Monthly Archives: March 2017

In just a few years, scientists will unveil a creature whose every letter of DNA was written by a human being. It will be a yeast cell with a fully designer genome, and biological capabilities seen nowhere else in nature.

Today, a global team of scientists has announced a major milestone in their decade-long quest to create a fully synthetic yeast genome. As described in the journal Science, the hundreds of scientists have completed work on six of the yeasts 16 chromosomes (the individual stands of DNA that make up a genome). Meanwhile, the remaining 10 chromosomes (plus one extra, not found in nature) have been designed and are awaiting production.

The synthetic yeast will be a huge advancement in bioengineering. It will be a proof of concept that scientists can design and implement genome-wide changes, tailoring microorganisms in major ways for further engineering and study. It means we may be able to create whole new species of microorganisms for industrial or scientific purposes.

No, this isnt playing God, the scientists behind the project say. In their view, rewriting the yeast genome is more like domestication. No one created a dog; they adapted a wolf, says Sarah Richardson, a synthetic biologist who is the lead author on one of the Science papers describing the project.

Right now, biologists have a lot of genetic engineering tools at their disposal. CRISPR/Cas9 allows biologists to neatly snip out one single gene and replace it with another. Recombinant DNA is how weve coaxed bacteria to create human insulin a treatment for diabetics. But those techniques are for tiny edits. This yeast project is a rewriting and reorganization of the whole genetic book.

The project, called Sc2.0 as in the 2.0 version of Saccharomyces cerevisiae, a.k.a. household yeast started 10 years ago. Now the end is in sight. In just a few more years, the researchers should be able to unite all 17 synthetic chromosomes in one cell.

Research efforts have developed synthetic bacteria genomes before. But yeast is vastly more complicated. The most commonly used bacteria in genetic engineering, Richardson explains, has about 4 million base pairs of DNA. (Base pairs you might remember from high school are the individual building blocks that make up DNA: adenine-thymine; cytosine-guanine. No shame if youve forgotten.) Yeast has around 12 million base pairs.

Building that all from scratch is an enormous task which is why the Science papers published today have hundreds of authors.

But why all the effort? This project has two main benefits.

1) It helps scientists understand the fundamentals of life.

If you know how a radio works, you should be able to take it apart and put it back together, Richardson says. Same goes for genetics.

Already, the team has gained a huge understanding of what yeast genes are necessary for keeping it alive and which are bloatware. And theyve learned a lot from trial and error: Small changes to the genetic code have made the difference between a cell that thrives and a cell that dies.

2) It paves the way for further genetically engineering yeast.

If you think of yeast as a factory, then its genome is the operating system. The engineered yeast will be a well-understood platform upon which to build extra functions, like generating biofuels or manufacturing pharmaceuticals.

Yeast is already extremely useful. Brewers use it convert sugar into alcohol in beer. Bakers use it to turn a mass of flour into pillowy, tender bread. If scientists can reengineer yeast from scratch, they can teach it a few more tricks.

We wanted to make changes that are very difficult to make without rebuilding it from the ground up, Richardson says.

The scientists have designed some new programs into the genome. One is called a scramble function. With a push of a button essentially, this is a simplification scientists will be able to instantly mutate their synthetic genome into a million new forms.

The analogy is if you had a million decks of cards, there would be one that would give you the best hand at gin rummy, there would be another that would give you the best hand at Texas Holdem, and so on, says Jef Boeke, an NYU biochemist and one of the leads of the Sc2.0 project.

And then they could look through those randomized yeast cells for ones that might be handy. Some could, for instance, produce higher concentrations of alcohol from sugar (which is useful in producing biofuel, or beverages). Others could be more adept at breaking down certain proteins.

Also, in the Sc2.0 design, the biologists have done some tidying up of the genome. Genes that do something similar often are not grouped together in one location like someone organized would do it, Joel Bader, a Johns Hopkins biomedical engineer who oversaw much of the project, explains.

1) Design the chromosomes on computers.

The scientists are editing an existing genome, rather than dreaming up a genome from scratch.

So they start with the text of a fully sequenced yeast chromosome on a computer, and make little tweaks. Most of the changes are to make the genomes more resistant to mutations. That way nature wont as easily erase any changes scientists engineer in the future.

The scientists also took out introns, filler regions of the DNA that dont code for anything at all. And they took special pains to mark genes that yeast need to survive. You have to be careful around them, Richardson says.

2) Make sure the designs can actually be built.

An architect can draw the most beautiful building her mind can imagine. But if an engineer says it cant be built, it cant be built.

A similar thing happens with DNA design. The chromosomes have to be assembled from tiny pieces of DNA, and they have to get glued together at very specific points. In your design, you want to plan ahead for where those junctions are, she says. Or certain snippets of DNA just wont stick together during assembly.

3) Manufacture the DNA

Each one of the 16 yeast chromosomes can contain 100,000 base pairs of DNA. But there is no DNA printer that can perfectly spit out that many in a stable chain.

So the scientists have to manufacture the DNA in small chunks 60 or 100 base pairs. Every letter has to be synthesized and then checked against our design to make sure we dont have any mistakes, she says.

Lab workers can then assemble around 10 or so of these chunks into 600-base-pair pieces of DNA. Then they glue those larger pieces together and so on until they have large 10,000 base-pair chains.

4) Replace natural chromosomes with synthetic ones

In a painstaking process that provides a critical safety check, the new synthetic chromosome is inserted in pieces rather than all at once. If any piece kills the cell, they know theres a problem in that section of the code.

5) Combine all the synthetic chromosomes into one yeast cell.

The previous four steps are what it takes just to produce one chromosome. Yeast has 16 total.

For a time, each of those 16 chromosomes will live in a separate yeast strain. (That is, one yeast cell will have a synthetic version of chromosome 1, with the rest being natural. Another will have a synthetic version of only chromosome 2 and so on).

In another painstaking process, the scientists will have to carefully breed the yeasts with each other so that all 16 synthetic chromosomes (plus one extra, completely new chromosome) all end up in the same cell together.

I asked several of the scientists if, when this is all done, they will have created a new species altogether. Thats up for debate, they say. The yeast 2.0 will look like and function like a normal yeast cell. But theres a chance it wont be able to mate with a naturally occurring yeast cell (reproductive compatibility is a traditional definition of a species).

Overall, the scientists stress the wrong conclusion is that theyre creating life.

Were not starting with a bunch of inanimate chemicals, mixing chemicals, and having life pop out, Boeke says. We start with a living cell, and we replace the DNA that is inside.

But theyre doing something thats just as intriguing. No, theyre not creating life. Theyre transfiguring it.

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Scientists rewrote the DNA of an entire species - Vox

The sister of a Brockton woman murdered by a serial rapist and killer said a composite sketch based on his DNA gives her new hope the suspect will be caught before he strikes again.

Its amazing. I didnt think it was going to happen, Carol Peters told the Herald last night, more than two years after the skeletal remains of her sister, Linda Schufeldt, were discovered in the woods together with the body of Ashley Mylett on Dec. 28, 2014.

Nothings going to bring her back, but if they catch him, it will make such a difference not only for us, but also for the other women and their families and keep him from doing it again, Peters said from her Kansas home.

State police detectives and Brockton police have received numerous tips since Tuesday, when Plymouth District Attorney Timothy J. Cruz released a computer-generated composite sketch of the wanted man.

The startlingly lifelike image shows a brown- or light-brown-skinned man with black hair and black or brown eyes who has been forensically linked to the two murders, as well as three rapes that were committed in October and November 2013 and January 2014 in Brockton.

The calls have been continuous, Beth Stone, Cruzs spokeswoman, said yesterday. Were hopeful this sketch will jog someones memory.

DNA results all came back positive for the same suspect from each of the rapes, the district attorney said.

The body of Mylett and skeletal remains of Schufeldt were discovered together behind 251 N. Quincy St. in Brockton. As part of the investigation, DNA was extracted from one of the women and, after analysis by the State Police Crime Lab, it was determined to be a match with the DNA from the three rape cases.

Cruz recently contacted Parabon NanoLabs in Virginia to conduct Snapshot DNA phenotyping. Parabon used the DNA sample to predict the suspects physical appearance and develop a computer-generated composite sketch. The technology uses the DNA to accurately predict eye, hair and skin color.

Peters said shes still haunted by the death of her then-50-year-old sister.

I still dont know how she was murdered, whether she suffered, she told the Herald. She had some issues but she was a wonderful person and I love her and miss her.

Peters said she never lost hope and only a month or two ago got a tattoo with the words RIP Linda etched on her left shoulder so that I have her with me every day.

She was living life the best she could. Sometimes she lived in her car, the sister added. She worried about me before she worried about herself.

Peters said her sister, who served in the Navy and had five children, turned to prostitution as a last resort to feed her drug addiction.

She did what she had to do to get by, the sister added. A lot of people think thats a horrible thing, but unless youve lived in that persons shoes, you have no way of knowing.

But when her sisters body was found six months after she went missing, Peters said she was devastated.

I was hoping shed be found alive.

The DA is asking anyone with tips to call state or Brockton police at 508-894-2584.

More here:
DNA used to create suspect sketch - Boston Herald

Technology

Quick and inexpensive DNA sampling of a river, stream, or lake can now divulge what fish or other animals live there. This rapidly growing environmental DNA, or eDNA, technology is proving to be a game-changing conservation tool.

By JimRobbins March9,2017

A U.S. Forest Service technician heads out to the Blackfoot River in western Montana and pumps water through a small filter, five liters every time she stops. In a single day, she gathers dozens of samples, bringing back to the lab each of the fine mesh filters that the river water passed through.

U.S. Forest ServicebiologistMichaelSchwartz gathers water to be sampled for eDNAfrom Rattlesnake Creek in Montana. Kellie Carim/U.S. Forest Service

The filters contain DNA for species whether brook trout, stone flies, wood ducks, or river otters that have swum in that stream in the last day or two, up to a kilometer above the sample site. Every insect, fish, or animal continually sloughs off bits of its DNA in its feces or from its skin and just a single cell of the invisible, free-floating genetic material can tell researchers which species are present in a river or other water body.

Environmental DNA, or eDNA, is at the center of a brand new kind of fish and wildlife biology, and it is such a powerful tool that its transforming the field. eDNA was first used to detect invasive bullfrogs in France a decade ago. It was used in North America for the first time in 2009 and 2010 to detect invasive Asian carp in and around the Great Lakes. Since then, its use has grown exponentially, primarily in marine and freshwater environments.

You cant manage a species if you dont know where it is even 80-pound Asian carp, because you cant see them underwater, said Cornell University biologist David Lodge, who participated in the Asian carp study. So eDNA is particularly powerful in aquatic systems.

The DNA is so easy and inexpensive to gather and assay $50 to $150 to test each sample that the U.S. Forest Service has launched a project to collect DNA from all rivers and streams across the western U.S. to create an Aquatic Environmental DNA Atlas.

Environmental DNA is turning out to be an amazing tool in allowing us to detect the distribution of species, a distribution that has been invisible to us in the past, said Michael K. Schwartz, director of the Forest Services National Genomics Center for Wildlife and Fish Conservation in Missoula, Montana. It has remarkable efficiency.

Experts say use of the technology is in its early stages and that as it evolves it will become even more powerful, providing an even deeper look into the genetics of aquatic ecosystems, including ocean environments.

The next step in the evolution of the technology would be to estimate the abundance of a species in a river or other water body based on the quantity of DNA found in samples. That is going to continue to be a research frontier, said Lodge.

Scientists say that eDNA can be used not only to detect the presence of invasive species in a river, lake, or ocean, but also to help reintroduce native species, to study genetic diversity among fish stocks, and to better manage commercial and endangered species.

Until now, the primary way to conduct distribution studies was to physically see, count, and describe species, a time-consuming process that is expensive and often hit-or-miss. That leaves huge gaps in the knowledge of where species are, which often confounds species management.

One of the best examples of the transformative nature of eDNA is in assessing the distribution of bull trout across its entire range. Bull trout are a threatened species in the U.S. Northwest, and their habitat is declining because of deteriorating water quality and warming water temperatures. Cold water is essential to their spawning.

By knowing where the fish live, managers can direct funding for protecting and restoring riparian habitat. Until recently, though, the only way to find and count bull trout was to do an electro-shocking census. That means a biologist would take equipment to the river to shock fish in the water and count them as they float, stunned, to the surface. That technique is time-consuming, not always permitted, and can survey only a fairly small area with each census.

With eDNA, a single sample can tell which species have been in a river a kilometer upstream from the sample site within the last 24 to 40 hours thats how long the DNA lasts in the water. Tests with caged fish have shown that just three fish in a river can give a 100 percent detection rate, and one fish 85 percent.

The range-wide bull trout study, conducted by the Forest Service, first looked at the temperature of streams that fit bull trout requirements. Then eDNA samples were taken to detect the trouts presence in those reaches. Weve been able to detect bull trout in streams in a matter of days that have taken some of our colleagues years to confirm, says Schwartz. And there were surprises. In a couple of locations where bull trout were not supposed to be, we have multiple detections throughout the drainage, Schwartz says.

Researchers have used eDNA testing to assess populations of bull trout, a threatened species in the U.S. Northwest. Wade Fredenberg/USFWS

eDNA technology is being used in other parts of the world as well.

In the Dinaric Alps, a mountain range that runs through Croatia and Slovenia, theres a curious creature called the olm a blind, flesh-colored salamander also known as a baby dragon that lives its entire life underground. They are a symbol of our country, but are still as mysterious as they were a hundred years ago, Peter Trontelj of the Department of Biology at the Ljubljana Faculty of Biotechnology told an English-language news site. The only way to know where they lived was to dive into a cave and find them or to see them washed out of a cave after a heavy rain. But after testing for eDNA, biologists confirmed their presence in 10 caves where they were known to exist, and discovered new populations in five others.

In Japan last year, scientists found that eDNA sampling gave them a rough snapshot of the distribution and biomass of fish species in a bay in the Sea of Japan.

eDNA assessment has also become a new, powerful weapon in the fight against invasive species.

The first published study of the use of eDNA for conservation purposes was in 2008 in France. The American bullfrog has become an invasive species in France and around the world; not only does it displace native species, but the bullfrog also carries the virulent amphibian killer fungus, chytrid. Early detection of bullfrogs can make a big difference in the ease of eradicating them, but they are hard to find. Calling the frogs only locates a small portion of the population and even then the census needs to be done at night and in certain weather conditions. With eDNA, French researchers were able to easily confirm the bullfrogs presence in some ponds and target those for removal.

The identification of fugitive DNA is also playing a role in the detection and eradication of invasive fish, a growing problem. Asian carp, a voracious plankton eater, would pose a huge threat to the ecology of the Great Lakes if they become established there, since they eat so much plankton they starve young fish of other species. While a few have been detected, biologists are monitoring rivers and canals that feed the lakes for early signs of more invaders.

In the western U.S., one target of eDNA searches has been brook trout, an interloper from the East that outcompetes native species. In one eradication scenario, managers would capture native fish and then use poison to kill the brook trout, so that native species could be re-introduced. If biologists find brook trout DNA after poisoning a river, they could go back in and electrofish to see where the stragglers may be hiding.

Sometimes they have detected one or two or three fish finding refuge in a side channel, said Schwartz. In one case they found a dead brook trout under a rock that didnt flush out of the system.

Thats one of the drawbacks of the technology theres no way to tell if the DNA of an invasive species is dead or alive. A great deal of time and effort could be spent trying to find an exotic carp, for example, that was already dead.

The ease and low cost of collecting samples has enabled widespread use of the powerful technique and eDNA can be gathered by just about anyone. It would be prohibitive to test all of New York states 7,600 lakes and 70,000 miles of rivers and streams for invasive species. So researchers at Cornell University send detection kits to schools across New York as a citizen science project. Students gather water samples as part of their science class and ship the filters to the university. When the results are returned, the students enter them in a database.

Any group of students can collect samples in lakes, rivers, and ponds, said Donna Cassidy-Hanley, a senior research associate at the Cornell University College of Veterinary Medicine. Once the data is plotted, the people doing the eradication work can see where the species has spread.

Students recently found DNA from the round goby, an aggressive invasive fish, and confirmed its presence in Oneida Lake in the Finger Lakes, where it was not known to exist. It sets the stage for corrective action, Cassidy-Hanley said.

As new techniques evolve, a single water sample will be sufficient to detect which communities of organisms exist in a waterway or in the ocean. In the future, write Phillip Francis Thomsen and Eske Willerslev, two Danish experts from the Center for GeoGenetics at the Natural History Museum of Denmark, we expect the eDNA approaches to move from single-marker analysis of species or communities to meta-genomic surveys of entire ecosystems to predict spatial and temporal biodiversity. That would greatly enhance conservation efforts.

One of the problems facing conservation biology these days is that not all populations within a species have the same DNA. Some populations of bull trout might be better adapted to surviving in warmer water, for example, or even adapted to specific drainages. If the DNA for those adaptations are known and in most cases they arent yet then finding certain specially adapted populations to be relocated or protected will be a lot quicker and easier with eDNA.

This technique will help solve a lot of the problems of conservation across broad scales, said Schwartz.

Jim Robbins is a veteran journalist based in Helena, Montana. He has written for the New York Times, Conde Nast Traveler, and numerous other publications.His latest book,The Wonder of Birds: What they Tell Us about the World, Ourselves and a Better Future, is due out in May. More about Jim Robbins

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A Splash of River Water Now Reveals the DNA of All Its Creatures - Yale Environment 360

In this file photo, a girl goes nose-to-nose with a Neanderthal statue at a museum in Germany.

Neanderthal Museum (Mettmann, Germany)

What exactly did Neanderthals eat to survive?

The answer varies wildly depending on where they lived, and a new study published Wednesday in the journal Nature reveals vivid new details about the dietary habits of our distant, prehistoric cousins. It also found evidence that Neanderthals figured out how to medicate their illnesses and injuries with substances found in nature.

An international team of researchers sequenced the DNA from hardened plaque on the teeth of five Neanderthal specimens from three different sites across Europe and analyzed the results to try to unravel long-running mysteries about Neanderthals diet and health. The five Neanderthals included two individuals from El Sidrn cave in Spain, two found in the Spy cave in Belgium, and one individual from Breuil Grotta in Italy.

Their findings are illuminating, and demonstrate dramatic geographic differences in the Neanderthal diet.

For instance, the Neanderthals who lived in what is now Belgium apparently ate plenty of meat, including woolly rhinoceros and wild sheep.

However, the Neanderthals from El Sidrn, Spain, showed zero signs of meat consumption; instead they got nourishment from foods like pine nuts, moss and mushrooms gathered from the forest.

The upper jaw of a Neanderthal from El Sidron, Spain. A dental calculus (plaque) deposit is visible on the rear molar at right. DNA analysis reveals this individual was eating poplar, a source of aspirin, and had also consumed moulded vegetation including Penicillium fungus, source of a natural antibiotic.

Paleoanthropology Group MNCN-CSIC

The analysis also peeled back the curtain on how Neanderthals coped with sickness.

For instance, one of the Neanderthals from Spain appeared to have a dental abscess and stomach bug and was self-medicating with poplar, a natural painkiller containing salicylic acid, the same active ingredient in the aspirin you may have popped last week. The individual had also consumed the antibiotic-producing moldPenicillium tens of thousands of years before Dr. Alexander Fleming used a strain of Penicilliumto develop the first antibiotic, revolutionizing modern medicine.

The study adds another layer to Neanderthal history, which to this day has significant holes that confound scientists.

Neanderthal diet remains a topic of considerable debate, with limited data on the specific animals and plants directly consumed or the potential effects on Neanderthal health and disease, the researchers wrote.

Neanderthals are humans closest known, extinct hominin relatives. Theyco-existed and even interbred with ourmodern human ancestors in the Late Pleistocene age, then disappeared from Europe around 40,000 years ago, although extinction patterns beyond Europe across Eurasia are still ambiguous.

Working in the Tunnel of Bones cave, in El Sidron, Spain, where 12 Neanderthal specimens dating around 49,000 years ago have been recovered.

Paleoanthropology Group MNCN-CSIC; Photo by Antonio Rosas

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DNA reveals what Neanderthals ate and how they self-medicated - CBS News