Daily Archives: August 1, 2017

August 1, 2017

For the first time, researchers have used whole genome sequencing to identify the cause of a zoonotic infection that sparked a national epidemic. In a study published this week in mBio, an open-access journal of the American Society for Microbiology, researchers describe their use of whole genome sequencing to determine the cause of a respiratory disease that ripped through a population of native horses in Iceland several years ago.

"Our study showed that you can use genomic sequencing to tell epidemic strains from endemic strains," said principal study investigator Andrew Waller, PhD, head of bacteriology, Animal Health Trust, Suffolk, United Kingdom.

The Icelandic horse population is geographically isolated, arising from animals introduced by settlers in the ninth and tenth centuries. Virtually no horses have been imported in the last thousand years. This isolation has kept Icelandic horses free from the most common contagious equine diseases. In 2010, a respiratory disease of unknown origin spread through almost the entire population of 77,000 native horses in Iceland. The disease involved coughing, nasal discharge, and high morbidity. "Iceland was so worried about what was causing it that they stopped exporting horses to the rest of the world," said Dr. Waller. "It had a big impact on their economy, as they breed and sell a lot of horses each year."

A team of scientists at the University of Reykjavik performed microbiological investigations and ruled out known viral agents, but identified the gram-positive bacterium Streptococcus zooepidemicus from almost all of the nasal swabs taken from coughing horses and from the diseased tissues of occasional fatal cases. The bacteria is routinely isolated from healthy horses and widely considered to be commensal, but because it was so ubiquitous during the outbreak, the researchers began to think it could be the culprit.

Scientists at the Wellcome Trust Sanger Institute performed whole genome sequencing on 305 isolates of S. zooepidemicus: 257 from the epidemic including from 100 horses, two cats, one dog, and three people. They compared the recent isolates to ten archived Icelandic isolates of S. zooepidemicus from seven horses, two sheep and a dog to provide insight into the identity of historical isolates of S. zooepidemicus from Iceland, and to 38 isolates, which represented the wider population diversity of the bacteria beyond Iceland.

The majority of S. zooepidemicus isolates recovered during the epidemic fell into four distinct clades. "ST209 stood out as likely to be responsible for the epidemic," said Dr. Waller. The epidemic ST209 strain was also recovered from a cat and the blood sample of an Icelandic woman who had suffered a miscarriage.

Network analysis of affected farms identified a single common training yard as a primary center of transmission and demonstrated how a novel strain can spread rapidly through a susceptible population devoid of sufficient cross-protective immunity, despite a background of concomitant colonization with endemic strains. The most likely route of transmission of the epidemic strain at this yard, a water treadmill that horses used on a daily basis, did not contain disinfectant and was changed on a once- or twice-weekly basis. This provided ideal conditions for the transmission of S. zooepidemicus between visiting horses. Adding chlorine coupled with regular cleaning and disinfection of water treadmills may minimize or eliminate the transmission of S. zooepidemicus or other infectious agents via this route.

Previously, researchers have used whole genome sequencing to determine how germs spread through a hospital, but this is the first time the technology has been used to track the outbreak of a zoonotic disease. "This study enabled us to identify which strains were normally present in the Icelandic horse population and which was the epidemic strain that was causing the problem and that is very new," said Dr. Waller. "It was great to be able to show that this particular strain had spread so quickly through the whole population, and as far as we are aware, that has not been done before using whole genome sequencing."

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The University of Adelaide is investigating the respiratory health of South Australia's horses and their owners to see if there is undiagnosed asthma-like disease in Australia's equine population.

The first flower to appear along the path of plant evolution, during the time of the dinosaurs, was a hermaphrodite with petal-like organs arranged in concentric circles, researchers said Monday.

A new study from Harvard T.H. Chan School of Public Health and Howard Hughes Medical Institute sheds light on how a key fat-producing enzyme helps protect cells from a toxic form of fat.

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Size matters in the carrion world, and so do habitat and temperature.

Evolution doesn't have to take millions of years. New research shows that a type of lizard living on man-made islands in Brazil has developed a larger head than its mainland cousins in a period of only 15 years.

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Whole genome sequencing identifies cause of zoonotic epidemic - Phys.Org

Parsing the creatures 2 billion base pairs, Feschotte and his colleagues did stumble on something strange. We found some very weird transposons, he said. Because these oddball parasite sequences didnt appear in other mammals, they were likely to have invaded after bats diverged from other lineages, perhaps picked up from an insect snack some 30 to 40 million years ago. Whats more, they were incredibly active. Probably 20 percent or more of the bats genome is derived from this fairly recent wave of transposons, Feschotte said. It raised a paradox because when we see an explosion of transposon activity, wed predict an increase in size. Instead, the bat genome had shrunk. So we were puzzled.

There was only one likely explanation: Bats must have jettisoned a lot of DNA. When Kapusta joined Feschottes lab in 2011, her first project was to find out how much. By comparing transposons in bats and nine other mammals, she could see which pieces many lineages shared. These, she determined, must have come from a common ancestor. Its really like looking at fossils, she said. Researchers had previously assembled a rough reconstruction of the ancient mammalian genome as it might have existed 100 million years ago. At 2.8 billion base pairs, it was nearly human-size.

Next, Kapusta calculated how much ancestral DNA each lineage had lost and how much new material it had gained. As she and Feschotte suspected, the bat lineages had churned through base pairs, dumping more than 1 billion while accruing only another few hundred million. Yet it was the other mammals that made their jaws drop.

Mammals are not especially diverse when it comes to genome size. In many animal groups, such as insects and amphibians, genomes vary more than a hundredfold. By contrast, the largest genome in mammals (in the red viscacha rat) is only five times as big as the smallest (in the bent-wing bat). Many researchers took this to mean that mammalian genomes just dont have much going on. As Susumu Ohno, the noted geneticist and expert in molecular evolution, put it in 1969: In this respect, evolution of mammals is not very interesting.

But Kapustas data revealed that mammalian genomes are far from monotonous, having reaped and purged vast quantities of DNA. Take the mouse. Its genome is roughly the same size it was 100 million years ago. And yet very little of the original remains. This was a big surprise: In the end, only one-third of the mouse genome is the same, said Kapusta, who is now a research associate in human genetics at the University of Utah and at the USTAR Center for Genetic Discovery. Applying the same analysis to 24 bird species, whose genomes are even less varied than those of mammals, she showed that they too have a lively genetic history.

No one predicted this, said J. Spencer Johnston, a professor of entomology at Texas A&M University. Even those genomes that didnt change size over a huge period of time they didnt just sit there. Somehow they decided what size they wanted to be, and despite mobile elements trying to bloat them, they didnt bloat. So then the next obvious question is: Why the heck not?

Feschottes best guess points at transposons themselves. They provide a very natural mechanism by which gain provides the template to facilitate loss, he said. Heres how: As transposons multiply, they create long strings of nearly identical code. Parts of the genome become like a book that repeats the same few words. If you rip out a page, you might glue it back in the wrong place because everything looks pretty much the same. You might even decide the book reads just fine as is and toss the page in the trash. This happens with DNA too. When its broken and rejoined, as routinely happens when DNA is damaged but also during the recombination of genes in sexual reproduction, large numbers of transposons make it easy for strands to misalign, and that slippage can result in deletions. The whole array can collapse at once, Feschotte said.

This hypothesis hasnt been tested in animals, but there is evidence from other organisms. Its not so different from what were seeing in plants with small genomes, Leitch said. DNA in these species is often dominated by just one or two types of transposons that amplify and then get eliminated. The turnover is very dynamic: in 3 to 5 million years, half of any new repeats will be gone.

Thats not the case for larger genomes. What we see in big plant genomes and also in salamanders and lungfish is a much more heterogeneous set of repeats, none of which are present in [large numbers], Leitch said. She thinks these genomes must have replaced the ability to knock out transposons with a novel and effective way of silencing them. What they do is, they stick labels onto the DNA that signal to it to become very tightly condensed sort of squished so it cant be read easily. That alteration stops the repeats from copying themselves, but it also breaks the mechanism for eliminating them. So over time, Leitch explained, any new repeats get stuck and then slowly diverge through normal mutation to produce a genome full of ancient degenerative repeats.

Meanwhile, other forces may be at play. Large genomes, for instance, can be costly. Theyre energetically expensive, like running a big house, Leitch said. They also take up more space, which requires a bigger nucleus, which requires a bigger cell, which can slow processes like metabolism and growth. Its possible that in some populations, under some conditions, natural selection may constrain genome size. For example, female bow-winged grasshoppers, for mysterious reasons, prefer the songs of males with small genomes. Maize plants growing at higher latitudes likewise self-select for smaller genomes, seemingly so they can generate seed before winter sets in.

Some experts speculate that a similar process is going on in birds and bats, which may need small genomes to maintain the high metabolisms needed for flight. But proof is lacking. Did small genomes really give birds an advantage in taking to the skies? Or had the genomes of birds flightless dinosaur ancestors already begun to contract for some other reason, and did the physiological demands of flight then shrink the genomes of modern birds even more? We cant say whats cause and effect, Suh said.

Its also possible that genome size is largely a result of chance. My feeling is theres one underlying mechanism that drives all this variability, said Mike Lynch, a biologist at Indiana University. And thats random genetic drift. Its a principle of population genetics that drift whereby a genetic variant becomes more or less common just by sheer luck is stronger in small groups, where theres less variation. So when populations decline, such as when new species diverge, the odds increase that lineages will drift toward larger genomes, even if organisms become slightly less fit. As populations grow, selection is more likely to quash this trait, causing genomes to slim.

None of these models, however, fully explain the great diversity of genome forms. The way I think of it, youve got a bunch of different forces on different levels pushing in different directions, Gregory said. Untangling them will require new kinds of experiments, which may soon be within reach. Were just at the cusp of being able to write genomes, said Chris Organ, an evolutionary biologist at Montana State University. Well be able to actually manipulate genome size in the lab and study its effects. Those results may help to disentangle the features of genomes that are purely products of chance from those with functional significance.

Many experts would also like to see more analyses like Kapustas. (Lets do the same thing in insects! Johnston said.) As more genomes come online, researchers can begin to compare larger numbers of lineages. Four to five years from now, every mammal will be sequenced, Lynch said, and well be able to see whats happening on a finer scale. Do genomes undergo rapid expansion followed by prolonged contraction as populations spread, as Lynch suspects? Or do changes happen smoothly, untouched by population dynamics, as Petrovs and Feschottes models predict and recent work in flies supports?

Or perhaps genomes are unpredictable in the same way life is unpredictable with exceptions to every rule. Biological systems are like Rube Goldberg machines, said Jeff Bennetzen, a plant geneticist at the University of Georgia. If something works, it will be done, but it can be done in the most absurd, complicated, multistep way. This creates novelty. It also creates the potential for that novelty to change in a million different ways.

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Shrinking Bat DNA and Elastic Genomes - Quanta Magazine

July 31, 2017 Credit: CC0 Public Domain

In collaboration with scientists from the U.K., Europe, Japan and the United States, researchers at the Human Genome Sequencing Center at Baylor College of Medicine have discovered a whole genome duplication during the evolution of spiders and scorpions. The study appears in BMC Biology.

Researchers have long been studying spiders and scorpions for both applied reasons, such as studying venom components for pharmaceuticals and silks for materials science, and for basic questions such as the reasons for the evolution and to understand the development and ecological success of this diverse group of carnivorous organisms.

As part of a pilot project for the i5K, a project to study the genomes of 5,000 arthropod species, the Human Genome Sequencing Center analyzed the genome of the house spider Parasteatoda tepidariorum a model species studied in laboratories and the Arizona bark scorpion Centruroides sculpturatus, the most venomous scorpion in North America.

Analysis of these genomes revealed that spiders and scorpions evolved from a shared ancestor more than 400 million years ago, which made new copies of all of the genes in its genome, a process called whole genome duplication. Such an event is one of the largest evolutionary changes that can happen to a genome and is relatively rare during animal evolution.

Dr. Stephen Richards, associate professor in the Human Genome Sequencing Center, who led the genome sequencing at Baylor, said, "It is tremendously exciting to see rapid progress in our molecular understanding of a species that we coexist with on planet earth. Spider genome analysis is particularly tricky, and we believe this is one of the highest quality spider genomes to date."

Similarly, there also have been two whole genome duplications at the origin of vertebrates, fuelling long-standing debate as to whether the duplicated genes enabled new biological complexity in the evolution of the vertebrate lineage leading to mammals. The new finding of a whole genome duplication in spiders and scorpions therefore provides a valuable comparison to the events in vertebrates and could help reveal genes and processes that have been important to our own evolution.

"While most of the new genetic material generated by whole genome duplication is subsequently lost, some of the new gene copies can evolve new functions and may contribute to the diversification of shape, size, physiology and behavior of animals," said Dr. Alistair McGregor, professor of evolutionary developmental biology at Oxford Brookes University and lead author of the research. "Comparing the whole genome duplication in spiders and scorpions with the independent events in vertebrates reveals a striking similarity. In both cases, duplicated clusters of Hox genes have been retained. These are very important genes that regulate development of body structures in all animals, and therefore can cause evolutionary changes in animal body plans."

The study also found that the copies of spider Hox genes show differences in when and where they are expressed, suggesting they have evolved new functions.

McGregor explains that these changes may help clarify the evolutionary innovations in spiders and scorpions including specialized limbs and how they breathe, as well as the production of different types of venom and silk, which spiders use to capture and kill their prey.

"Many people fear spiders and scorpions, but this research shows what a beautiful part of the evolutionary tree they represent," said Dr. Richard Gibbs, director of the Human Genome Sequencing Center and the Wofford Cain Chair and professor of molecular and human genetics at Baylor.

"Costs have now dropped rapidly enough from tens of millions of dollars to merely a few thousand dollars for this genomic analyses to now be performed on any species," Richards said. "There is still so much more to learn about the life on earth around us, and I believe this result is just the beginning of understanding the molecular make up of spiders."

Explore further: Flowers' genome duplication contributes to their spectacular diversity

More information: Evelyn E. Schwager et al. The house spider genome reveals an ancient whole-genome duplication during arachnid evolution, BMC Biology (2017). DOI: 10.1186/s12915-017-0399-x

Scientists at the University of Bristol have shed new light on the evolution of flowers in research published today in the Royal Society journal Proceedings of the Royal Society B.

New biological information gleaned from the red vizcacha rat, a native species of Argentina, demonstrates how genomes can rapidly change in size.

According to the '2R hypothesis', the evolution of modern vertebrates was propelled forward in part by two events in our early ancestry in which the entire genome was duplicated. These events, known as 1R and 2R, yielded ...

Spider silks, the stuff of spider webs, are a materials engineer's dream: they can be stronger than steel at a mere fraction of weight, and also can be tougher and more flexible. Spider silks also tend not to provoke the ...

Sequencing and comparative analysis of the genome of the Western Orchard predatory mite has revealed intriguingly-extreme genomic evolutionary dynamics through an international research effort co-led by scientists from the ...

For decades, the story of spider evolution went like this: As insects became more and more diverse, with some species taking to the skies, spiders evolved new hunting strategies, including the ability to weave orb-shaped ...

The first flower to appear along the path of plant evolution, during the time of the dinosaurs, was a hermaphrodite with petal-like organs arranged in concentric circles, researchers said Monday.

A new study from Harvard T.H. Chan School of Public Health and Howard Hughes Medical Institute sheds light on how a key fat-producing enzyme helps protect cells from a toxic form of fat.

Random differences between cells early in development could be the key to making different cells in the body, according to new research from a team co-led by Professor Wolf Reik. Different cell types - brain, blood, skin, ...

Size matters in the carrion world, and so do habitat and temperature.

Scientists examining the multiple eyes found on the tentacles of fan worms have discovered they evolved independently from their other visual systems, specifically to support the needs of their lifestyle.

Snowshoe hares in Pennsylvaniaat the southern end of the species' rangeshow adaptations in fur color and characteristics, behavior and metabolism, to enable them to survive in less wintry conditions than their far northern ...

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Rare whole genome duplication during spider evolution could ... - Phys.Org

Horizon Discovery (Horizon or the Company), a leader in the application of gene editing technologies, announced it has released a complete, high-quality, well annotated sequence of its GS Knockout CHO-K1 bioproduction cell line. The sequence will be made available publicly via the Ensembl website at EMBL-EBI, to serve the community as a resource to drive research and innovation in bioproduction at Horizon and across the industry.

Genome sequence is based on Horizons Glutamine Synthetase (GS) Knock-Out CHO K1 manufacturing-ready cell line.

Sequenced in collaboration with the Wellcome Trust Sanger Institute, this high value reference tool enables the industry to screen for genes associated with desired phenotypes and to help drive innovation in bioproduction.

Horizon commissioned Eagle Genomics to complete the high quality genome assembly and gold standard gene annotation of the data for the project using their cutting-edge technology in close collaboration with the Ensembl group at the European Bioinformatics Institute (EMBL-EBI).

Over the past 30 years, the pharmaceutical industry has substantively redesigned every part of the bioproduction process, considerably improving productivity. However, in this time the CHO cell itself, arguably the greatest potential source of efficiency improvements, has remained largely unchanged.

The CHO genome was first sequenced in 2011; however, the current annotation is not suitable for whole-genome screening. Together with licensing terms that restrict modification of the cells, this has meant that progress in cell-line improvement has been slow. This has been a source of considerable frustration among drug manufacturers, as there has been increasing interest in improving productivity through cell-line innovation since the emergence of gene-editing tools such as CRISPR.

To address this problem, Horizon and its partners the Sanger Institute and Eagle Genomics - have established a high-quality sequence map based on Horizons GS Knock-Out CHO K1 cell line. By releasing this sequence into the public domain, Horizon hopes to enable genuine quality-by-design in bioproduction cell-line development, through the widespread ability to identify genes that, if modified, could improve the phenotype of interest.

Horizons GS Knock-Out CHO K1 cell line was chosen as the basis for this project as it is manufacturing-ready, and licenses come with the right to modify the cells, which is highly unusual among commercially available GS CHO KO cells. The use of Horizons cells alongside the public sequence thereby provides the ideal base and dataset to enable screening that can provide immediately actionable results. The public sequence can also be applied to any other CHO cell line; however, additional validation of sequence may be required to confirm the cell line being used does not differ in any meaningful way from the public sequence.

The sequencing project was undertaken as part of the Biocatalyst Funding awarded jointly to Horizon, University of Manchester and the Centre for Process Innovation (CPI). The Biocatalyst Funded project is focused primarily on large-scale gene editing to improve CHO host performance, which in turn required specific high-resolution sequencing of the Horizon GS knockout CHO host. To achieve this, Horizon collaborated with the Sanger Institute to achieve the detailed genome sequencing needed, and selected Eagle Genomics to deliver the complex annotation of the genome assembly.

This sequence empowers Horizons continuous innovation process, supporting the identification of targets that may lead to future iterations of the cell line. Additionally, Horizon has developed a range of services to directly support customers internal efficiency improvement efforts.

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Horizon Releases High Quality, Well Annotated CHO Genome ... - Technology Networks

Scientists have long been able to make specific changes in the DNA code. Now, theyre taking the more radical step of starting over, and building redesigned life forms from scratch. [Jef Boeke], a researcher at New York University, directs an international team of 11 labsworking to rewrite the yeast genome.

Their work is part of a bold and controversial pursuit aimed at creating custom-made DNA codes to be inserted into living cells to change how they function, or even provide a treatment for diseases. It could also someday help give scientists the profound and unsettling ability to create entirely new organisms.

Also on the horizon is redesigning human DNA. Thats not to make genetically altered people, scientists stress. Instead, the synthetic DNA would be put into cells, to make them better at pumping out pharmaceutical proteins, for example, or perhaps to engineer stem cells as a safer source of lab-grown tissue and organs for transplanting into patients.

The cutting edge for redesigning a genomeis yeast. Its genome is bigger and more complex than the viral and bacterial codes altered so far. But its well-understood and yeast will readily swap man-made DNA for its own.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Scientists build DNA from scratch to alter lifes blueprint

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Life's DNA blueprint: Rewriting yeast genome could help design ... - Genetic Literacy Project