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Scooped by Dr. Stefan Gruenwald!

The Genomic Revolution Reaches Crime LabS

The Genomic Revolution Reaches Crime LabS | Amazing Science |
How will law enforcement handle the deluge of new information available from DNA?


Lisa Ziegert disappeared from the gift shop where she worked on April 15, 1992, and her body was found four days later. From then until this past Monday, her murder remained unsolved.

Then on Monday, the local district attorney’s office in


Massachusetts announced the arrest of a 48-year-old man for Ziegert’s death. Among the clues that led police to him was a computer-generated “mug shot” based on DNA found at the crime scene 25 years ago. Back then, the idea of predicting a face based on DNA would have seemed like science fiction. It is still rare today, but law-enforcement officials can quite easily order up such a test from the Virginia-based company Parabon NanoLabs.


Ziegert’s case is already being touted as an example of the power of new DNA technologies to solve crimes. In many ways, it’s the perfect example to take to the media: a young female victim, an infamous murder, a 25-year-old case. It’s unclear exactly how pivotal the DNA evidence was—the district attorney said “a number of factors” contributed to narrowing down the suspects—but there will almost certainly be more cases like this involving DNA.

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Large-scale Study of Genetic Data Shows Humans Still Evolving

Large-scale Study of Genetic Data Shows Humans Still Evolving | Amazing Science |

In a study analyzing the genomes of 210,000 people in the United States and Britain, Columbia researchers find that the genetic variants linked to Alzheimer’s disease and heavy smoking are less frequent in people with longer lifespans, suggesting that natural selection is weeding out these unfavorable variants in both populations.


Researchers further find that sets of genetic mutations that predispose people to early puberty and childbearing, heart disease, high cholesterol, obesity, and asthma, also appear less often in people who lived longer and whose genes are therefore more likely to be passed down and spread through the population. The results are published in the Sept. 5 issue of PLOS Biology.


“It’s a subtle signal, but we find genetic evidence that natural selection is happening in modern human populations,” said study coauthor Joseph Pickrell, an evolutionary geneticist at Columbia and New York Genome Center.


New favorable traits evolve when genetic mutations arise that offer a survival edge. As the survivors of each generation pass on those beneficial mutations, the mutations and their adaptive traits become more common in the general population. Though it may take millions of years for complex traits to evolve, say allowing humans to walk on two legs, evolution itself happens with each generation as adaptive mutations become more frequent in the population.


The genomic revolution has allowed biologists to see the natural selection process in action by making the genetic blueprint of hundreds of thousands of people available for comparison. By tracking the relative rise and fall of specific mutations across generations of people, researchers can infer which traits are spreading or dwindling.


The researchers analyzed the genomes of 60,000 people of European ancestry genotyped by Kaiser Permanente in California, and 150,000 people in Britain genotyped through the U.K. Biobank. To compensate for the relative lack of old people in the Biobank, the researchers used the participants’ parents age at death as a proxy as they looked for the influence of specific mutations on survival. 

Via Integrated DNA Technologies
Nevermore Sithole's curator insight, September 11, 2017 8:12 AM
Large-scale Study of Genetic Data Shows Humans Still Evolving
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Scientists Record and Replay Movie Encoded in DNA

Scientists Record and Replay Movie Encoded in DNA | Amazing Science |

For the first time, a primitive movie has been encoded in – and then played back from – DNA in living cells. Scientists funded by the National Institutes of Health say it is a major step toward a “molecular recorder” that may someday make it possible to get read-outs, for example, of the changing internal states of neurons as they develop.


“We want to turn cells into historians,” explained neuroscientist Seth Shipman, Ph.D. , a post-doctoral fellow at Harvard Medical School, Boston. “We envision a biological memory system that’s much smaller and more versatile than today’s technologies, which will track many events non-intrusively over time.”


Shipman, Harvard’s Drs. George Church , Jeffrey Macklis  andJeff Nivala  report on their proof-of-concept for a futuristic “molecular ticker tape” online July 12, in the journal Nature. The work was funded by NIH’s National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and the National Human Genome Research Institute.


The ability to record such sequential events like a movie at the molecular level is key to the idea of reinventing the very concept of recording using molecular engineering, say the researchers. In this scheme, cells themselves could be induced to record molecular events – such as changes in gene expression over time – in their own genomes. Then the information could be retrieved simply by sequencing the genomes of the cells it is stored in.


“If we had those transcriptional steps, we could potentially use them like a recipe to engineer similar cells,” added Shipman. “These could be used to model disease – or even in therapies.”


For starters, the researchers had to show that DNA can be used to encode not just genetic information, but any arbitrary sequential information into a genome. For this they turned to the cutting-edge, NIH-funded gene editing technology CRISPR . They first demonstrated that they could encode and retrieve an image of the human hand in DNA inserted into bacteria. They then similarly encoded and reconstructed frames from a classic 1870s race horse in motion  sequence of photos – an early forerunner of moving pictures.


The researchers had previously shown that they could use CRISPR to store sequences of DNA in bacteria. CRISPR is a group of proteins and DNA that act as an immune system in some bacteria, vaccinating them with genetic memories of viral infections. When a virus infects a bacterium, CRISPR cuts out part of the foreign DNA and stores it in the bacteria’s own genome. The bacterium then uses the stored DNA to recognize the virus and defend against future attacks. “The sequential nature of CRISPR makes it an appealing system for recording events over time,” explained Shipman.


The researchers then similarly translated five frames from the race horse in motion photo sequence into DNA. Over the course of five days, they sequentially treated bacteria with a frame of translated DNA. Afterwards, they were able to reconstruct the movie with 90 percent accuracy by sequencing the bacterial DNA.


Although this technology could be used in a variety of ways, the researchers ultimately hope to use it to study the brain. “We want to use neurons to record a molecular history of the brain through development,” said Shipman. “Such a molecular recorder will allow us to eventually collect data from every cell in the brain at once, without the need to gain access, to observe the cells directly, or disrupt the system to extract genetic material or proteins.”

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Germans provide big boost for sequencing often ignored organisms

Germans provide big boost for sequencing often ignored organisms | Amazing Science |

One of Germany’s states has provided a big boost for biologists who want to decipher the genomes of organisms that don’t get much attention. This week, the state of Hessen, which includes Frankfurt, awarded its local institutions €17.6 million, the first half of a 7-year grant for sequencing plants, animals, and fungi. The award includes funding for the high-quality sequencing of about 700 organisms, and for the partial sequencing or resequencing of thousands more.


“German scientists are going to take a big step forward in understanding the genomic basis of life,” says W. John Kress, a researcher at the Smithsonian Institution in Washington, D.C., who helped conceive the Earth BioGenome Project, an ambitious effort to sequence much of life on Earth.


The grant will create the new LOEWE-Zentrum für Translationale Biodiversitätsgenomik (LOEWE-TBG)—loosely translated as the Translational Biodiversity Genomics Excellence Center. It is the brainchild of Axel Janke, Markus Pfenninger, and Steffen Pauls, genomics researchers at the Senckenberg Research Institute and Natural History Museum in Frankfurt. The center, scheduled to open in January 2018, will involve the museum, Goethe University Frankfurt, the Justus Liebig University Giessen, and the Fraunhofer Institute for Molecular Biology and Applied Ecology.  

Via Integrated DNA Technologies
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Mice Provide Insight Into Genetics of Autism Spectrum Disorders

Mice Provide Insight Into Genetics of Autism Spectrum Disorders | Amazing Science |

While the definitive causes remain unclear, several genetic and environmental factors increase the likelihood of autism spectrum disorder, or ASD, a group of conditions covering a “spectrum” of symptoms, skills and levels of disability.


Taking advantage of advances in genetic technologies, researchers led by Alex Nord, assistant professor of neurobiology, physiology and behavior with the Center for Neuroscience at the University of California, Davis, are gaining a better understanding of the role played by a specific gene involved in autism. The collaborative work appears June 26 in the journalNature Neuroscience.


“For years, the targets of drug discovery and treatment have been based on an unknown black box of what’s happening in the brain,” said Nord. “Now, using genetic approaches to study the impact of specific mutations found in cases, we’re trying to build a cohesive model that links genetic control of brain development with behavior and brain function.”


The Nord laboratory studies how the genome encodes brain development and function, with a particular interest in understanding the genetic basis of neurological disorders.


There is no known specific genetic cause for most cases of autism, but many different genes have been linked to the disorder. In rare, specific cases of people with ASD, one copy of a gene called CHD8 is mutated and loses function. The CHD8 gene encodes a protein responsible for packaging DNA in cells throughout the body. Packaging of DNA controls how genes are turned on and off in cells during development. 


Because mice and humans share on average 85 percent of similarly coded genes, mice can be used as a model to study how genetic mutations impact brain development. Changes in mouse DNA mimic changes in human DNA and vice-versa. In addition, mice exhibit behaviors that can be used as models for exploring human behavior.

Via Mariaschnee
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Better single-cell whole-genome analysis by Linear Amplification via Transposon Insertion (LIANTI)

Better single-cell whole-genome analysis by Linear Amplification via Transposon Insertion (LIANTI) | Amazing Science |

Genomic changes in individual cells can eventually lead to cancer or other diseases. So scientists would like to be able to sequence the genome in a single cell. But the methods to do so can be plagued by the preferential amplification of some regions of the genome over others, leading to incomplete sequence coverage.


A team led by X. Sunney Xie of Harvard University and Peking University has developed a whole-genome amplification method that reduces such bias and errors (Science 2017, DOI: 10.1126/science.aak9787). In the method, called LIANTI, researchers fragment genomic DNA from a single cell by inserting pieces of DNA called transposons. The transposons tag the DNA fragments so that they get amplified linearly instead of exponentially. The amplified DNA is then used to generate a library for subsequent DNA sequencing.


Compared with other whole-genome amplification methods, LIANTI has more uniform amplification and higher sequence coverage. The method enabled the detection of a type of mutation called copy-number variation, which involves the gain or loss of regions of the genome, which is hard to detect with high resolution using other amplification methods. The researchers were even able to characterize so-called micro-copy-number variations, which are smaller than 100,000 bases, with a resolution of about 10,000 bases.


Xie and coworkers used this ability to detect gains and losses of sequences to show that initiation of DNA replication is random and differs from cell to cell. They also showed that many single-nucleotide variations detected in previous single-cell sequencing are artifacts caused by instability of the DNA bases.

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The Earth BioGenome Project Aims to Sequence **All** Eukaryotic Species

The Earth BioGenome Project Aims to Sequence **All** Eukaryotic Species | Amazing Science |

An unfunded project with an ambitious goal promises to shed light on the evolutionary history of higher organisms and enhance conservation efforts. But is the $4.8 billion project well-conceived?


Since the Human Genome Project was completed in 2003, large-scale genome sequencing efforts have proliferated. For example, Genome 10K was launched in 2009 to sequence the genomes of at least one individual from each vertebrate genus, approximately 10,000 genomes. Two years later, the i5K was unveiled as an initiative to sequence the genomes of 5000 arthropod species. 2015 saw the announcement of the B10K Project, which plans to generate representative draft genome sequences from all extant bird species within five years. The list goes on and on and on.


But a recently announced project has a more ambitious goal: to sequence all eukaryotic species on Earth. On February 23rd, the Earth BioGenome Project was officially announced at BioGenomics2017, the Global Biodiversity Genomics Conference held at the Smithsonian National Museum of Natural History in Washington, D.C. As reported in Science the next day, the first step of the project would be to sequence in great detail the DNA of a member of each eukaryotic family (about 9,000 in all) to create reference genomes on par or better than the reference human genome. Next would come sequencing to a lesser degree, a species from each of the 150,000 to 200,000 genera. Finally, the participants obtain rough genomes of the 1.5 million remaining known eukaryotic species.


“I think the project is a good idea and will make an important contribution,” said Luke Thompson, a research associate at the National Oceanic and Atmospheric Administration and manager of the Earth Microbiome Project, which was founded in 2010 as a massively collaborative effort to characterize microbial life on this planet. “Numerous insights on the history and evolution of life on Earth are sure to follow from this work.”


According to Thompson, the first stage of the project in particular would be very valuable. “This would provide immediate insight to the evolutionary history of higher organisms, improve taxonomic classification, and provide genomic templates for sequencing individual genera and species,” he said. “Speaking from a microbial perspective, which is my area of expertise, such an effort will provide a foundation for studies of co-evolution and symbiosis between microorganisms and higher organisms, including insights into the endosymbiosis events which enabled the fantastic radiation of eukaryotic diversity.”


The 10-year project, which is currently unfunded, would cost an estimated $4 to $5 billion to complete. As such, some scientists have argued that it would not be a wise use of money and might take away funds from research endeavors focused on other important goals such as improving human health. “The number one challenge is getting buy-in from the scientific community,” said John Kress, a research botanist and curator at the Smithsonian National Museum of Natural History and co-organizer of the Earth BioGenome Project. “This effort will enhance what they do as biologists and conservationists and technologists and will not take funding away from their major projects, but actually add funding to what they want to do.”


In addition, Kress will have to work with project co-organizers Harris Lewin, an expert in mammalian comparative and functional genomics at the University of California, Davis, and Gene Robinson, an evolutionary biologist at the University of Illinois at Urbana-Champaign, to tackle the second biggest challenge: acquiring the funding to get the project off the ground. “Along with that is convincing other funding agencies and research agencies that this thing has legs and this will help float a lot of boats,” Kress said.


If the project is funded, the co-organizers will have to overcome many more hurdles. Although they would leave the bulk of the analysis to other scientists using the open-access data, the trio plans to collaborate with other genome sequencing projects to develop standardized analytic tools and standards to ensure high-quality genome sequences. “We can only be successful if it is a community effort,” Kress said.


Even with the help of others, organizing a project of this scope would be very challenging. Managing the metadata in particular would be critical, Thompson said. “For each species, we will need to have photographs or micrographs, common and scientific names, body measurements, location and date of collection, and as many other parameters as possible,” he said. “These metadata are critical to interpreting the genome sequences.”

Via Integrated DNA Technologies
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Octopuses can basically edit their genes on the fly

Octopuses can basically edit their genes on the fly | Amazing Science |

You're a complex organism. You socialize with family and friends, you solve puzzles and make choices. Humans may be some of the most cerebral animals on the planet, but we know we're not alone in having this sort of behavioral complexity. Crows use tools. Primates create incredible social structures. Whales congregate.


But all of these critters have one thing in common: they're vertebrates. Members of our subphylum share more than just a backbone; our common ancestor gifted us with the sort of structure and central nervous system that lends itself to behavioral complexity.


And then there are cephalopods. They can solve a shocking number of complex puzzles, suggesting a cognition that rivals those found in the vertebrate world—even though they last shared a common ancestor with us at least 500 million years ago. In the world of invertebrates, octopuses, squid, and cuttlefish stand apart.


We may finally have some idea why. According to a study published in Cell, these creatures have an uncanny ability to manipulate the instructions found within their DNA. An unprecedented panache for RNA editing may explain why cephalopods are so bright and adaptable.

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DNA sequencing gives clues to why woolly mammoth died out

DNA sequencing gives clues to why woolly mammoth died out | Amazing Science |

The last woolly mammoths to walk the Earth were so wracked with genetic disease that they lost their sense of smell, shunned company, and had a strange shiny coat. That's the verdict of scientists who have analyzed ancient DNA of the extinct animals for mutations. The studies suggest the last mammoths died out after their DNA became riddled with errors. The knowledge could inform conservation efforts for living animals.


There are fewer than 100 Asiatic cheetahs left in the wild, while the remaining mountain gorilla population is estimated at about 300. The numbers are similar to those of the last woolly mammoths living on Wrangel Island in the Arctic Ocean around 4,000 years ago.


Dr Rebekah Rogers of the University of California, Berkeley, who led the research, said the mammoths' genomes "were falling apart right before they went extinct". This, she said, was the first case of "genomic meltdown" we have seen in a single species.


Woolly mammoths were once common in North America and Siberia. They were driven to extinction by environmental factors and possibly human hunting about 10,000 years ago. Small island populations clung on until about 4,000 years ago. "There was this huge excess of what looked like bad mutations in the genome of the mammoth from this island," said Dr Rogers. "We found these bad mutations were accumulating in the mammoth genome right before they went extinct."


Knowledge of the last days of the mammoth could help modern species on the brink of extinction, such as the panda, mountain gorilla and Indian elephant. The lesson from the woolly mammoth is that once numbers drop below a certain level, the population's genetic health may be beyond saving. Genetic testing could be one way to assess whether levels of genetic diversity in a species are enough to give it a chance of survival. A better option is to stop numbers falling too low.


"When you have these small populations for an extended period of time they can go into genomic meltdown, just like what we saw in the mammoth," said Dr Rogers.


"So if you can prevent these organisms ever being threatened or endangered then that will do a lot more to help prevent this type of genomic meltdown compared to if you have a small population and then bring it back up to larger numbers because it will still bear those signatures of this genomic meltdown."

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Making single-cell RNA sequencing widely available

Making single-cell RNA sequencing widely available | Amazing Science |

Sequencing messenger RNA molecules from individual cells offers a glimpse into the lives of those cells, revealing what they’re doing at a particular time. However, the equipment required to do this kind of analysis is cumbersome and not widely available.


MIT researchers have now developed a portable technology that can rapidly prepare the RNA of many cells for sequencing simultaneously, which they believe will enable more widespread use of this approach. The new technology, known as Seq-Well, could allow scientists to more easily identify different cell types found in tissue samples, helping them to study how immune cells fight infection and how cancer cells respond to treatment, among other applications.


“Rather than trying to pick one marker that defines a cell type, using single-cell RNA sequencing we can go in and look at everything a cell is expressing at a given moment. By finding common patterns across cells, we can figure out who those cells are,” says Alex K. Shalek, the Hermann L.F. von Helmholtz Career Development Assistant Professor of Health Sciences and Technology, an assistant professor of chemistry, and a member of MIT’s Institute for Medical Engineering and Science.


Shalek and his colleagues have spent the past several years developing single-cell RNA sequencing strategies. In the new study, he teamed up with J. Christopher Love, an associate professor of chemical engineering at MIT’s Koch Institute for Integrative Cancer Research, to create a new version of the technology that can rapidly analyze large numbers of cells, with very simple equipment.


“We’ve combined his technologies with some of ours in a way that makes it really accessible for researchers who want to do this type of sequencing on a range of different clinical samples and settings,” Love says. “It overcomes some of the barriers that are facing the adoption of these techniques more broadly.”


Love and Shalek are the senior authors of a paper describing the new technique in the Feb. 13 issue of Nature Methods. The paper’s lead authors are Research Associate Todd Gierahn and graduate students Marc H. Wadsworth II and Travis K. Hughes.

Via Integrated DNA Technologies
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NovaSeq: Illumina wants to sequence your whole genome for just $100

NovaSeq: Illumina wants to sequence your whole genome for just $100 | Amazing Science |

The first sequencing of the whole human genome in 2003 cost roughly $2.7 billion, but DNA sequencing giant Illumina has now unveiled a new machine that the company says is “expected one day” to order up your whole genome for less than $100.


Illumina’s CEO Francis deSouza showed off the machine, called the NovaSeq, onstage at the JP Morgan Healthcare Conference in downtown San Francisco today, telling the crowd the machine’s scanning speed could decipher an entire human genome in less than an hour.


Let that sink in for a moment. In less than 15 years we went from what once took billions of dollars and over a decade of research to an hour’s worth of time with the promise of a blip of the cost. But the price for genome sequencing has been in continuous free fall since the beginning. In 2006, Illumina’s first machine could sequence a human genome for $300,000, and in 2014 the company announced it could do the same thing for $1,000.


The rapid reduction in costs have already helped in clinical research, but even greater speed and a lowered price point will likely be enticing to health startups with a focus on the consumer. While plenty of clinics and researchers have been able to access genetic data in cancer research and other diseases, consumer interest in genetic research has also piqued thanks to tests from startups such as 23andMe and AncestryDNA. And celebrities such as Angelina Jolie have helped spur interest in women to get genomic screenings for breast cancer, such as BRCA-1 and BRCA-2, like Color Genomics provides.


The San Diego-based Illumina plays a huge back-end role in many of these direct-to-consumer tests. If you’ve ever had your DNA sequenced (or genotyped as is the case for those using 23andMe) it’s highly likely it was done on one of Illumina’s machines.


Many of these testing services already cost a couple hundred dollars and the lowered cost and higher speed could not only give them a larger margin in profits but the ability to process faster and possibly bring in a higher load of customers. Illumina’s new machine is meant to be a lower-priced device and comes in two models — NovaSeq 5000 for $850,000 and the NovaSeq 6000 for $985,000.


Six customers have already come on board to test NovaSeq, including the Chan Zuckerberg Biohub (the life sciences arm started by Mark Zuckerberg and his wife Priscilla Chan), the Broad Institute of MIT and Harvard and biotech companies Regeneron and Human Longevity Inc. DeSouza also confirmed each company had put in a purchase order for the new machine.


But Illumina doesn’t have its device down to $100 a pop just yet. And it will still take some time to interpret the data. Of course, the rapid adoption of AI may help speed things up a bit there, and the mind-boggling reduction in price to get this genetic information is exciting.

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Study unmasks the genetic complexity of cancer cells within the same tumor

Study unmasks the genetic complexity of cancer cells within the same tumor | Amazing Science |

A new study led by Cedars-Sinai investigators dramatically illustrates the complexity of cancer by identifying more than 2,000 genetic mutations in tissue samples of esophageal tumors. The findings reveal that even different areas of individual tumors have various genetic patterns.


The study results, published in the journal Nature Genetics, help explain why it is so difficult to battle cancer by targeting a specific genetic defect. A surgeon who performs a single biopsy on a patient’s tumor can decode only part of the tumor and its genetic variations. Additionally, cancer cells constantly change their makeup.


“A tumor is not a single disease,” said Dechen Lin, PhD, assistant professor and research scientist in the Division of Hematology and Oncology in the Cedars-Sinai Department of Medicine. “It’s many diseases within the same person and over time. There are millions of cells in a tumor, and a significant proportion of them are different from each other.” Lin was the project coordinator for the multicenter study.


The cancer that the team studied, esophageal squamous cell carcinoma, is especially difficult to treat. The disease attacks the esophagus, the hollow tube that connects the throat to the stomach. The five-year survival rate for patients with esophageal cancer is about 20 percent, according to the American Cancer Society.


To create their catalog of mutations, the study’s investigators called on high-powered computers to compile genetic data on 51 tumor samples taken from 13 patients. Through complex algorithms, they analyzed both the genes and the processes, known as epigenetics, that turned the genes’ activities on and off within the cancer cells.


Using these techniques, the investigators identified 2,178 genetic variations in the sampled tumors. Dozens of the variations involved genes known to be associated with enabling the development of cancer. The most striking finding was that many important mutations were detected only in some areas of a tumor, highlighting the complexity of the cancer cells. This finding also demonstrated the potential for inaccurate interpretation of a cancer’s genetic makeup using the single-biopsy method, which is the standard approach in the clinic.


Using these techniques, the investigators identified 2,178 genetic variations in the sampled tumors. Dozens of the variations involved genes known to be associated with enabling the development of cancer. The most striking finding was that many important mutations were detected only in some areas of a tumor, highlighting the complexity of the cancer cells. This finding also demonstrated the potential for inaccurate interpretation of a cancer’s genetic makeup using the single-biopsy method, which is the standard approach in the clinic.

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All 2.3 Million Species Are Mapped into a Single Circle of Life

All 2.3 Million Species Are Mapped into a Single Circle of Life | Amazing Science |

Lineages of all known species on earth are finally pieced together.


Since Charles Darwin's day, biologists have depicted how new organisms evolve from old ones by adding branches to numerous trees that represent portions of the animal, plant and microbial kingdoms. Researchers from a dozen institutions recently completed a three-year effort to combine tens of thousands of trees into one diagram, most readable as a circle (above). The lines inside the circle represent all 2.3 million species that have been named. Biologists have genetic sequences for only about 5 percent of them, however; as more are finished, the relationships within and across groups of species may change. Experts estimate that up to 8.7 million species may inhabit the planet (about 15,000 are discovered every year). “We expect the circle to broaden,” says Karen Cranston, a computational evolutionary biologist at Duke University.


Anyone can propose updates to the database ( Greater detail could improve understanding of evolution and help scientists invent drugs, make crops more productive and better control infectious diseases.

Via Neelima Sinha
Boris Limpopo's curator insight, December 31, 2016 6:20 AM
Oltre 2 milioni di specie nel circolo della vita
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Thousands of new microbial communities identified in human body

Thousands of new microbial communities identified in human body | Amazing Science |

A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, yielding new insights into the role these microbes play in human health.


The study, from researchers at Harvard T.H. Chan School of Public Health, Broad Institute of MIT and Harvard, and University of Maryland School of Medicine, presents a three-fold expansion of data from the National Institutes of Health Human Microbiome Project, providing unprecedented depth and detail about human microbial diversity. The new information allows researchers to identify differences that are unique to an individual's microbes—just like some human genome variants are unique to each individual—and track them across the body and over time.

The study will be published online September 20, 2017 in Nature.


"This study has given us the most detailed information to date about exactly which microbes and molecular processes help to maintain health in the human microbiome," said Curtis Huttenhower, associate professor of computational biology and bioinformatics at Harvard Chan School, associate member of the Broad Institute, and senior author of the study.


The researchers analyzed 1,631 new samples from 265 individuals, from diverse body sites and at multiple points in time. The scientists used DNA sequencing tools that allowed them to precisely identify which organisms are present in various body sites, as well as what they might be able to do. Examining microbes at multiple time points further allowed them to determine which parts of the community might change slowly, rapidly, or stay relatively stable over time.


The findings:

  • Provide one of the largest profiles of non-bacterial members—viruses and fungi—of the microbiome across the body
  • Identified microbes with specific strains within each body site
  • Profile the biochemical activity that allows microbes to help maintain human health
  • Identify how the microbes and their biochemistry change over time


Huttenhower said the new study also emphasizes how much scientists still don't know about the makeup and function of the human microbiome. Learning more about it will take time, he said.

"Just as sequencing one human genome, without information about variability or context, didn't immediately lead to extensive new drugs or therapies, so too will we need to look at the microbiome with an extremely fine lens, in many different contexts, so that we can understand and act on its specific, personalized changes in any individual disease or condition," said Jason Lloyd-Price, postdoctoral associate at the Broad Institute, postdoctoral fellow at Harvard Chan School, and lead author of the study. He added that the study also provides a large data resource to the scientific community that will help drive future research, discoveries, and the development of new methods in studying the human microbiome.

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Genomic Data Growing Faster Than Twitter, YouTube and Astronomy

Genomic Data Growing Faster Than Twitter, YouTube and Astronomy | Amazing Science |

In the age of Big Data, it turns out that the largest, fastest growing data source lies within your cells. Quantitative biologists at the University of Illinois Urbana-Champaign and Cold Spring Harbor Laboratory, in New York, found that genomics reigns as champion over three of the biggest data domains around: astronomy, Twitter, and YouTube.


The scientists determined which would expand the fastest by evaluating acquisition, storage, distribution, and analysis of each set of data. Genomes are quantified by their chemical constructs, or base pairs. Genomics trumps other data generators because the genome sequencing rate doubles every seven months. If it maintains this rate, by 2020 more than one billion billion bases will be sequenced and stored per year, or 1 exabase. By 2025, researchers estimate the rate will be almost one zettabase, one trillion billion bases, per sequence per year. “What does it mean to have more genomes than people on the planet?”—Michael Schatz, Cold Spring Harbor Laboratory


90 percent of the genome data analyzed in the study was human. The scientists estimate that 100 million to 2 billion human genomes will be sequenced by 2025. That’s a four to five order of magnitude of growth in ten years, which far exceeds the other three data generators they studied. “For human genomics, which is the biggest driver of the whole field, the hope is that by sequencing many, many individuals, that knowledge will be obtained to help predict and cure a variety of diseases,” says University of Illinois Urbana-Champaign co-author, Gene Robinson. Before it can be useful for medicine, genomes must be coupled with other genomic data sets, including tissue information.


One reason the rate is doubling so quickly is because scientists have begun sequencing individual cells. Single-cell genome sequencing technology for cancer research can reveal mutated sequences and aid in diagnosis. Patients may have multiple single cells sequenced, and there could end up being more than 7 billion genomes sequenced.


That “is more than the population of the Earth,” says Michael Schatz, associate professor at Cold Spring Harbor Laboratory, in New York. “What does it mean to have more genomes than people on the planet?” What it means is a mountain of information must be collected, filed, and analyzed.


“Other disciplines have been really successful at these scales, like YouTube,” says Schatz. Today, YouTube users upload 300 hours of video every minute, and the researchers expect that rate to grow up to 1,700 hours per minute, or 2 exabytes of video data per year, by 2025. Google set up a seamless data-flowing infrastructure for YouTube. They provided really fast Internet, huge hard drive space, algorithms that optimized results, and a team of experienced researchers.

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Plant scientists plan massive effort to sequence 10,000 genomes

Plant scientists plan massive effort to sequence 10,000 genomes | Amazing Science |

Hopes of sequencing the DNA of every living thing on earth are taking a step forward with the announcement of plans to sequence at least 10,000 genomes representing every major clade of plants and eukaryotic microbes. Chinese sequencing giant BGI and the China National Genebank (CNGB) held a workshop yesterday on the sidelines of the International Botanical Congress, being held this week in BGI's hometown of Shenzhen, to discuss what they are calling the 10KP plan. About 250 plant scientists participated in the discussions and "are raring to go," says Gane Ka-Shu Wong, a genomicist and bioinformaticist at University of Alberta in Edmonton.


The 10KP plan will be a key part of the Earth BioGenome Project (EBP), an ambitious and still evolving scheme to get at least rough sequence data on the 1.5 million eukaryotic species, starting with detailed sequences of one member of each of the 9000 eukaryotic families. The effort to sequence plants is moving ahead a bit faster than other aspects of EBP "because plant scientists are more collaborative," Wong says jokingly.


The 10KP plan is also building on a previous 1000 plant (1KP) transcriptome project. That effort, launched in 2012 and now nearing completion, was also led by BGI, where Wong is an associate director. 

Via Integrated DNA Technologies
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In a Lost Baby Tooth, Scientists Find Ancient Denisovan DNA

In a Lost Baby Tooth, Scientists Find Ancient Denisovan DNA | Amazing Science |

More than 100,000 years ago in a Siberian cave there lived a child with a loose tooth. One day her molar fell out, and fossilized over many millenniums, keeping it safe from the elements and the tooth fairy.


But she wasn’t just any child. Scientists say she belonged to a species of extinct cousins of Neanderthals and modern humans known today as the Denisovans. And in a paper published Friday in the journal Science Advances, a team of paleoanthropologists reported that she is only the fourth individual of this species ever discovered.


“We only have relatively little data from this archaic group, so having any additional individuals is something we’re very excited about,” saidViviane Slon, a doctoral candidate at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and lead author of the study.


The scant fossil record for these ancient hominins previously included only two adult molars and a finger bone. The Denisovans were only correctly identified in 2010 by a team of researchers led by Svante Paabo, who used the finger bone to sequence the species’ genome.

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Dog family tree reveals hidden history of canine diversity created by humans

Dog family tree reveals hidden history of canine diversity created by humans | Amazing Science |
Genetic map showing how dog breeds are related provides a wealth of information about their origins.


What a tangled web humans have weaved for domestic dog breeds. A new family tree of dogs containing more than 160 breeds reveals the hidden history of man’s best friend, and even hints how studying canine genomes might help with research into human disease.


In a study published on 25 April 2017 in Cell Reports, scientists examined the genomes of 1,346 dogs to create one of the most diverse maps produced so far tracing the relationship between breeds1. The map shows the types of dog that people crossed to create modern breeds and reveals that canines bred to perform similar functions, such as working and herding dogs, don't necessarily share the same origins. The analysis even hints at an ancient type of dog that could have come over to the Americas with people thousands of years before Christopher Columbus arrived in the New World.


The new work could come as a surprise to owners and breeders who are familiar with how dogs are grouped into categories. “You would think that all working dogs or all herding dogs are related, but that isn’t the case,” says Heidi Parker, a biologist at the US National Institutes of Health (NIH) in Bethesda, Maryland, and a study author.


When geneticists tried to map out herding-dog lineages in the past, they couldn’t do so accurately. Parker and Elaine Ostrander, also a biologist at the NIH and a study author, say that this was because herding dogs emerged through selective breeding at multiple times and in many different places. “In retrospect, that makes sense,” says Ostrander. “What qualities you’d want in a dog that herds bison are different from mountain goats, which are different from sheep, and so on.”


Most of the breeds in the study arose from dog groups that originated in Europe and Asia. But domestic dogs came to the Americas thousands of years ago, when people crossed the Bering land bridge linking Alaska and Siberia. These New World dogs later disappeared when European and Asian dogs arrived in the Americas. Researchers have looked for the genetic legacy of these ancient canines in the DNA of modern American breeds, but have found little evidence until now.


The way that two South American breeds, the Peruvian hairless dog and the Xoloitzcuintli, clustered together on the family tree suggested to Ostrander and Parker that those animals could share genes not found in any of the other breeds in their analysis. Parker thinks that those genes could have come from dogs that were present in the Americas before Columbus’s arrival. “I think our view of the formation of modern dog breeds has historically been one-dimensional,” says Bob Wayne, an evolutionary biologist at the University of California, Los Angeles. “We didn’t consider that the process has a deep historical legacy.”


That extends to what was probably the first period of domestication for canines in hunter-gatherer times. Ostrander and Parker think that dog breeds underwent two major periods of diversification. Thousands of years ago, dogs were selected for their skills, whereas a few hundred years ago, the animals were bred for physical traits. “You would never be able to find something like this with cows or cats,” says Wayne, “We haven’t done this kind of intense deliberate breeding with anything but dogs.”

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A geographically-diverse collection of 418 human gut microbiome pathway genome databases

A geographically-diverse collection of 418 human gut microbiome pathway genome databases | Amazing Science |

Advances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available.


However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, scientists developed GUTCYC, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using METAPATHWAYS, enabling reproducible functional metagenomic annotation. They also generated metabolic network reconstructions for each metagenome using the PATHWAYTOOLS software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GUTCYC provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GUTCYC data products are searchable online, or may be downloaded and explored locally using METAPATHWAYS and PATHWAY TOOLS.

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Young poo: Gut microbes of young killifish can extend the lifespans of older fish

Young poo: Gut microbes of young killifish can extend the lifespans of older fish | Amazing Science |

The gut microbes of young killifish can extend the lifespans of older fish – hinting at the microbiome’s role in aging.


It may not be the most appetizing way to extend life, but researchers have shown for the first time that older fish live longer after they consumed microbes from the poo of younger fish. The findings were posted to the preprint server on 27 March1 by Dario Valenzano, a geneticist at the Max Planck Institute for Biology of Ageing in Köln, Germany, and his colleagues.


So-called ‘young blood’ experiments that join the circulatory systems of two rats — one young and the other old — have found that factors coursing through the veins of young rodents can improve the health and longevity of older animals. But the new first-of-its-kind study examined the effects of 'transplanting' gut microbiomes on longevity.


“The paper is quite stunning. It’s very well done,” says Heinrich Jasper, a developmental biologist and geneticist at the Buck Institute for Research on Aging in Novato, California, who anticipates that scientists will test whether such microbiome transplants can extend lifespan in other animals.


Life is fleeting for killifish, one of the shortest-lived vertebrates on Earth: the fish hits sexual maturity at three weeks old and dies within a few months. The turquoise killifish (Nothobranchius furzeri) that Valenzano and his colleagues studied in the lab inhabits ephemeral ponds that form during rainy seasons in Mozambique and Zimbabwe.


Previous studies have hinted at a link between the microbiome and aging in a range of animals. As they age, humans2 and mice3 tend to lose some of the diversity in their microbiomes, developing a more uniform community of gut microbes, with once-rare and pathogenic species rising to dominance in older individuals4. The same pattern holds true in killifish, whose gut microbiomes at a young age are nearly as diverse as those of mice and humans, says Valenzano. “You can really tell whether a fish is young or old based on its gut microbiota.”


To test whether the changes in the microbiome had a role in ageing, Valenzano’s team ‘transplanted’ the gut microbes from 6-week-old killifish into middle-aged 9.5-week-old fish. They first treated the middle-aged fish with antibiotics to clear out their gut flora, then placed them in a sterile aquarium containing the gut contents of young fish for 12 hours. Killifish don’t usually eat faeces, Valenzano notes, but they would probe and bite at the gut contents to see whether it was food, ingesting microbes in the process. The transplanted microbes successfully recolonized the guts of the fish that received them, the team found. At 16 weeks of age, the gut microbiomes of middle-aged fish that received 'young microbes' still resembled those of 6-week-old fish.  


The young microbiome ‘transplant’ also had dramatic effects on the longevity of fish that got them: their median lifespans were 41% longer than fish exposed to microbes from middle-aged animals, and 37% longer than fish that received no treatment (antibiotics alone also lengthened lifespan, but to a lesser extent).

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Visualising the genome: Researchers create first 3D structures of active DNA

Visualising the genome: Researchers create first 3D structures of active DNA | Amazing Science |

Scientists have determined the first 3D structures of intact mammalian genomes from individual cells, showing how the DNA from all the chromosomes intricately folds to fit together inside the cell nuclei.


Researchers from the University of Cambridge and the MRC Laboratory of Molecular Biology used a combination of imaging and up to 100,000 measurements of where different parts of the DNA are close to each other to examine the genome in a mouse embryonic stem cell. Stem cells are 'master cells', which can develop -- or 'differentiate' -- into almost any type of cell within the body.


Most people are familiar with the well-known 'X' shape of chromosomes, but in fact chromosomes only take on this shape when the cell divides. Using their new approach, the researchers have now been able to determine the structures of active chromosomes inside the cell, and how they interact with each other to form an intact genome. This is important because knowledge of the way DNA folds inside the cell allows scientists to study how specific genes, and the DNA regions that control them, interact with each other. The genome's structure controls when and how strongly genes -- particular regions of the DNA -- are switched 'on' or 'off'. This plays a critical role in the development of organisms and also, when it goes awry, in disease.


The researchers have illustrated the structure in accompanying videos, which show the intact genome from one particular mouse embryonic stem cell. In the film, above, each of the cell's 20 chromosomes is colored differently.


In a second video regions of the chromosomes where genes are active are colored blue, and the regions that interact with the nuclear lamina (a dense fibrillar network inside the nucleus) are colored yellow. The structure shows that the genome is arranged such that the most active genetic regions are on the interior and separated in space from the less active regions that associate with the nuclear lamina. The consistent segregation of these regions, in the same way in every cell, suggests that these processes could drive chromosome and genome folding and thus regulate important cellular events such as DNA replication and cell division.


Professor Ernest Laue, whose group at Cambridge's Department of Biochemistry developed the approach, commented: "Knowing where all the genes and control elements are at a given moment will help us understand the molecular mechanisms that control and maintain their expression.


"In the future, we'll be able to study how this changes as stem cells differentiate and how decisions are made in individual developing stem cells. Until now, we've only been able to look at groups, or 'populations', of these cells and so have been unable to see individual differences, at least from the outside. Currently, these mechanisms are poorly understood and understanding them may be key to realizing the potential of stem cells in medicine."

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Scientists Announce HGP-Write, Project to Synthesize the Full Human Genome

Scientists Announce HGP-Write, Project to Synthesize the Full Human Genome | Amazing Science |

Proposals for a large public–private initiative to synthesize an entire human genome from scratch — an effort that could take a decade and require billions of dollars in technological development — were formally unveiled on 2 June 2016, almost a month after they were first aired at a secretive meeting.


Proponents of the effort, named ‘Human Genome Project—Write’ (HGP-write), write in Science that US$100 million from a range of funding sources would help to get their vision off the ground1. The team is led by synthetic biologist Jef Boeke at New York University; genome scientist George Church at Harvard Medical School in Boston, Massachusetts; and Andrew Hessel, a futurist at the commercial design studio Autodesk Research in San Rafael, California. But the idea — which essentially aims to develop technologies that reduce the cost of DNA synthesis — has not met with universal excitement among researchers.


To some, the proposal to create a human genome is praiseworthy for its ambition and sheer chutzpah: at present, only tiny bacterial genomes and a portion of a yeast genome have been made from scratch. But other researchers feel that HGP-write represents a needless centralization of work that is already taking place in companies trying to lower the price of synthesizing strings of DNA. Some of HGP-write’s proponents have financial stakes in those firms, which include Gen9 in Cambridge, Massachusetts. “My first thought was ‘so what’,” says Martin Fussenegger, a synthetic biologist at the Swiss Federal Institute of Technology in Zurich. “I personally think this will happen naturally. It’s just a matter of price at the end.”


Others think that the project should be delayed until its leaders can win broader support for the idea. In an e-mail sent to reporters, synthetic biologist Drew Endy, at Stanford University in California, and religion scholar Laurie Zoloth, at Northwestern University in Evanston, Illinois, say that the HGP-write team has not properly justified its aims, and that the project should be abandoned. “We are still waiting for a serious public debate with participation from a broad range of people,” they say.


Endy and Zoloth had already questioned the scientific rationale for synthesizing a human genome in May, when HGP-write was first aired at an invitation-only meeting at Harvard University that was attended by more than 100 scientists, entrepreneurs, lawyers and ethicists. The closed nature of the meeting also attracted criticism: Church told the health and medicine news service Stat that this was because the paper describing the effort was under embargo.


“There was a lot of confusion on the day about what was going on,” says Tom Ellis, a synthetic biologist at Imperial College London, who attended the meeting. “Some people were in the know on the [paper’s] review process and others were trying to find out.”


The three-page announcement of HGP-write fills in some detail. It notes that current technologies are both too expensive and too primitive to synthesize the 3-billion-base-pair human genome. The team calls for a series of pilot projects, including synthesizing much shorter segments of the genome and making slimmed-down chromosomes to do specific tasks, to make its eventual goal doable. The whole project should require less than $3 billion (the price of the publicly funded Human Genome Project), the researchers say.


“I think it’s a brilliant project,” says Paul Freemont, a structural biologist at Imperial College London, who attended the meeting. “If you want to do this, it’s going to be on the same scale as the Human Genome Project, it’s going to need some big funding agencies and hundreds and hundreds of researchers around the world.”


Read more in Nature



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Inside the Goth Chicken: Black Bones, Black Meat, and a Black Heart 

Inside the Goth Chicken: Black Bones, Black Meat, and a Black Heart  | Amazing Science |

In the historical novel The Black Tulip, written by Alexandre Dumas, an honest and decent Dutch tulip fancier is nearly brought to ruin by his quest to breed a purely black flower. More precisely, his misadventure is due to the dastardly schemes of his neighbor, who, frantic with spite and jealousy over the plants, frames him for a political crime and gets him thrown in jail. The potboiler plot is ridiculously overheated, but Dumas got one thing exactly right: People will go nuts over the desire to possess a living thing in a strange and beautiful color.


The breed was developed in Indonesia, but due to concerns over avian flu, the U.S. Department of Agriculture bans direct imports from that nation. So these extraordinary chickens are very hard to get in America and, as a result, are extremely expensive. The best-known and most reputable breeder, Greenfire Farms, offers them for more than a thousand dollars per pair of juveniles; just one day-old chick of unknown sex goes for $199, plus shipping and handling.  You can find Cemanis advertised for cheaper, but the discussion forums of (for example) suggest that you risk getting scammed. Order eggs off eBay and you might find yourself hatching out counterfeit chicks of silver or brown.


Cemanis are not the only black birds, but most of the others have pink tongues and deep brown eyes, along with innards of the normal hues. A few wild birds are naturally melanistic, meaning that due to genetic variations they have more pigment production in their feathers or skin. Their feathers are darker than usual, often brown or sooty grey. (See Nautilus’ story on the wide range of birds with abnormal colors.)


This phenomenon of internal blackness, which is called fibromelanosis, seems to occur in only three other oddball breeds: the Swedish Bohuslän-Dals svarthöna, the Vietnamese Black H’Mong, and the Silkie, an ancient breed of fluffy, five-toed chickens with feathers that look like hair. In 2011, a team of Swedish, American, and Chinese researchers figured out the genetics of this strange phenomenon. It was lead by Leif Andersson, a Swedish geneticist at Uppsala University who has long been interested in the genetic origins of striking phenotypes in livestock. The team discovered that fibromelanosis in all three breeds is caused by a mutation that affects how pigment-producing cells travel in the very early stages of development.


Normally, the precursor cells that will later give rise to melanin-producing melanocytes travel through the developing embryo in a specific pattern, winding up in the tissues that will develop into the skin and the eyes. In these birds, the cells also turn within, invading and colonizing tissues that will later turn into the fibers that hold the body together—the abdominal lining and the connective fibers and sheaths that encase the muscles and organs. There they continue to multiply instead of shutting down, resulting in significant deposits of dark color throughout the inside of the bird.


This genetic fluke is the result of two sizable chunks of DNA that are duplicated within the chromosome (one of them upside-down). Inside those stretches, Andersson’s group also pinpointed a gene called endothelian-3 (EDN3), known to be involved in the regulation of pigment-producing melanocyte cells. About 10 times as much EDN3 was expressed in the skin of adult black chickens than in other breeds. (The lovely black metallic sheen of the Cemani’s feathers actually has nothing to do with this variation; in fact, some Silkies have white feathers despite their black skin and black bones.)

Via Integrated DNA Technologies
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Scientists Discover a Way to Sequence DNA of Rare or Even Extinct Animals

Scientists Discover a Way to Sequence DNA of Rare or Even Extinct Animals | Amazing Science |

Rare and extinct animals are preserved in jars of alcohol in natural history museum collections around the world, which provide a wealth of information on the changing biodiversity of the planet. These preserved specimens of snakes, lizards, frogs, fish and other animals can last up to 500 years when processed in a chemical called formalin. While formalin helps preserve the specimen making it rigid and durable, it poses a challenge to extracting and sequencing DNA. Furthermore, DNA degrades and splits into small fragments over time. This fragmented DNA is difficult to amplify into long informative stretches of DNA that can be used to examine evolutionary relationships among species when using older DNA sequencing technology. Therefore, scientists have not been able to effectively sequence DNA from these specimens until now.

LSU Museum of Natural Science Curator and Professor Christopher Austin and his collaborator Rutgers-Newark Assistant Professor Sara Ruane developed a protocol and tested a method for DNA sequencing thousands of genes from these intractable snake specimens. Their research was published today in the international scientific journal Molecular Ecology Resources.

“Natural history museums are repositories for extinct species. Unfortunately, naturalists in the 1800s were not collecting specimens for analyses we conduct today such as DNA sequencing. Now with these new methods, we can get the DNA from these very old specimens and sequence extinct species like the Ivory Billed Woodpecker, the Tasmanian Wolf and the Dodo Bird,” Austin said.

He and Ruane found and tested an approach that includes taking a small piece of liver tissue from the snake specimen, heating it up over a longer period of time and applying an enzyme that digests the tissue sample and enables the DNA to be extracted. Their minimally invasive protocol preserves the specimen so additional information can be collected from the specimen in the future. It also includes applying the latest technology to chemically sequence the specimens’ DNA.

“A genome is a complex jigsaw puzzle broken up in to hundreds of millions of small pieces. We can sequence those pieces and computationally put them back together,” Austin said.

They extracted and sequenced the DNA of 13 historic or rare snake specimens from all over the world many of which had never been analyzed using modern genetic methods. Some of the specimens were more than 100 years old. They also integrated these data with modern samples to create a genetic family tree, or phylogeny, that maps the evolutionary relationships of various snake species. This work resulted in thousands of genetic markers for snake specimens collected as far back as the early 1900s.

“The exciting thing about this work is that it makes species that have been essentially lost to science, due to extirpation, rarity or general secretiveness, which applies to many animals and not just snakes, available for scientific research in the modern age of genomics,” Ruane said.

“We also believe this research will benefit scientists working with rare animals that are either hard to collect or extinct but are represented in fluid-preserved historical collections. It also underscores the continued importance of museum collections in modern science,” Austin said.

Via Integrated DNA Technologies
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Gut Microbes Influence Effectiveness of Dieting

Gut Microbes Influence Effectiveness of Dieting | Amazing Science |
Your microbiota may not be on your side as you try improving your diet this New Year's. In a new study, researchers explore why mice that switch from an unrestricted American diet to a healthy, calorie-restricted, plant-based diet don't have an immediate response to their new program. They found that certain human gut bacteria need to be lost for a diet plan to be successful.
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