Eric Topol, director of the Scripps Translational Science Institute in La Jolla, California. Mark Gerstein, a bio­informatician at Yale University in New Haven, Connecticut, predicts that human knockouts will be especially useful for identifying drugs that treat diseases of ageing. “You could imagine there’s a gene that is beneficial to you as a 25-year-old, but the thing is not doing a good job for you when you’re 75.”

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High-speed evolution in the lab: Geneticists evaluate cost-effective pool genome analysis

High-speed evolution in the lab: Geneticists evaluate cost-effective pool genome analysis | Amazing Science | Scoop.it

Life implies change. And this holds true for genes as well. Organisms require a flexible genome in order to adapt to changes in the local environment. Christian Schlötterer and his team from the Institute for Population Genetics at the University of Veterinary Medicine, Vienna study the genomes of entire populations. The scientists want to know why individuals differ from each other and how these differences are encoded in the DNA. In two review papers published in the journals Nature Reviews Genetics and Heredity, they discuss why DNA sequencing of entire groups can be an efficient and cost-effective way to answer these questions.   

DNA analysis has become increasingly efficient and cost-effective since the human genome was first fully sequenced in the year 2001. Sequencing a complete genome, however, still costs around US$1,000. Sequencing the genetic code of hundreds of individuals would therefore be very expensive and time-consuming. In particular for non-human studies, researchers very quickly hit the limit of financial feasibility.  

The solution to this problem is pool sequencing (Pool-Seq). Schlötterer and his team sequence entire groups of fruit flies (Drosophila melanogaster) at once instead of carrying out many individual sequencing reactions. While the resulting genetic information cannot be attributed to a single individual, the complete data set still provides important genetic information about the entire population.


In order to understand how organisms react to changes in the local environment, the genomes of entire populations can be analysed using Pool-Seq, before and after changed conditions. To do so, the researchers use the method of evolve and resequence (E&R). Schlötterer received an ERC Advanced Grant for this approach in 2012. E&R is a method in which the DNA of a group of individuals is sequenced.  After exposing the descendents of this group for several generations to a certain stress, such as high temperature, extreme cold or UV radiation, and the evolved group is then sequenced again. A comparison of the two data sets uncovers genes that have changed in response to the selective stress. The approach makes it possible, for example, to filter out the genes that are involved in a darker pigmentation in response to UV radiation. 


“Using this principle, we can perform evolution experiments at high speed. We are using this method to address a broad range of questions, ranging from the identification of genes which influence aging, or genes protecting against diseases and finally to understand the genetic changes which reduce the impact of climate change,” Schlötterer explains.

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Bacteria Make Drug-Like Molecules in Humans: Over 14,000 biosynthetic Gene Clusters for Small Molecules Identified

Bacteria Make Drug-Like Molecules in Humans: Over 14,000 biosynthetic Gene Clusters for Small Molecules Identified | Amazing Science | Scoop.it

Small molecules encoded by biosynthetic gene clusters are widely used in the clinic and constitute much of the chemical language of interspecies interactions. In a recent study, researchers used a systematic approach to identify more than 3,000 small-molecule biosynthetic gene clusters in the genomes of human-associated bacteria. As reported in Cell, they discovered that biosynthetic gene clusters for thiopeptides—a class of antibiotics—are widely distributed in the genomes of the human microbiota.


“This study shows for the first time that our microbiota—the good microbes that live with humans—produce drug-like molecules to protect us from pathogens,” said lead study author Mohamed Donia of the University of California, San Francisco (UCSF). “For a long time, scientists used to go to remote and exotic places to find bacteria that produce novel chemical entities with drug-like properties. Who knew we could find similar ones in our own bodies?”


Donia and his collaborators used an algorithm they recently developed to systematically analyze about 2,400 reference genomes of the human microbiota from various body sites. They detected more than 14,000 biosynthetic gene clusters for a broad range of small-molecule classes. Reasoning that the products of these gene clusters are most likely to mediate conserved microbe-host and microbe-microbe interactions, they set out to identify the subset of gene clusters commonly found in healthy individuals by analyzing 752 metagenomic samples from the National Institutes of Health Human Microbiome Project.


Remarkably, nearly all of these gene clusters had never before been studied or even described, illustrating how little is known about their small-molecule products. “We need to study every single one of these molecules and understand what they are doing,” Donia said. “We have published the list of the small molecule-encoding genes that we identified, and we are reaching out to the scientific community to help us characterize them.”


Thiopeptides are perhaps the most interesting of these molecules because they have potent antibacterial activity against Gram-positive species. Currently, one semisynthetic member of this class is undergoing clinical trials for treating bacterial infections. But according to the authors, no thiopeptide biosynthetic gene cluster or small-molecule product from the human microbiome had ever been experimentally characterized. Surprisingly, their analysis revealed thiopeptide-like biosynthetic gene clusters in isolates from every human body site.


Donia and his collaborators went on to purify and solve the structure of a thiopeptide named lactocillin, which showed potent antibacterial activity against a range of Gram-positive vaginal pathogens. By analyzing human metatranscriptomic sequencing data, they showed that lactocillin and other thiopeptide biosynthetic gene clusters were expressed in vivo, suggesting a potential role in mediating microbe-microbe interactions.

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Shang Zhuo's curator insight, October 25, 2014 9:04 AM

We can find antibiotics from our own body! It is really fascinating news. Perhaps the microbiota in our gut is a good source of bioactive molecules but is ignored by scientists for a long time.

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Rats! NYC rats infected with at least 18 new viruses, but no bubonic plague bacteria found

Rats! NYC rats infected with at least 18 new viruses, but no bubonic plague bacteria found | Amazing Science | Scoop.it

Rats: some people enjoy their company as pets, to many others, they are virulent pests that helped the spread of the bubonic plague ("black death") in Medieval Europe. For New Yorkers, they are just one of many interesting local daily sights on the subway tracks and platforms. I can tell you from experience (source: I live in New York City) that they often seem healthier and in better spirits than many of the humans that call this fair city home. Yet it turns out some of them are carrying a surprising number of previously undocumented viruses, according to the results of a study of the Big Apple's rodents published today in the journal mBio and reported by The New York Times.


Specifically, scientists captured 133 rats from traps set in five locations around New York City, euthanized them, then took genetic samples of the bacteria and viral specimens found in their tissues and excretions (saliva, feces, etc). The scientists found lots of viruses, not surprisingly. But while many of the bacteria detected were expected — including e. coli and salmonella — the scientists also found at 18 completely new viruses. None of these new viruses have been found in humans, at least not yet, but two of them are structurally similar to Hepatitis C, which does occur in people and raises the risk of liver scarring and cancer. While there's no immediate cause for alarm, the scientists note that that the spread of these new viruses from rats to humans could theoretically already be occurring and is possible in the future, and are advocating for more comprehensive disease monitoring in humans. Something to think about the next time you're waiting for the downtown F train.

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Illumina Says 228,000 Human Genomes Will Be Sequenced in 2014

Illumina Says 228,000 Human Genomes Will Be Sequenced in 2014 | Amazing Science | Scoop.it

Henry Ford kept lowering the price of cars, and more people kept buying them. The San Diego–based gene sequencing company Illumina has been doing something similar with the tools needed to interpret the human genetic code.


A record 228,000 human genomes will be completely sequenced this year by researchers around the globe, said Francis de Souza, president of Illumina, the maker of machines for DNA sequencing, during MIT Technology Review’s EmTech conference in Cambridge, Massachusetts.

De Souza said Illumina’s estimates suggest that the number will continue to double about every 12 months, reaching 1.6 million genomes by 2017, as the technology shifts from a phase of collapsing prices to expanding use in medicine.


The price of sequencing a single genome has dropped from the $3 billion spent by the original Human Genome Project 13 years ago to as little as $1,000, he said.


During an interview, De Souza questioned whether the price would keep falling at that rate. “It’s not clear you can get another order of magnitude out of this,” he said. Instead, he said, his company’s focus is now on making DNA studies more widespread in hospitals, police labs, and other industries.


“The bottleneck now is not the cost—it’s going from a sample to an answer,” De Souza said. “People are saying the price is not the issue.”

Illumina’s sequencing machines, which cost as much as $1 million each, are unmatched in their speed and accuracy. But the company’s growth has rested sometimes precariously on two curves. One has been the collapsing price of sequencing. The other is the soaring demand from genome scientists and funding agencies.


During the EmTech conference, De Souza said Illumina’s success was due to a “hard pivot” the company made in 2006, when it got into the DNA sequencing business by acquiring Solexa, a U.K. startup, and bet its fortunes “on a technology with no sales, that no one knew if it would work.”


That bet succeeded spectacularly, with Illumina machines now accounting for more than 90 percent of all DNA data produced. Last year, Illumina sold $1.4 billion worth of equipment, chemicals, and tests, about 25 percent more than the year before.


But De Souza says Illumina is now pivoting again. This time, its big bet is that DNA sequencing will become routine in medicine, not just in research labs. To make sure that happens, he said, the company is investing in simplifying its technology, winning FDA approval for more diagnostic tests doctors could order directly, developing ways to store DNA data in the cloud, and even launching a DNA app store. “The big pivot now is to the clinic. Getting there will change everything that we do,” he said.


For now, most DNA sequencing is still done by science labs. Of the 228,000 genomes Illumina estimates will be sequenced this year, more than 80 percent are part of scientific research projects, De Souza said. Those include a plan that the U.K.’s government is undertaking to decode 100,000 genomes over several years.

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“Deadly diarrhea” rates in US hospitals nearly doubled in last 10 years, study shows

“Deadly diarrhea” rates in US hospitals nearly doubled in last 10 years, study shows | Amazing Science | Scoop.it

Infections with the intestinal superbug C. difficile nearly doubled from 2001 to 2010 in U.S. hospitals without noticeable improvement in patient mortality rates or hospital lengths of stay, according to a study of 2.2 million C. difficile infection (CDI) cases published in the October issue of the American Journal of Infection Control, the official publication of the Association for Professionals in Infection Control and Epidemiology (APIC).


 In this retrospective study from The University ofTexas College of Pharmacy, researchers analyzed 10 years of data from the U.S. National Hospital Discharge Surveys (NHDS). From 2001 to 2010, rates of CDI among hospitalized adults rose from 4.5 to 8.2 CDI discharges per 1,000 total adult hospital discharges.

 

"Several factors may have contributed to the rise inCDI incidence in recent years," said Kelly Reveles, PharmD, PhD, lead author on the study. "Antibiotic exposure remains the most important risk factor forCDI." 


According to the Centers for Disease Control and Prevention (CDC)C. difficile is the most common bacteria responsible for causing healthcare-associated infections in U.S. hospitals and is linked to 14,000 deaths each year. Reducing the use of high-risk, broad-spectrum antibiotics by 30 percent could lower CDI by 26 percent, estimates the CDC. The White House recently announced a new Executive Order and National Strategy for Combating Antibiotic-resistant Bacteria, which emphasized the need for antibiotic stewardship programs to help clinicians improve prescribing practices.


"It's been estimated that up to half of antibiotic used in humans is unnecessary," said APIC 2014 President Jennie Mayfield, BSN, MPH,CIC. "To make headway against CDI, hospitals and health facilities need to get serious about antibiotic stewardship."


According to The University of Texas College of Pharmacy study, most CDI patients were female (59 percent), white (86 percent), and more than 65 years of age (70 percent).  


Of the 2.2 million adult CDI discharges, 33 percent had a principal diagnosis of CDI; 67 percent were classified as secondary CDI, meaning that CDI was not the primary reason they were hospitalized. Approximately 7.1 percent, or 154,184 patients, died during the study period.

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First complete sequence of C. autoethanogenum, a bacteria important to fuel and chemical production

First complete sequence of C. autoethanogenum, a bacteria important to fuel and chemical production | Amazing Science | Scoop.it
Researchers at the Department of Energy’s Oak Ridge National Laboratory are the first team to sequence the entire genome of the Clostridium autoethanogenum bacterium, which is used to sustainably produce fuel and chemicals from a range of raw materials, including gases derived from biomass and industrial wastes.

The ORNL work was funded by LanzaTech, a biotechnology company based in Illinois with an innovative carbon recycling process. LanzaTech’s gas fermentation platform uses proprietary microbes for efficiently converting carbon-rich waste gases and residues into useful fuels and chemicals.

Successfully sequencing Clostridium autoethanogenum—classified as a complex, class III microbe because of its many repeating units of DNA bases—has been of significant interest to the biotechnology industry. A Biotechnology for Biofuels paper co-authored by ORNL’s Steve Brown and Miriam Land, University of Tennessee doctoral student Sagar Utturkar and collaborating LanzaTech researchers generated a top-5-percent rating from Altmetric, an online rating system that measures the volume and value of recognition an article receives from research communities and media outlets.

“With the complete genomic sequence, we will have a better understanding of the microbe’s metabolism and mutations that will enable LanzaTech to make modifications to the wild-type, or naturally occurring, strain for optimizing the conversion of waste into fuel,” Brown said. “Our ORNL lab has a lot of experience sequencing genomes, and we have the analytic capability to tackle this project.”

The research team sequenced the more than 4.3 million base pairs of DNA that make up the organism’s genome using RS-II long-read sequencing technology developed by Pacific Biosciences (PacBio).
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Genomic parasites like transposons and jumping genes become more active as mice age

Genomic parasites like transposons and jumping genes become more active as mice age | Amazing Science | Scoop.it

Probably all higher organisms, including humans, have parasitic DNA fragments called "jumping genes" that insert themselves into DNA molecules, disrupting genetic instructions in the process. And that phenomenon can result in age-related diseases such as cancer. But researchers at the University of Rochester now report that the "jumping genes" in mice become active as the mice age when a multi-function protein stops keeping them in check in order to take on another role.


In a study published today in Nature Communications, Professor of Biology Vera Gorbunova and Assistant Professor of Biology Andrei Seluanov explain that a protein called Sirt6 is needed to keep the jumping genes -- technically known as retrotransposons -- inactive. That's an entirely different function from the ones scientists had long associated with Sirt6, such as the repairing of broken DNA molecules and regulating metabolism.


"About half of the human genome is made up of retrotransposons," said Gorbunova. "By better understanding why these genomic parasites become active, we hope to better understand and perhaps delay the aging process in humans." For the most part, retrotransposons remain silent and inactive in organisms' genomes. But once they do become active, these DNA fragments can duplicate themselves and "jump" to new areas of the genome, disrupting the function of another gene by landing in an important part of the gene and changing its DNA sequence information.


But what happens to the Sirt6 proteins that kept the jumping genes inactive in younger cells? The answer lies in the role that Sirt6 plays in repairing DNA damage. Cells accumulate a lot of DNA damage over time that needs to be constantly repaired. As cells get older, Sirt6 becomes busier in taking care of the DNA damage. Gorbunova and Seluanov hypothesized that Sirt6 becomes so preoccupied in repairing DNA damage in older cells that it is no longer available to keep the jumping genes inactive.


To test the theory, the team artificially caused DNA damage in young cells using gamma radiation or the chemical hydrogen peroxide. Once the damage took place, Sirt6 was immediately recruited to the damaged sites of the DNA to do its repair work. Gorbunova and Seluanov found that the stressed cells -- the ones with increased DNA damage -- had a higher rate of "jumping gene" activity, when compared to the other cells. Then, when the amount of Sirt6 was artificially increased in the stressed cells, the retrotransposons did not become as readily active, keeping the genome safe.


"This suggests that supplying more Sirt6 protein might protect older cells from aging," said Gorbunova. "The idea would be to increase the Sirt6 pool so that enough proteins are available for both DNA repair and for keeping the retrotransposons inactive.


Reference:

  1. Michael Van Meter, Mehr Kashyap, Sarallah Rezazadeh, Anthony J. Geneva, Timothy D. Morello, Andrei Seluanov, Vera Gorbunova. SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and ageNature Communications, 2014; 5: 5011 DOI: 10.1038/ncomms6011
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European gene pools seems to be derived from three ancient populations

European gene pools seems to be derived from three ancient populations | Amazing Science | Scoop.it

The modern European gene pool was formed when three ancient populations mixed within the last 7,000 years, Nature reports.


Blue-eyed, swarthy hunters mingled with brown-eyed, pale skinned farmers as the latter swept into Europe from the Near East. But another, mysterious population with Siberian affinities also contributed to the genetic landscape of the continent. The findings are based on analysis of genomes from nine ancient Europeans. Agriculture originated in the Near East - in modern Syria, Iraq and Israel - before expanding into Europe around 7,500 years ago.


Multiple lines of evidence suggested this new way of life was spread by a wave of migrants, who interbred with the indigenous European hunter-gatherers they encountered on the way. But assumptions about European origins were based largely on the genetic patterns of living people. The science of analysing genomic DNA from ancient bones has put some of the prevailing theories to the test, throwing up a few surprises.


In the new paper, Prof David Reich from the Harvard Medical School and colleagues studied the genomes of seven hunter-gatherers from Scandinavia, one hunter whose remains were found in a cave in Luxembourg and an early farmer from Stuttgart, Germany. The hunters arrived in Europe thousands of years before the advent of agriculture, hunkered down in southern refuges during the Ice Age and then expanded during a period called the Mesolithic, after the ice sheets had retreated from central and northern Europe.


Their genetic profile is not a good match for any modern group of people, suggesting they were caught up in the farming wave of advance. However, their genes live on in modern Europeans, to a greater extent in the north-east than in the south.


The early farmer genome showed a completely different pattern, however. Her genetic profile was a good match for modern people in Sardinia, and was rather different from the indigenous hunters.

But, puzzlingly, while the early farmers share genetic similarities with Near Eastern people at a global level, they are significantly different in other ways. Prof Reich suggests that more recent migrations in the farmers' "homeland" may have diluted their genetic signal in that region today.


Prof Reich explained: "The only way we'll be able to prove this is by getting ancient DNA samples along the potential trail from the Near East to Europe... and seeing if they genetically match these predictions or if they're different.


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Oxytricha trifallax breaks its own DNA into a quarter-million pieces and rapidly reassemble those for mating

Oxytricha trifallax breaks its own DNA into a quarter-million pieces and rapidly reassemble those for mating | Amazing Science | Scoop.it

Life can be so intricate and novel that even a single cell can pack a few surprises, according to a study led by Princeton University researchers. The pond-dwelling, single-celled organism Oxytricha trifallax has the remarkable ability to break its own DNA into nearly a quarter-million pieces and rapidly reassemble those pieces when it's time to mate, the researchers report in the journal Cell.


The organism internally stores its genome as thousands of scrambled, encrypted gene pieces. Upon mating with another of its kind, the organism rummages through these jumbled genes and DNA segments to piece together more than 225,000 tiny strands of DNA. This all happens in about 60 hours.


The organism's ability to take apart and quickly reassemble its own genes is unusually elaborate for any form of life, explained senior author Laura Landweber, a Princeton professor of ecology and evolutionary biology. That such intricacy exists in a seemingly simple organism accentuates the "true diversity of life on our planet," she said.


"It's one of nature's early attempts to become more complex despite staying small in the sense of being unicellular," Landweber said. "There are other examples of genomic jigsaw puzzles, but this one is a leader in terms of complexity. People might think that pond-dwelling organisms would be simple, but this shows how complex life can be, that it can reassemble all the building blocks of chromosomes."


From a practical standpoint, Oxytricha is a model organism that could provide a template for understanding how chromosomes in more complex animals such as humans break apart and reassemble, as can happen during the onset of cancer, Landweber said. While chromosome dynamics in cancer cells can be unpredictable and chaotic, Oxytricha presents an orderly step-by-step model of chromosome reconstruction, she said.


"It's basically bad when human chromosomes break apart and reassemble in a different order," Landweber said. "The process in Oxytricha recruits some of the same biological mechanisms that normally protect chromosomes from falling apart and uses them to do something creative and constructive instead."


Gertraud Burger, a professor of biochemistry at the University of Montreal, said that the "rampant and diligently orchestrated genome rearrangements that take place in this organism" demonstrate a unique layer of complexity for scientists to consider when it comes to studying an organism's genetics.


"This work illustrates in an impressive way that the genetic information of an organism can undergo substantial change before it is actually used for building the components of a living cell," said Burger, who is familiar with the work but had no role in it.


"Therefore, inferring an organism's make-up from the genome sequence alone can be a daunting task and maybe even impossible in certain instances," Burger said. "A few cases of minor rearrangements have been described in earlier work, but these are dilettantes compared to [this] system."

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Coffee Genome Sequenced and Annotated

Coffee Genome Sequenced and Annotated | Amazing Science | Scoop.it

The coffee genome has been sequenced for the first time, brewing up a better understanding of that flavor, aroma, and buzz we love (and need) so much. According to the findings, published in Science this week, the caffeine-producing enzymes in coffee evolved independently from those in tea and chocolate. 


“The coffee genome helps us understand what’s exciting about coffee -- other than that it wakes me up in the morning,” says SUNY Buffalo’s Victor Albert in a news release. “By looking at which families of genes expanded in the plant, and the relationship between the genome structure of coffee and other species, we were able to learn about coffee’s independent pathway in evolution, including -- excitingly -- the story of caffeine.”


Commonly known as robusta coffee, Coffea canephora makes up 30 percent of the coffee produced worldwide -- which totals 8.7 million tons a year or 2.25 billion cups a day. The less acidic-tasting Coffea arabica makes up most of the rest, but this lower caffeine variety has a more complicated genome. 


So, to derive a draft genome of Coffea canephora, a huge consortium led by Albert and researchers from the French Institute of Research for Development and the French National Sequencing Center pieced together DNA sequences and assembled a total length of 568.6 megabases -- that’s 80 percent of the plant’s 710-megabase genome.


After running a comparative genomics software on protein sequences from coffee, grape, tomato, and a flowering plant called Arabidopsis, the team identified 16,000 genes that originated from a single gene in their last common ancestor. They were also able to pinpoint adaptations in genes for disease resistance and caffeine production that were unique to coffee. Overall, the team isolated 25,574 protein-making genes in the Coffea canephora genome and 23 new genes that are only found in coffee.


The robusta coffee genome also revealed that the enzymes involved in coffee’s caffeine production -- called N-methyltransferases -- adapted independently from those in cacao and tea. That is, they didn’t inherit their caffeine-linked genes from a common ancestor: The ability to produce caffeine must have evolved at least twice, and long before we started depending on it.


But what good is caffeine for plants? It may protect the coffee plant from predators like leaf-eating bugs, and when their leaves fall on the ground, the high caffeine concentration stunts the growth of rival plants trying to develop near them. “Caffeine also habituates pollinators and makes them want to come back for more, which is what it does to us, too,”Albert tells Nature. Furthermore, over evolutionary time, the coffee genome wasn't triplicated or duplicated en masse. Instead, the team team thinks that the duplication of individual genes, including the caffeine ones, spurred innovations, Science explains.

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Whole-genome sequences of 17 of the world’s oldest living people published

Whole-genome sequences of 17 of the world’s oldest living people published | Amazing Science | Scoop.it

Using 17 genomes, researchers were unable to find rare protein-altering variants significantly associated with extreme longevity, according to a study published November 12, 2014 in the open-access journal PLOS ONE by Hinco Gierman from Stanford University and colleagues.


Supercentenarians are the world’s oldest people, living beyond 110 years of age. Seventy-four are alive worldwide; 22 live in the U.S. The authors of this study performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity.


From this small sample size, the researchers were unable to find rare protein-altering variants significantly associated with extreme longevity compared to control genomes. However, they did find that one supercentenarian carries a variant associated with a heart condition, which had little or no effect on his/her health, as this person lived over 110 years.


Although the authors didn’t find significant association with extreme longevity, the authors have publicly published the genomes, making them available as a resource for future studies on the genetic basis of extreme longevity.


Reference:

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Deep Sequencing Identifies Noncanonical Editing of Ebola and Marburg Virus RNAs in Infected Cells

Deep Sequencing Identifies Noncanonical Editing of Ebola and Marburg Virus RNAs in Infected Cells | Amazing Science | Scoop.it

Deep sequencing of RNAs produced by Zaire ebolavirus (EBOV) or the Angola strain of Marburgvirus (MARV-Ang) identified novel viral and cellular mechanisms that diversify the coding and noncoding sequences of viral mRNAs and genomic RNAs. A team of scientists now identified previously undescribed sites within the EBOV and MARV-Ang mRNAs where apparent co-transcriptional editing has resulted in the addition of non-template-encoded residues within the EBOV glycoprotein (GP) mRNA, the MARV-Ang nucleoprotein (NP) mRNA, and the MARV-Ang polymerase (L) mRNA, such that novel viral translation products could be produced. Further, they found that the well-characterized EBOV GP mRNA editing site is modified at a high frequency during viral genome RNA replication. Additionally, editing hot spots representing sites of apparent adenosine deaminase activity were found in the MARV-Ang NP 3′-untranslated region. These studies identify novel filovirus-host interactions and reveal production of a greater diversity of filoviral gene products than was previously appreciated.


This study identifies novel mechanisms that alter the protein coding capacities of Ebola and Marburg virus mRNAs. Therefore, filovirus gene expression is more complex and diverse than previously recognized. These observations suggest new directions in understanding the regulation of filovirus gene expression.

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Fact or Fiction?: Mammoths Can Be Brought Back from Extinction

Fact or Fiction?: Mammoths Can Be Brought Back from Extinction | Amazing Science | Scoop.it

In a petri dish in the bowels of Harvard Medical School scientists have tweaked three genes from the cells of an Asian elephant that help control the production of hemoglobin, the protein in blood that carries oxygen. Their goal is to make these genes more like those of an animal that last walked the planet thousands of years ago: the woolly mammoth.

"Asian elephants are closer to mammoths than either is to African elephants, yet quite different in appearance and temperature range," notes Harvard geneticist and technology developer George Church. "We are not trying to make an exact copy of a mammoth, but rather a cold-resistant elephant."
 
But what if the new—and fast advancing—techniques of genome editing allowed scientists to engineer not only cold-resistance traits but also other characteristics of the woolly mammoth into its living Asiatic relatives? Scientists have found mammoth cells preserved in permafrost. If they were to recover cells with intact DNA, they could theoretically “edit” an Asian elephant’s genome to match the woolly mammoth’s. A single cell contains the complete genetic instruction set for its species, and by replicating that via editing a new individual can, theoretically, be created. But wouldsuch a hybrid—scion of an Asian elephant mother and genetic tinkerers—count as a true woolly mammoth?
 
In other words, is de-extinction a real possibility?
 
The answer is yes. On January 6, 2000, a falling tree killed the last bucardo, a wild Iberian ibex, which is a goatlike animal. Her name was Celia. On July 30, 2003, Celia's clone was born. To make the clone scientists removed the nucleus of a cell from Celia intact and inserted it into the unfertilized egg cell of another kind of ibex. They then transferred the resulting embryo to the womb of a living goat. Nearly a year later theydelivered the clone by cutting her from her mother.
 
Although she lived for a scant seven minutes due to lung defects, Celia’s clone proved that not only is de-extinction real, "it has already happened," in the words of environmentalist Stewart Brand, whose San Francisco-based Long Now Foundation is funding some of this de-extinction research, including Church's effort as well as bids to bring back the passenger pigeon and heath hen, among other candidate species. Nor is the bucardo alone in the annals of de-extinction. Several viruses have already been brought back, including the flu variant responsible for the 1918 pandemic that killed more than 20 million people worldwide.

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Siberian thighbone data adjust time of human and Neanderthal interbreeding to around 50,000 years ago

Siberian thighbone data adjust time of human and Neanderthal interbreeding to around 50,000 years ago | Amazing Science | Scoop.it

New research on a 45,000-year-old Siberian thighbone has narrowed the window of time when humans and Neanderthals interbred to between 50,000 and 60,000 years ago, and has shown that modern humans reached northern Eurasia substantially earlier than some scientists thought.


Qiaomei Fu, a postdoctoral fellow at Harvard Medical School (HMS) and first author of a paper describing the research, said the sample had a long history before making its way into her hands.


The bone was found eroding out of a Siberian riverbank, but no one knows precisely where. The bone changed hands several times before finding its way to the Max Planck Institute for Evolutionary Anthropology in Germany, where Fu was working with professors Janet Kelso and Svante Pääbo. Fu put the finishing touches on the research after she started in the laboratory of David Reich, HMS genetics professor.


Carbon dating and molecular analysis filled in many of the blanks about the sample. Testing determined that the sample was from an individual who lived 45,000 years ago on a diet that included plants or plant eaters and fish or other aquatic life.


Reich and Fu said the sample was remarkable because of the extraordinary preservation of its DNA, which allowed Fu, using the latest techniques for ancient DNA analysis, to extract a high-quality genome sequence. The sequence, Reich said, is significantly higher in quality than most genome sequences of present-day people generated for analysis of disease risk.


The sequence revealed that the bone came from a modern human, a man whose remains are the oldest ever found and carbon-dated outside of Africa and the Middle East. Comparison to diverse humans around the world today showed that the man was a member of one of the most ancient non-African populations.


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Geneticist George Church: A Future Without Limits

Geneticist George Church: A Future Without Limits | Amazing Science | Scoop.it

In the future, George Church believes, almost everything will be better because of genetics. If you have a medical problem, your doctor will be able to customize a treatment based on your specific DNA pattern. When you fill up your car, you won't be draining the world's dwindling supply of crude oil, because the fuel will come from microbes that have been genetically altered to produce biofuel. When you visit the zoo, you'll be able to take your children to the woolly mammoth or passenger pigeon exhibits, because these animals will no longer be extinct. You'll be able to do these things, that is, if the future turns out the way Church envisions it—and he's doing everything he can to see that it does.


In 2005 he launched the Personal Genome Project, with the goal of sequencing and sharing the DNA of 100,000 volunteers. With an open-source database of that size, he believes, researchers everywhere will be able to meaningfully pursue the critical task of correlating genetic patterns with physical traits, illnesses, and exposure to environmental factors to find new cures for diseases and to gain basic insights into what makes each of us the way we are. Church, tagged as subject hu43860C, was first in line for testing. Since then, more than 13,000 people in the U.S., Canada, and the U.K. have volunteered to join him, helping to establish what he playfully calls the Facebook of DNA.


Church has made a career of defying the impossible. Propelled by the dizzying speed of technological advancement since then, the Personal Genome Project is just one of Church's many attempts to overcome obstacles standing between him and the future.


"It's not for everyone," he says. "But I see a trend here. Openness has changed since many of us were young. People didn't use to talk about sexuality or cancer in polite society. This is the Facebook generation." If individuals were told which diseases or medical conditions they were genetically predisposed to, they could adjust their behavior accordingly, he reasoned. Although universal testing still isn't practical today, the cost of sequencing an individual genome has dropped dramatically in recent years, from about $7 million in 2007 to as little as $1,000 today.


"It's all too easy to dismiss the future," he says. "People confuse what's impossible today with what's impossible tomorrow.", especially through the emerging discipline of "synthetic" biology. The basic idea behind synthetic biology, he explained, was that natural organisms could be reprogrammed to do things they wouldn't normally do, things that might be useful to people. In pursuit of this, researchers had learned not only how to read the genetic code of organisms but also how to write new code and insert it into organisms. Besides making plastic, microbes altered in this way had produced carpet fibers, treated wastewater, generated electricity, manufactured jet fuel, created hemoglobin, and fabricated new drugs. But this was only the tip of the iceberg, Church wrote. The same technique could also be used on people.


"Every cell in our body, whether it's a bacterial cell or a human cell, has a genome," he says. "You can extract that genome—it's kind of like a linear tape—and you can read it by a variety of methods. Similarly, like a string of letters that you can read, you can also change it. You can write, you can edit it, and then you can put it back in the cell."


This April, the Broad Institute, where Church holds a faculty appointment, was awarded a patent for a new method of genome editing called CRISPR (clustered regularly interspersed short palindromic repeats), which Church says is one of the most effective tools ever developed for synthetic biology. By studying the way that certain bacteria defend themselves against viruses, researchers figured out how to precisely cut DNA at any location on the genome and insert new material there to alter its function. Last month, researchers at MIT announced they had used CRISPR to cure mice of a rare liver disease that also afflicts humans. At the same time, researchers at Virginia Tech said they were experimenting on plants with CRISPR to control salt tolerance, improve crop yield, and create resistance to pathogens.


The possibilities for CRISPR technology seem almost limitless, Church says. If researchers have stored a genetic sequence in a computer, they can order a robot to produce a piece of DNA from the data. That piece can then be put into a cell to change the genome. Church believes that CRISPR is so promising that last year he co-founded a genome-editing company, Editas, to develop drugs for currently incurable diseases.

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Scientists identify more than 400 genetic regions that influence height

Scientists identify more than 400 genetic regions that influence height | Amazing Science | Scoop.it

The researchers say their findings, reached by analyzing genome-wide data from more than 250,000 people, can explain around 20% of height heritability in humans, increasing from 12% prior to this study.


"The study also narrows down the genomic regions that contain a substantial proportion of remaining variation - to be discovered with even larger sample sizes," says co-senior investigator Peter Visscher, PhD, of the University of Queensland in Australia.


The researchers publish their findings in the journal Nature Genetics.


Height is a model characteristic for determining the mechanisms behind human genetics, according to the investigators. It particularly helps improve understanding of traits that are produced by multiple genes. They note that height is simple to measure, and approximately 80% of height variation is genetic. The remaining 20% is thought to be influenced by environmental and lifestyle factors.


Previous studies have suggested that height is influenced by lots of genes, most of which come from common genetic variants rather than rare ones. But the investigators involved in this latest research say that these studies have not been large enough to confirm such findings.

697 genetic variants in 424 genetic regions linked to height

With this in mind, the researchers set up the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. This involved analyzing the genomic data of 253,288 individuals from more than 300 worldwide institutions.


The team searched approximately 2 million genetic variants that were present in at least 5% of participants. From this, they identified 697 genetic variants located in 424 genetic regions that were linked to height.

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Soil ecologists confirm: Manhattan's Central Park is home to 170,000 different kinds of microbes

Soil ecologists confirm: Manhattan's Central Park is home to 170,000 different kinds of microbes | Amazing Science | Scoop.it
The urban oasis boasts about 170,000 different types of microbes, recent dirt samples show. That diversity is comparable to a tropical rain forest. About 2,000 species are found only in the park.


Manhattan's Central Park is surrounded by one of the densest cities on the planet. It's green enough, yet hardly the first place most people would think of as biologically rich.  But a team of scientists got a big surprise when they recently started digging there. They were 10 soil ecologists — Kelly Ramirez from Colorado State University was among them. "We met on the steps of the natural history museum at 7 a.m. with our collection gear, coolers and sunblock," she recalls.


Their goal: to collect about 600 soil samples from across the park and look for microbes. Why? Because Ramirez was the head of something called The Global Soil Biodiversity Initiative.


Given her love of dirt, Ramirez was the right person for the job. "I think soil biodiversity is like the stars beneath our feet," she says. "There is so much going on in the soil — it's just a hot spot, teeming with so many different types of organisms."


Microbes are architects of soil. They alter its chemistry, even its shape. And in terms of its microbes, Central Park was terra incognita. So the team fanned out and dug. Onlookers were — well, blasé. This was New York City. "I think because they're used to weird things going on in the park," says Ramirez, "it just probably looked sort of normal that we were collecting."


And what the team found turned out to be very surprising — almost 170,000 different kinds of microbes. They didn't expect an urban park to measure up to the wild places they'd sampled around the world. "There's as much biodiversity in the soils of Central Park as we found in the soil ... from the Arctic to Antarctica," says Ramirez, who's now at the Netherlands Institute of Ecology. She's including places like temperate forests, tropical forests and deserts. The species numbers are an average of all those places — some are a bit more or less diverse than Central Park. The team also found 2,000 species of microbes that are apparently unique to Central Park.

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Evolutionary arms race between retrotransposons and regulatory networks

Evolutionary arms race between retrotransposons and regulatory networks | Amazing Science | Scoop.it
Retrotransposons are thought to be remnants of ancient viruses that infected early animals and inserted their genes into the genome long before humans evolved. Now they can only replicate themselves within the genome. Depending on where a new copy gets inserted into the genome, a jumping event can disrupt normal genes and cause disease. Often the effect is neutral, simply adding to the overall size of the genome. Very rarely the effect might be advantageous, because the added DNA can itself be a source of new regulatory elements that enhance gene expression. But the high probability of deleterious effects means natural selection favors the evolution of mechanisms to prevent jumping events.

Scientists estimate that jumping genes or "transposable elements" account for at least 50 percent of the human genome, and retrotransposons are by far the most common type.

"There have been successive waves of retrotransposon activity in primate evolution, when a transposable element changed to become expressed and replicated itself throughout the genome until something turned it off," Salama said. "We've discovered a major mechanism by which the genome is able to shut down these mobile DNA elements."

The repressors identified in the new study belong to a large family of proteins known as "KRAB zinc finger proteins." These are DNA-binding proteins that repress gene activity, and they constitute the largest family of gene-regulating proteins in mammals. The human genome has over 400 genes for KRAB zinc finger proteins, and about 170 of them have emerged since primates diverged from other mammals.


Their findings, published September 28 in Nature, show that over evolutionary time, primate genomes have undergone repeated episodes in which mutations in jumping genes allowed them to escape repression, which drove the evolution of new repressor genes, and so on. Furthermore, their findings suggest that repressor genes that originally evolved to shut down jumping genes have since come to play other regulatory roles in the genome.


"We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about," said Sofie Salama, a research associate at the UC Santa Cruz Genomics Institute who led the study.

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All Ashkenazi Jews alive today can trace their roots to a group of just 350 people who lived 600 to 800 years ago

All Ashkenazi Jews alive today can trace their roots to a group of just 350 people who lived 600 to 800 years ago | Amazing Science | Scoop.it

Ashkenazi Jews (AJ), identified as Jewish individuals of Central- and Eastern European ancestry, form the largest genetic isolate in the United States. AJ demonstrate distinctive genetic characteristics12, including high prevalence of autosomal recessive diseases and relatively high frequency of alleles that confer a strong risk of common diseases, such as Parkinson’s disease3and breast and ovarian cancer4. Several recent studies have employed common polymorphisms5,-13 to characterize AJ as a genetically distinct population, close to other Jewish populations as well as to present-day Middle Eastern and European populations. Previous analyses of recent AJ history highlighted a narrow population bottleneck of only hundreds of individuals in late medieval times, followed by rapid expansion1214.


The AJ population is much larger and/or experienced a more severe bottleneck than other founder populations, such as Amish, Hutterites or Icelanders15, whose demographic histories facilitated a steady stream of genetic discoveries. This suggests the potential for cataloguing nearly all founder variants in a large extant population by sequencing a limited number of samples, who represent the diversity in the founding group (for example, ref. 16). Such a catalogue of variants can make a threefold contribution: First, it will enable clinical interpretation of personal genomes in the sizeable AJ population by distinguishing between background variation and recent, potentially more deleterious mutations. Second, it will improve disease mapping in AJ by increasing the accuracy of imputation. Third, the ability to extensively sample a population with ancient roots in the Levant is expected to provide insights regarding the histories of both Middle Eastern and European populations.


Now a team of scientists report high-depth sequencing of 128 complete genomes of AJ controls. Compared with European samples, our AJ panel has 47% more novel variants per genome and is eightfold more effective at filtering benign variants out of AJ clinical genomes. Reconstruction of recent AJ history from such data confirms a recent bottleneck of merely ≈350 individuals. Modeling of ancient histories for AJ and European populations using their joint allele frequency spectrum determines AJ to be an even admixture of European and likely Middle Eastern origins. The researchers date the split between the two ancestral populations to ≈12–25 Kyr, suggesting a predominantly Near Eastern source for the repopulation of Europe after the Last Glacial Maximum.

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Numerous viruses found living in and on the bodies of healthy humans

Numerous viruses found living in and on the bodies of healthy humans | Amazing Science | Scoop.it
Human herpesvirus 6, pictured above, is just one of numerous viruses found living in and on the bodies of healthy humans. The virus commonly causes illness in young children but is found in the mouths of some healthy young adults, where its presence indicates an active viral infection despite a lack of symptoms.


On average, healthy individuals carry about five types of viruses on their bodies, the researchers report online in BioMed Central Biology. The study is the first comprehensive analysis to describe the diversity of viruses in healthy people.


The research was conducted as part of the Human Microbiome Project, a major initiative funded by the National Institutes of Health (NIH) that largely has focused on cataloging the body's bacterial ecosystems. "Most everyone is familiar with the idea that a normal bacterial flora exists in the body," said study co-author Gregory Storch, MD, a virologist and chief of the Division of Pediatric Infectious Diseases. "Lots of people have asked whether there is a viral counterpart, and we haven't had a clear answer. But now we know there is a normal viral flora, and it's rich and complex."


In 102 healthy young adults ages 18 to 40, the researchers sampled up to five body habitats: nose, skin, mouth, stool and vagina. The study's subjects were nearly evenly split by gender. At least one virus was detected in 92 percent of the people sampled, and some individuals harbored 10 to 15 viruses.


"We were impressed by the number of viruses we found," said lead author Kristine M. Wylie, PhD, an instructor of pediatrics. "We only sampled up to five body sites in each person and would expect to see many more viruses if we had sampled the entire body."


Scientists led by George Weinstock, PhD, at Washington University's Genome Institute, sequenced the DNA of the viruses recovered from the body, finding that each individual had a distinct viral fingerprint. (Weinstock is now at The Jackson Laboratory in Connecticut.) About half of people were sampled at two or three points in time, and the researchers noted that some of the viruses established stable, low-level infections.


The researchers don't know yet whether the viruses have a positive or negative effect on overall health but speculate that in some cases, they may keep the immune system primed to respond to dangerous pathogens while in others, lingering viruses increase the risk of disease.

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Schizophrenia is not a single disease but rather consists of eight different genetically distinct classes

Schizophrenia is not a single disease but rather consists of eight different genetically distinct classes | Amazing Science | Scoop.it

New research shows that schizophrenia isn’t a single disease but a group of eight genetically distinct disorders, each with its own set of symptoms. The finding could be a first step toward improved diagnosis and treatment for the debilitating psychiatric illness.


The research at Washington University School of Medicine in St. Louis is reported online Sept. 15 in The American Journal of Psychiatry. About 80 percent of the risk for schizophrenia is known to be inherited, but scientists have struggled to identify specific genes for the condition.


Now, in a novel approach analyzing genetic influences on more than 4,000 people with schizophrenia, the research team has identified distinct gene clusters that contribute to eight different classes of schizophrenia.


“Genes don’t operate by themselves,” said C. Robert Cloninger, MD, PhD, one of the study’s senior investigators. “They function in concert much like an orchestra, and to understand how they’re working, you have to know not just who the members of the orchestra are but how they interact.” 

Cloninger, the Wallace Renard Professor of Psychiatry and Genetics, and his colleagues matched precise DNA variations in people with and without schizophrenia to symptoms in individual patients. In all, the researchers analyzed nearly 700,000 sites within the genome where a single unit of DNA is changed, often referred to as a single nucleotide polymorphism (SNP). They looked at SNPs in 4,200 people with schizophrenia and 3,800 healthy controls, learning how individual genetic variations interacted with each other to produce the illness. 

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Plant genomics: Methods for obtaining large, phylogenomic data sets

Plant genomics: Methods for obtaining large, phylogenomic data sets | Amazing Science | Scoop.it

The use of next-generation sequencing (NGS) technologies in phylogenetic studies is in a state of continual development and improvement. Though the botanically-inclined have historically focused on markers from the chloroplast genome, the importance of incorporating nuclear data is becoming increasingly evident. Nuclear genes provide not only the potential to resolve relationships between closely related taxa, but also the means to disentangle hybridization and better understand incongruences caused by incomplete lineage sorting and introgression.

By harnessing the power of NGS—which has increased sequencing capacity by several orders of magnitude over the past few years—scientists are now able to easily sequence enormous amounts of DNA or RNA from any genome within an organism, a practice that is transforming many areas of plant biology.


A team of international scientists, led by researchers at Oregon State University, has utilized a recently developed method to assemble a phylogenomic data set containing hundreds of nuclear loci and plastomes for milkweeds.


"This approach, termed Hyb-Seq, uses targeted sequence capture via hybridization-based enrichment and has shown great promise for obtaining large nuclear data sets," explains Dr. Aaron Liston, principal investigator of the study. "Sequencing low-copy nuclear genes has traditionally required a large amount of effort for each gene. Hyb-Seq eliminates the need for PCR optimization and cloning—two time-consuming and sometimes problematic steps."


The protocol is freely available in the September issue of Applications in Plant SciencesWhile it would be ideal to simply sequence entire genomes for every organism being studied, this is not yet feasible across large numbers of species. The Hyb-Seq approach reduces genomic complexity of the organism-of-interest by targeting only a small portion of the total genome. This is achieved by hybridizing DNA or RNA probes to specific regions of the genome, then simply discarding the remaining, unwanted regions.


"The probe design was done bioinformatically by comparing our draft sequence of the milkweed genome and transcriptome (expressed genes) to another genome in the same family and to genes that are conserved across the asterids and the angiosperms," explains Liston. "This allowed us to eliminate duplicated genes that can complicate phylogenetic inference and select relatively conserved genes, so that they could be obtained from divergent milkweed species with a single probe set."


This approach enabled Liston and colleagues to sequence over 700 genes for 10 Asclepias species and two related genera. "Furthermore," says Liston, "we were able to assemble complete plastomes from the off-target reads."


"It is likely that as sequencing technology advances, it will be feasible in the next decade or so to sequence complete genomes routinely and inexpensively. However, until that time, the ability to sequence hundreds of genes at a time—as is possible with the Hyb-Seq method—represents a significant and exciting advance over previous methods."

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