Tag Archives: gene

New study furthers our understanding of how genetics influence heavy drinking

A new study comes to flesh out our understanding of the genetic basis for problematic drinking.

Image via Pixabay.

Previously, we knew of 13 gene variants associated with heavy drinking. Now, this study expands our knowledge to an impressive 29 different gene variants linked to problematic alcohol use. One limitation of the study is that, despite its relatively large sample of 435,000 people, all of them were of European descent.

Bottoms up

“The new data triple the number of known genetic risk loci associated with problematic alcohol use,” said Joel Gelernter at Yale University School of Medicine, the Foundations Fund Professor of Psychiatry and a professor of genetics and neuroscience.

Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, who is the senior author of the multi-institutional study.

The study looked at genome-wide records of people of European ancestry contained in four separate biobanks and datasets. The team identified individuals who met criteria for problematic drinking, including alcohol use disorder and alcohol use with medical consequences and then looked for genetic variants they all shared.

They located 19 previously-unknown genes that represent risk factors for such behavior, alongside 10 previously-identified genes.

Furthermore, they looked at genetic risk factors for several psychiatric disorders including anxiety disorder and depression in the genomes. During the study, this step allowed them to analyze the genetic links between such disorders and heavy drinking. Major depressive disorder showed the greatest correlation to problematic drinking; risk-taking behavior, insomnia were also positively correlated with such behavior.

The genes identified in this study are particularly stable from a hereditary point of view in the brain (they’re more stable across generations) and in “evolutionarily conserved regulatory regions of the genome”, which suggests that they perform important functions in our metabolism. Exactly what these functions remain to be determined.

“This gives us ways to understand causal relations between problematic alcohol use traits such as psychiatric states, risk-taking behavior, and cognitive performance,” said Yale’s Hang Zhou, associate research scientist in psychiatry and lead author of the study. “With these results, we are also in a better position to evaluate individual-level risk for problematic alcohol use,” Gelernter said.

Heavy drinking is associated with adverse medical and social outcomes, so understanding which people are at risk for such behavior could help us better protect them.

The paper “Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits” has been published in the journal Nature Neuroscience.

The world’s first gene-engineered reptiles are all albinos

Researchers report producing the first gene-edited reptiles ever.

An albino lizard hatchling.
Image credits Doug Menke.

A new study reports on the use of CRISPR-Cas9 to create albino brown anole lizards (A. sagrei). No other team has successfully applied gene-editing techniques to reptiles. The study also shows that the gene-edited lizards can also pass the modified genes for albinism to their offspring.

CRISPy lizards

“For quite some time we’ve been wrestling with how to modify reptile genomes and manipulate genes in reptiles, but we’ve been stuck in the mode of how gene editing is being done in the major model systems,” says corresponding author Doug Menke, an associate professor at the University of Georgia.

“We wanted to explore anole lizards to study the evolution of gene regulation, since they’ve experienced a series of speciation events on Caribbean islands, much like Darwin’s finches of the Galapagos.”

In most model species (such as lab rats, for example) CRISPR-Cas9 is employed by injecting gene-editing vectors into freshly fertilized eggs or single-cell zygotes (i.e. after fertilization). However, this approach can’t be used on reptiles, as they employ an internal fertilization process making it hard to predict when an egg becomes fertilized. It’s also hard to isolate a single-celled embryo from momma lizard, which means we can’t transfer it out into a lab dish and work on it.

Menke and his team, however, noticed that the transparent membrane over the species’ ovary allowed them to track all of the developing eggs, including which eggs were going to be ovulated and fertilized next. They then decided to inject the CRISPR elements into unfertilized eggs within the ovaries.

“Because we are injecting unfertilized eggs, we thought that we would only be able to perform gene editing on the alleles inherited from the mother. Paternal DNA isn’t in these unfertilized oocytes,” Menke says.

He explains that it took three months for the lizards to hatch, and says that the procedure is “a bit like slow-motion gene editing”. By the end, the researchers found that about 6% to 9% of the oocytes, depending on their size, produced offspring with gene-editing events. Around half of the edited lizards held modified genes from both parents. The findings indicate that the CRISPR components remain active for several days, or even weeks, within the unfertilized eggs.

In some other model animals, CRISPR-Cas can have efficiencies up to 80% or higher, which would make the present 6% seem like a paltry amount, Menke explains.

“But no one has been able to do these sorts of manipulations in any reptile before,” he says. “There’s not a large community of developmental geneticists that are studying reptiles, so we’re hoping to tap into exciting functional biology that has been unexplored.”

The team decided to use albinism genes for the study because they result in an obvious physical trait (loss of pigmentation) without being lethal to the animal. Secondly, they wanted to use the lizards as a model to study how the loss of pigmentation impacts retina development, as humans with albinism often have vision problems. The anole lizards are ideally suited for this: their eyes have a fovea, a pit-like structure in the retina that underpins high-acuity vision, which humans share, but most of our main animal models lack.

Ultimately, this gene-editing technique could be translated for use in other animals, Menke adds.

“We never know where the next major insights are going to come from, and if we can’t even study how genes work in a huge group of animals, then there’s no way to know if we’ve explored everything there is to explore in the realm of gene function in animals,” Menke says.

“Each species undoubtedly has things to tell us, if we take the time to develop the methods to perform gene editing.”

The paper “CRISPR-Cas9 Gene Editing in Lizards through Microinjection of Unfertilized Oocytes” has been published in the journal Cell Reports.

Pancreas adenocarcinoma.

This one gene seems to underpin pancreatic cancers in mice

Turning off one gene could completely block pancreatic cancer.

Pancreas adenocarcinoma.

Pancreas adenocarcinoma.
Image credits Ed Uthman / Flickr.

Pancreatic cells work in some pretty hazardous conditions. So, they come equipped with a particular gene that allows them to switch back to a more ‘primitive’ state and divide to make up for any fallen colleagues. However, this process can also create the conditions for pancreatic cancers to develop — and one group of researchers is looking into how to prevent it from happening. The results far exceeded their expectations.

Under maintenance

“We found that deleting the ATDC gene in pancreatic cells resulted in one of the most profound blocks of tumor formation ever observed in a well-known mice model engineered to develop pancreatic ductal adenocarcinoma, or PDA, which faithfully mimics the human disease,” says corresponding author Diane Simeone, MD, director of the Pancreatic Cancer Center of NYU Langone Health’s Perlmutter Cancer Center.

“We thought the deletion would slow cancer growth, not completely prevent it.”

The study built on the theory that pancreatic cancers develop when adult cells switch back to high-growth cell types (acinar-to-ductal metaplasia or ADM) — like those that drive fetal development — to repair local tissues. If this reversion takes place in the presence of genetic errors, the repair process quickly goes haywire, leading to unchecked cellular proliferation — cancer.

Led by researchers from the NYU School of Medicine and the University of Michigan, Ann Arbor, the team found that the ATDC gene must be active for injured pancreatic cells to undergo reversion. They focused on a type of pancreatic cells called acinar cells. Acinar cells produce enzymes to support digestion and dump them in the small intestine via a network of ducts.

But, they don’t call them digestive enzymes for nothing — these compounds do damage the ducts and associated cells as they move towards the small intestine. It’s not particularly heavy damage, but it does build up over time. As such, acinar cells have evolved to easily switch back into stem-like cell types, as did pancreatic duct cells, in order to heal this damage. If they do undergo this repair process after acquiring random DNA changes (mutations), however, they are prone to becoming cancerous. Mutations of a gene called KRAS, for example, have previously been linked to aggressive growth in more than 90% of pancreatic cancers, the team explains.

The team artificially caused pancreatitis in mice by treating them with cerulein, a signaling protein fragment that damages pancreatic tissue. ATDC gene expression (i.e. activation) did not increase right after the damage was caused. Rather, it took a few days to get going, which the team says is consistent with the timeframe required for acinar cells to reprogram genetically into their ductal cell forebears. Mutant KRAS and other genetic abnormalities induced aggressive pancreatic cancer in 100% of the mice used in the study — if the ATDC gene was present and active.

However, none of the mice used in the study developed pancreatic cancer in the absence of an active ATDC gene. Further experimentation has shown that ATDC gene expression triggers beta-catenin, a cell-signaling protein that activates another gene, SOX9. Previous research has linked SOX9 to the development of ductal stem cells and to the aggressive growth seen in PDA. The present study supports this link, finding that cells lacking ATDC can’t become cancerous due to their inability to induce SOX9 expression.

In human tissue, the team reports based on a study of 12 human pancreatic tissue samples, ATDC expression seems to be more pronounced than that seen in mice. Its activation increased further during the transition of ADM into human pancreatic ductal adenocarcinoma. The findings could help serve as a base for developing new prevention and treatment strategies for pancreatic cancer, the team concludes.

The paper “ATDC induces an invasive switch in KRAS-induced pancreatic tumorigenesis” has been published in the journal Genes & Development.

The atomic model of an entire human gene. Credit: Los Alamos National Laboratory.

Scientists perform billion-atom simulation of a human gene

The atomic model of an entire human gene. Credit: Los Alamos National Laboratory.

The atomic model of an entire human gene. Credit: Los Alamos National Laboratory.

Researchers have simulated a billion atoms which make up an entire human gene for a split-second. This is the largest simulation of human DNA and an important milestone towards the ultimate goal of digitally reproducing the human genome. 

“It is important to understand DNA at this level of detail because we want to understand precisely how genes turn on and off,” said Karissa Sanbonmatsu, a structural biologist at Los Alamos. “Knowing how this happens could unlock the secrets to how many diseases occur.”

Sanbonmatsu and colleagues performed their study on the Los Alamos’ Trinity supercomputer, the sixth fastest in the world. But even for this behemoth, simulating the intricate complexities of DNA was a huge challenge that required all of its computing resources. The model is quite slow too, simulating just one nanosecond of molecular activity per day.

DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. This incredible molecule contains all the instructions an organism needs to develop, live, and reproduce. Its structure is so neatly compacted and precise that you could string together all the DNA in a human body to wrap around the earth 2.5 million times.

The reason why the blueprint for life is so compact has to do with the way the string-like molecule is wound up in a network of tiny spools. The various ways in which these spools wind and unwind turn genes on and off. In other words, when the DNA is more compacted, genes are turned off and when DNA expands, genes are turned on.

Researchers do not yet fully understand how all of this process pans out, which is why they’ve developed this atomistic model. Solving this mystery could one day lead to novel gene therapies and medical applications.

But before that happens, we need much faster computers. Modeling billions and billions of atoms all moving at the same time requires phenomenal resources. And, if we want to model an entire chromosome (or even the human genome), scientists will have to wait for the next generation of supercomputers, such as exascale computers, which will be many times faster than today’s machines.

Scientific reference: Jaewoon Jung et al. Scaling molecular dynamics beyond 100,000 processor cores for large‐scale biophysical simulations, Journal of Computational Chemistry (2019). DOI: 10.1002/jcc.25840.


The ‘forager gene’ of humans and fruit flies works in practically the same way

An international team of researchers reports that a gene humans and fruit flies share has a similar effect on their behavior. The same gene is found in many species across the world, likely acting in a similar way.


Image via Pixabay.

This might seem ludicrous, but there was a time in which humans couldn’t go to the grocery store to get food. In those dark times, we had to forage our way into a meal. New research shows that one gene with significant impact on foraging behavior in fruit flies (Drosophila melanogaster) has a similar effect on our own foraging strategies.

Will search for food

The team, which includes researchers from Canada, the U.K., and the U.S. has found that a gene known as PRKG1 — which is present in a wide range of species — can dictate whether individuals are “assessors” or “locomotors” when foraging for food.

The team worked with a group of college volunteers, who were asked to play a video game on a tablet. The object of this game was to find as many berries (which were hidden among plants) as possible. Each participant could navigate the environment at will and click on individual berries to pick them up. After playing the game, each volunteer was asked to give a tissue sample for DNA testing.

Some volunteers took a perimeter-first approach, the team reports — these were the “assessors” — while others dove right into the thick of it — these are the “locomotors”. Next, the team looked at the differences in the human equivalent of the PRKG1 — a nucleotide polymorphism genotype called rs13499 — among these participants, and compare them with those seen in fruit flies.

Prior research has shown that one variant of the PRKG1 gene pushes flies towards the “assessor” pattern of behavior, while another makes them “locomotors”. Upon entering an area, assessors are more likely to tour its perimeter first, then move inward. Locomotors, in contrast, make a beeline for the first fruits they see.

If you’re thinking ‘hey, those behaviors seem pretty similar,’ you’re spot on. The team reports finding the same gene variants responsible for instigating locomotor or assessor behavior in fruit flies in their college participants, having the same effect in both species. They further note that the search paths taken by the human volunteers and the sitter and rover fruit flies were nearly identical.

The findings suggest that this gene-induced preference in foraging patterns likely holds for other species as well. The team adds that their findings also suggest the patterns of behavior we employ when pursuing our goals can also be connected with these two gene variants.

The paper “Self-regulation and the foraging gene (PRKG1) in humans” has been published in the journal PNAS.

Foxtail grass.

Grasses steal neighbors’ genes to one-up other species

Grasses don’t play evolution by the rules, a new study reports. Instead of putting in the time to evolve beneficial genes, they just steal them from neighbors.

Foxtail grass.

Image via Pixabay.

New research at the Department of Animal and Plant Sciences at the University of Sheffield found that grasses engage in lateral gene transfer to acquire new, beneficial genes. The findings can help scientists reduce the risk of so-called “super-weeds” appearing — which form when wild plants take genes from GM (genetically-modified) crops to become resistant to herbicides.

Nice genes you got there

The findings suggest that wild grasses are basically genetically modifying themselves to gain a competitive advantage. This process stands in contrast to the theory of evolution as described by Charles Darwin, where natural selection affects which genes get passed from parent to offspring. It’s also, probably, a very lucrative deal for the grasses.

“Grasses are simply stealing genes and taking an evolutionary shortcut,” says lead author Dr Luke Dunning from the Department of Animal and Plant Sciences at the University of Sheffield.

“They are acting as a sponge, absorbing useful genetic information from their neighbours to out compete their relatives and survive in hostile habitats without putting in the millions of years it usually takes to evolve these adaptations.”

Grasses — including power-crops such as wheat, rice, or sugar cane — are some of the most economically and ecologically important plants on Earth. In a bid to understand their evolutionary journey, the team looked at the genome of Alloteropsis semialata, or black seed grass. This plant is spread quite widely across the planet, making a home in grasslands throughout Africa, Asia, and Australia.

Alloteropsis semialata flowers.

Alloteropsis semialata flowers.
Image credits Marjorie Lundgren via Wikimedia.

A. semialata’s genome was then compared to that of approximately 150 other species of grasses, including rice, maize, millets, barley, and bamboo. Based on this comparison, the team identified several genes that the grass laterally acquired from distant relatives (they looked for DNA sequences that were similar between two or more grass species). Furthermore, they found evidence that this process happens on a local level — in other words, the grass takes genes from its ecosystem-mates.

“We also collected samples of Alloteropsis semialata from tropical and subtropical places in Asia, Africa, and Australia so that we could track down when and where the transfers happened,” said Dr Dunning.

“Counterfeiting genes is giving the grasses huge advantages and helping them to adapt to their surrounding environment and survive — and this research also shows that it is not just restricted to Alloteropsis semialata as we detected it in a wide range of other grass species”

The team points out that this process is essentially the same as the technology behind GMO crops. As such, they hope the findings will help “us as a society reconsider how we view GM technology.”

“Eventually, this research may also help us to understand how genes can escape from GM crops to wild species or other non-GM crops, and provide solutions to reduce the likelihood of this happening,” Dr Dunning adds. “The next step is to understand the biological mechanism behind this phenomenon and we will carry out further studies to answer this.”

The paper “Lateral transfers of large DNA fragments spread functional genes among grasses” has been published in the journal Proceedings of the National Academy of Sciences.

Professor Harbans Bariana. Credit: University of Sydney.

Scientists harvest wild genes to give food crops an edge against diseases

Professor Harbans Bariana. Credit: University of Sydney.

Professor Harbans Bariana. Credit: University of Sydney.

Modern food crops have undergone substantial changes with respect to their wild counterparts, be they through traditional breeding techniques or gene editing. This is to optimize the crops’ agronomic traits, such as yield, but in doing so farmers are now growing plants with less genetic diversity — and this makes them very vulnerable to diseases. Seeking to address this gap, an international team of researchers has developed a revolutionary new technique that quickly and cheaply identifies genes associated with disease-fighting capabilities in wild crops. Ultimately, these genes could be added to the genomes of modern cousins in order to boost their resilience.

The technique called AgRenSeq combines high-throughput DNA sequencing and bioinformatics to create a functional library of disease resistant genes in wild crops. Using an algorithm that the team developed, researchers can perform a quick scan for relevant genes.

“We have found a way to scan the genome of a wild relative of a crop plant and pick out the resistance genes we need: and we can do it in record time. This used to be a process that took 10 or 15 years and was like searching for a needle in a haystack,” Dr. Brande Wulff, a crop genetics project leader at the John Innes Centre and a lead author of the study, said in a statement.

Once the genes are identified, researchers move to the lab where they can clone the genes and introduce them into various domestic crops. In a demonstration, the researchers led by Harbans Bariana, an expert in cereal rust genetics from the Sydney Institute of Agriculture, identified and then cloned four wild wheat genes that offer protection against stem rust pathogens. This all took a couple of months and cost only thousands of dollars instead of taking decades and millions of dollars. The same method could be used for soybeans, peas, cotton, maize, potatoes, barley, cocoa, and just about any food crop.

“What we have now is a library of disease resistance genes and we have developed an algorithm that enables researchers to quickly scan that library and find functional resistance genes,” said Dr Sanu Arora, the first author of the paper from the John Innes Centre.

Dr Wulff said: “This is the culmination of a dream, the result of many year’s work. Our results demonstrate that AgRenSeq is a robust protocol for rapidly discovering resistance genes from a genetically diverse panel of a wild crop relative,” he said.

“If we have an epidemic, we can go to our library and inoculate that pathogen across our diversity panel and pick out the resistance genes. Using speed cloning and speed breeding we could deliver resistance genes into elite varieties within a couple of years, like a phoenix rising from the ashes.”

The findings appeared in the journal Nature Biotechnology

Running man.

One broken gene made us very good runners

A genetic fluke two to three million years ago turned humans into the best endurance runners around.

Running man.

Image via Pixabay.

A new paper published by researchers from the University of California San Diego School of Medicine reports that our ancestors’ functional loss of one gene called CMAH dramatically shifted our species’ evolutionary path. The loss altered significant metabolic processes, with impacts on fertility rates and risk of developing cancer.

The same change may have also made humans one of the best long-distance runners on Earth, the team adds.

These genes were made for runnin’

Our ancestors were presumably quite busy two to three million years ago transitioning from living in trees to live on the savannah. They were able to walk upright by this time, but they weren’t particularly good at it.

However, soon after this, some of our ancestors’ physiology starts undergoing some striking changes. Most relevant are shifts we see in their skeletons, resulting in long legs, big feet, and large gluteal muscles (butts) — all very good for walking around. These shifts were also accompanied by the evolution of sweat glands with much the same layout and capacity as ours which, according to the team, is quite expansive and much better at dissipating heat than that of other large mammals.

In other words, humanity received powerful legs and one of the most solid cooling systems in one fell swoop.

Our ancestors proceeded to use their new toys to hunt and eat anything they could bring down. They did so by adopting a hunting pattern unique among primates (and very rare among animals in general) known as persistence hunting: they would go out in the heat of the day, when other carnivores were resting, relying on their legs and sweat glands to chase prey until — exhausted and overheated — it couldn’t physically run away anymore.

We didn’t know much about the biological changes that underpinned this radical change, however. The first clues were uncovered around 20 years ago — when Ajit Varki, a physician-scientist at the University of California, San Diego (UCSD), and colleagues unearthed one of the first genetic differences between humans and chimps: a gene called CMP-Neu5Ac Hydroxylase (CMAH). Other species of primates also have this gene.

We, however, have a broken version of CMAH. Varki’s team calculated that this genetic change happened 2 million to 3 million years ago, based on the genetic differences among primates and other animals.

More recent research has shown that mice models with a muscular dystrophy-like syndrome exhibit more acute symptoms when this gene is inactivated. This hinted to Varki that the faulty gene might be what led to the changes our ancestors experienced in the savannahs.

“Since the mice were also more prone to muscle dystrophy, I had a hunch that there was a connection to the increased long distance running and endurance of Homo,” said Varki.

UCSD graduate student Jonathan Okerblom, the study’s first author, put the theory to the test. He built mouse running wheels, borrowed a mouse treadmill, and pitted mice with a normal and broken version of CMAH to the task.

“We evaluated the exercise capacity (of mice lacking the CMAH gene), and noted an increased performance during treadmill testing and after 15 days of voluntary wheel running,” Okerblom explained.

The two then consulted Ellen Breen, Ph.D., a research scientist in the division of physiology, part of the Department of Medicine in the UC San Diego School of Medicine. She examined the mice’s leg muscles before and after running different distances, some after 2 weeks and some after 1 month.

After training, mice with the human-like version of CMAH ran 12% faster and 20% longer than the other mice, the team reports. Breen adds that the mice displayed greater resistance to fatigue, increased mitochondrial respiration and hind-limb muscle, with more capillaries to increase blood and oxygen supply. Taken together, Varki says the data suggest CMAH loss contributed to improved skeletal muscle capacity for oxygen utilization.

“And if the findings translate to humans, they may have provided early hominids with a selective advantage in their move from trees to becoming permanent hunter-gatherers on the open range.”

The most likely cause of this change was evolutionary pressures associated with an ancient pathogen, the team explains.

The version of the gene we carry determines the loss of a sialic acid called N-glycolylneuraminic acid (Neu5Gc), and accumulation of its precursor, called N-acetylneuraminic acid or Neu5Ac, which differs by only a single oxygen atom. Sialic acids serve as vital contact points for cell-to-cell interaction and cellular interactions with the surrounding environment. This change likely led to enhanced innate immunity in early hominids, according to past research.

Sialic acids may also be a biomarker for cancer risk, and the team has also reported that certain sialic acids are associated with increased risk of type 2 diabetes; may contribute to elevated cancer risk associated with red meat consumption, and trigger inflammation.

“They are a double-edged sword,” said Varki. “The consequence of a single lost gene and a small molecular change that appears to have profoundly altered human biology and abilities going back to our origins.”

The paper “Human-like Cmah inactivation in mice increases running endurance and decreases muscle fatigability: implications for human evolution” has been published in the journal Proceedings of the Royal Society B.

This fungus senses gravity using a gene it borrowed from bacteria

If you zoom in on it, the pin mold fungus Phycomyces blakesleeanus looks like a ghastly pine forest with its thin, elongated bodies reaching upwards. But how does the fungus know which way is up? According to a new study, it does so via a bacteria gene that it acquired and tweaked in order to create gravity-sensing crystals. 

Phycomyces fruiting bodies. Each stalk is a single cell that elongates to form a structure 1-3 cm tall, with a spore-containing sphere at its tip. The spores accumulate melanin as they mature, explaining the black color. Inset: An OCTIN crystal from Phycomyces blakesleeanus; the crystal is about 5 microns across, dwarfing typical bacteria (1-2 microns in length) from which the OCTIN gene is likely to have been acquired.

Most people would consider fungi pretty dull — after all, all they do is grow, spread their spores and then grow some more. However, fungi have much more going for them than it initially appears.

How do you know which way is up (bonus points if you’ve read or seen Ender’s Game)? For us, as humans, the question almost doesn’t make any sense. Without going too much into the biomechanics of how we sense which way is up and which way is down, suffice to say that all animals have at least some idea of up and down. But plants and fungi grow upwards, so they, too, have developed mechanisms that aid them.

Researchers have known for quite a while that the pin mold fungus has octahedral protein crystals that, when placed in fluid-filled chambers (vacuoles), detect gravity. However, it was unclear exactly when and how they developed this ability. In order to clear this up, biologists purified the crystals and identified a protein which they named OCTIN. They found clear evidence of something called horizontal gene transfer, meaning that the fungus borrowed the ability from bacteria.

Basically, genetic information can be transmitted either vertically (from parents to offspring) or horizontally. Horizontal gene transfer (HGT) occurs when DNA is transferred between unrelated individuals. It typically happens to acquire useful functions, such as resistance to environmental extremes and expanded metabolic capacity. However, in most cases, HGT tends to happen through enzymes that confer these traits, and the original and acquired functions tend to remain closely related to each other.

This time, that’s wasn’t the case.

“We were surprised that OCTIN-related genes are found in bacteria and that all the evidence pointed to horizontal gene transfer from bacteria into the ancestor of Phycomyces,” said the authors. “This was intriguing because estimates of sedimentation show that bacteria are too small to employ gravity sensing structures. This made it clear that we were looking at the emergence of an evolutionary novelty based on how the proteins assembled.”

It’s also remarkable that the fungal OCTIN crystals can dramatically swell and dissolve based on the biochemical environment, which forms or breaks bonds between proteins. This also happens in bacteria, but on a much smaller scale. The overall crystal size was also much larger in the fungus than in the bacteria.

The presence of the OCTIN protein is not the end of the story. Researchers took things one step further and tried to “convince” mammalian cells to make fungal OCTIN, but these cells did not form crystals. Dr. Gregory Jedd, who led the group at the Temasek Life Sciences Laboratory from the National University of Singapore, concluded:

“We are currently searching for these factors with the aim of reconstituting OCTIN crystal formation in the test tube. This will allow us to better understand and manipulate the assembly process and its products. High-order assemblies like those formed by OCTIN are not uncommon in nature. Identifying and studying these types of proteins will not only reveal mechanisms of adaptation and evolution, but can also lead to engineered smart protein assemblies with applications in areas such as drug delivery and immune system modulation.”

Journal Reference: Nguyen TA, Greig J, Khan A, Goh C, Jedd G (2018) Evolutionary novelty in gravity sensing through horizontal gene transfer and high-order protein assembly. PLoS Biol 16(4): e2004920. https://doi.org/10.1371/journal.pbio.2004920

Scientists discover why cockroaches are such good survivors

Researchers sequenced the American cockroach‘s genome for the first time, discovering what makes them such great survivors.

Periplaneta americana Via Flickr

The American cockroach, also known as Periplaneta americana, possesses widely expanded gene families related to taste and smell, detoxification and immunity, compared with other insects, found a team of researchers who published their discovery on March 20 in the journal Nature Communications.

“It makes total sense in the context of the lifestyle,” said Coby Schal, an entomologist at North Carolina State University who was part of a team that last month reported an analysis of the genome of the German cockroach (Blattella germanica). “Many of the gene families that expanded in the American cockroach were also expanded in the German cockroach”, Schal said.

That actually makes sense because both species are omnivorous scavengers that can thrive on altered food in extremely unsanitary environments — at least by human standards.

The American cockroach originally comes from Africa but was introduced to the Americas in the 1500s. Unlike the German cockroach, which is found almost exclusively in human dwellings, the American cockroach only tends to venture into the basements or bottom levels of buildings, according to Schal.

In China, the cockroach is often called “xiao qiang,” meaning “little mighty,” according to Sheng Li, an entomology professor at South China Normal University in Guangzhou and lead author of the paper. “It’s a tiny pest, but has very strong vitality,” he said.

The two species are remarkable survivors and their mysterious abilities appear to lie within their genes. In the new paper, professor Sheng Li and his team found that American cockroaches have the second-largest genome of any insect ever sequenced, right behind the migratory locust (Locusta migratoria). Curiously enough, 60% of the insect’s genome consists of repetitive segments. Gene families related to taste and smell were much larger than those of other bugs, and scientists counted 522 taste receptors in the roach. German cockroaches possess a similar number of taste receptors (545), Schal said.

“They need very elaborate smell and taste systems in order to avoid eating toxic stuff,” Schal added.

Source: Flickr

Interestingly, American cockroaches also have large gene families responsible for metabolization of toxic substances, including some chemicals found in insecticides — their ‘cousins’, the German cockroaches have them too. Schal said that both roaches evolved this way long before humans ruled the world. Resistance to toxic substances developed in roaches thanks to the abundance of toxin-producing bacteria in their environments and their tendency to eat rotten plant matter, he explained.

In addition, the American cockroach has a large number of immunity genes, perhaps another adaptation to unsanitary environments and fermenting food sources, Li and colleagues wrote.

Finally, the team discovered that the insect had a large number of genes devoted to physical development, such as genes responsible for synthesizing the insect’s juvenile hormone or the proteins in its exoskeleton. Authors were not surprised by this since American cockroaches can measure up to 2 inches (53 millimeters) long.

A greater understanding of the cockroach genome could help researchers come up with new ways to control theses pest species. One interesting research interest, Schal said, is the Asian cockroach (Blattella asahinai), a close relative of the pesky German cockroach that lives outdoors and doesn’t really bother humans. It would be interesting to see what are the differences between the Asian and German cockroach genomes.

Still, there’s a long way to go before we can see the broad picture of cockroach genetics.

“There are 5,000 described species of cockroaches, and now we have two [full] genomes,” Schal concluded. “So we need more.”

Gene mutation doesn’t make women diagnosed with breast cancer more likely to die

Angelina Jolie made headlines when she underwent preventative surgery after learning she had an up to 87% chance of developing breast cancer. Doctors had found that the star had mutations in BRCA genes which increase a woman’s risk of breast cancer by four-to-eightfold. Now, new findings suggest that Jolie may have been too rushed.

Credit: Wikimedia Commons.

Credit: Wikimedia Commons.

Scientists at the University of Southampton, UK, recently reported that women who carry a mutation in the BRCA1 or BRCA2 genes are not more likely to die after a breast cancer diagnosis than non-carriers. What’s more, carrying these mutations might, in fact, boost the odds of beating cancer if the diagnosis is triple-negative breast cancer.

BRCA mutations can cause cancer because the DNA self-repair mechanisms can malfunction. Besides breast cancer, these mutations have been linked to an increased risk of ovarian and prostate cancers.

“Women diagnosed with early breast cancer who carry a BRCA mutation are often offered double mastectomies soon after their diagnosis or chemotherapy treatment” compared to non-mutation carriers, study co-author Diana Eccles of the University of Southampton said in a statement.

“Our findings suggest that this surgery does not have to be immediately undertaken along with the other treatment.”

The study involved 2,733 British women aged 18-40 who had been diagnosed with breast cancer between 2000 and 2008. About 12 percent of the patients had a BRCA mutation, yet again confirming the association between this ‘faulty gene’ and breast cancer. Roughly 30 to 60 percent of BRCA1 or BRCA2 carriers will develop breast cancer in their lifetime, compared to an estimated 12 percent of women in the general population.

After the women’s medical records were tracked for up to ten years, researchers found that 651 of 678 total deaths were due to breast cancer. Most importantly, they uncovered that there was no difference in overall survival two, five, or ten years after diagnosis for women with and without a BRCA mutation. Actually, those with a BRCA mutation had slightly higher survival rates for the first two years after diagnosis, in the case of patients with triple-negative breast cancer.

About a third of those with the BRCA mutation had a double mastectomy to remove both breasts after being diagnosed with cancer, the same surgery Jolie went through. This surgery did not appear to improve their chances of survival at the 10-year mark, according to the findings published in The Lancet Oncology.

The findings might come as a welcomed breath of fresh air for many young women newly diagnosed with breast cancer, particularly those who are BRCA carriers. It means that they can take time to discuss whether radical breast surgery is the right choice for them as part of a longer-term risk-reducing strategy.

“So long as women are treated appropriately and are safe there is no crashing hurry … they need to be given the space to get as much information as they can and not feel like they need to do it all at once,” Fran Boyle, Professor of Medical Oncology at the University of Sydney told the SMH. 

“This important topic needs more prospective research as preventive surgical measures might have an effect on what might be a very long life after a diagnosis of breast cancer at a young age,” wrote Peter Fasching from the Friedrich-Alexander University Erlangen-Nuremberg, Germany.

Credit: Pixabay.

Gene mutation very common in a Amish community might extend lifespan by 10 years

A tight-knit Amish community in Indiana might hold the secret to longlasting life in their genes. Researchers found that members carrying a key gene mutation lived ten years longer on average than those who lacked the mutation. Some companies are already working on longevity drugs based on the study’s findings.

Credit: Pixabay.

Credit: Pixabay.

Modern health-care and nutrition have vastly improved the human lifespan. Figures published by the Centers for Disease Control and Prevention (CDC) show that babies born in the United States in 1900 had a life expectancy of 50 years. In comparison, Americans born in 2012 have a life expectancy of 78.8 years. In terms of gender, women generally live longer than men, with one in every ten girls born in 2012 expected to live for more than 100 years. All of this is absolutely remarkable progress, but aren’t we nearing a brick wall?

Many scientists researching longevity are now investigating genes with hope that they might find new ways to increase life expectancy at a similar pace to that of the last century. It’s no secret that some people age ‘better’ than others, being less exposed to health risks than their peers despite living in the same environment, eating the same food and so on. It logically follows that the reason must be related to their genes.

One of the main reasons why we biologically age has to do with telomeres — the end of DNA strands which are meant to protect chromosomes from deterioration, functioning like shoelace caps. Every time DNA replicates, the telomeres get a bit shorter leading to what scientists call senescence. As the telomeres get shorter and shorter, cells ramp up production of certain proteins. By measuring the concentration of these proteins, it’s fairly easy to assess the aging process in the body.

One such protein is called plasminogen activator inhibitor-1 or PAI-1 for short. Researchers at Northwestern University’s School of Medicine found that this protein could play a major role in human longevity after they sequenced the genomes of 177 members of the Berne Amish community in Indiana.

Douglas Vaughan, a cardiologist, along with colleagues, determined that 43 of these men and women had a nonfunctional copy of SERPINE1, which is the gene that encodes for PAI-1. The average lifespan of the Berne community is about 75 years — slightly lower than the national average — but those with the SERPINE1 mutation live to a median age of 85.

“This-loss-of-function mutation in SERPINE1 effectively lowers the production of the protein PAI-1 by 50 percent in the individuals that carry one copy of the mutation,” says Vaughan. “This likely has multifactorial effects that reduce the internal signals and factors that drive senescence in cells and tissues, which in turn slows the aging process.”

A lower PAI-1 protein count in their body seems to make individuals more resilient in the face of disease. According to Vaughan and colleagues, Amish with the SERPINE1 mutation had no signs of diabetes as opposed to 7 percent of the Amish individuals with the normal SERPINE1 gene. What’s more, those with the mutation also exhibited a better metabolism and lower-than-average levels of fasting insulin, according to the findings published in Science Advances.

Previously, Israeli researchers identified another gene mutation that extends lifespan, also by ten years, but only in men.

“The findings astonished us because of the consistency of the anti-aging benefits across multiple body systems,” Vaughan said in a statement. “That played out in them having a longer lifespan. Not only do they live longer, they live healthier. It’s a desirable form of longevity. It’s their ‘health span.’”

Since Amish communities are so isolated, it’s fairly easy for unique genes and mutation to become widespread among the population within just a few generations. Amazingly, almost every living Amish can trace their roots to one of 200 German-Swiss immigrants that came to American during the 18th and 19th centuries. The big downside is that the little genetic variance makes the Amish population particularly susceptible to high rates of genetic disorders like dwarfism or development delays. In the general population, however, the SERPINE1 mutation is very rare.

The good news is that some scientists think that you don’t have to be born with such a mutation to reap the longevity benefits. Since there aren’t any apparent negative effects related to PAI-I deficiency, it’s possible to use drugs to target this protein. Already, Japanese researchers Tohoku University are conducting an early phase clinical trial with an orally active PAI-1 blocker. A Japanese company called Renascience holds the patent for the drug which is currently being licensed to Eirion Therapeutics in the United States. There, the drug is marketed as a treatment for baldness since one of the mechanisms by which PAI-1 contributes to aging is by limiting cell mobility, which can be important in hair growth. Besides preventing baldness, the drug might also prolong our lifespan — but that’s something which we won’t discover until the last clinical trials are reported.

Schematic describing the CRISPR gene-editing technology used to investigate the key gene that determines butterfly wing patterns. Credit: The George Washington University

Biologists find genetic master switch for the butterfly’s wing color

From eery iridescence to perfect camouflage, butterfly wings are colored in all sorts of intricate patterns. Given their sheer diversity, scientists have always thought that a complex melange of genes code such decorative forms. It turns out, however, that playing around with just two genes is enough to determine the wing’s lines and colors.

modified CRISPR butterfly

The left-hand side shows unmodified wing pattern of Heliconius eratus demophoon butterfly. On the right-hand side, we can see the same butterfly whose WntA gene was knocked out of action. Credit: Smithsonian Tropical Research Institute.

The findings were reported this week in the Proceedings of the National Academy of Sciences journal by an international team of scientists led by Bob Reed, an evolutionary developmental biologist at Cornell University in Ithaca, New York.

The two complementary genes, WntA and optix, were identified after the team altered the genomes of several butterfly species with CRISPR–Cas9 — a powerful gene editing technique which allows scientists to cut and paste DNA sequences. The pair of genes represents ‘adaptive hotspots’ since these code physical changes in the butterfly wings that appear to be adaptations to their environment.

Schematic describing the CRISPR gene-editing technology used to investigate the key gene that determines butterfly wing patterns. Credit: The George Washington University

Schematic describing the CRISPR gene-editing technology used to investigate the key gene that determines butterfly wing patterns. Credit: The George Washington University

Paint-by-number genes

When the genes were switched on and off in various species, among them the famous but gravely endangered monarch butterfly (Danaus plexippus), interesting things happened. Turning off WntA caused the markings and patterns on the wings to fade or disappear altogether. In monarchs, for instance, the trademark dark wing contouring faded to gray.

“Imagine a paint-by-number image of a butterfly,” said Owen McMillan, staff scientist at STRI and co-author, in a press relase. “The instructions for coloring the wing are written in the genetic code. By deleting some of the instructions, we can infer which part says ‘paint the number two’s red’ or ‘paint the number one’s black. Of course, it is a lot more complicated than this because what is actually changing are networks of genes that have a cascading effect on pattern and color.”

While WntA seems to color boundaries and borders, optix acts like a paintbrush that fills in the blanks. For example, when the team switched off this gene in the butterfly gulf fritillary (Agraulis vanillae), their wings turned gray or black instead of the characteristic red and orange color patterns.

Surprisingly, when optix was turned off in the common buckeye (Junonia coenia), its wings became covered in spots of bright, iridescent blue. This signals that the gene is responsible for physical changes beyond pigmentation, since iridescence is determined by tiny microscopic structures on the wing’s scales. This suggests the optix gene “probably played a huge role in wing evolution”, Reed told Nature.

“The butterflies and moths, the Lepidoptera, are the third largest group of organisms known on the planet,” said Arnaud Martin, now Assistant Professor of Biology at George Washington University and corresponding author of the study.

“Once we identified the sets of genes regulated by a gene like WntA, we can look at the sequence of different butterflies in the family tree to see when and where these changes took place during the 60 million years of butterfly evolution.”

Such research serves to provide more insight into butterfly evolution. It’s likely that WntA and optix are part of a wider framework that allowed the insects to constantly morph their appearance according to the environment. One prime adaptation is mimicry, an unusual behavior where animals take on the appearance of another, usually for protection.

“For us who are studying butterflies, which are non-traditional organisms for a laboratory, CRISPR is opening a treasure chest of opportunities we haven’t had before,” Martin told Nature.

Exposure to BPA might reprogram the brains of turtles — affecting them genetically

It’s never pleasant to come into contact with a pollutant, but BPA might be even worse for the environment than we thought.

Painted turtle eggs were brought from a hatchery in Louisiana, candled to ensure embryo viability and then incubated at male-permissive temperatures in a bed of vermiculite. Those exposed to BPA developed deformities to testes that held female characteristics. Image credits: Roger Meissen, MU Bond Life Sciences CenterClose.

Bisphenol A (typically abbreviated BPA) is a common chemical used in a variety of consumer products, including food storage containers, water bottles and certain resins. It’s been in commercial use since the late 1950s. BPA exhibits estrogen mimicking, hormone-like properties that raise concern about its effects on the environment, and it also affects the growth, reproduction, and development in aquatic organisms, fish being the most vulnerable. Now, researchers have found yet another negative effect the chemical has on wildlife: it can really mess up the brains of turtles.

Turtles are often regarded as an “indicator species,” being indicative of the environmental health of the entire ecosystem. So if something’s wrong with turtles, it could be that similar things are happening to other species in the same habitat. Cheryl Rosenfeld, an investigator in the Bond Life Sciences Center, along with other researchers at the University of Missouri, Westminster College and the Saint Louis Zoo, set out to see how BPA (a common pollutant) affects the turtles. Startingly, researchers report that the chemical can have a severe effect on their brains and behavior, making male turtles act like females and vice versa.

“Painted turtles lack sex chromosomes, and their gender is primarily determined by the incubation temperature of the egg during development–cooler temperatures yield more males while warmer temperatures yield more females,” said Rosenfeld, who also is an associate professor of biomedical sciences in MU’s College of Veterinary Medicine. “Previously, our research team found that exposure to BPA might override the brain development of male turtles and could induce female type behaviors. Our goal for this research was to determine the genetic pathways that correlate to the behavioral changes we identified.”

Rosenfeld wanted to see exactly how BPA does this, and she found that it basically affects the turtles’ gene expression, altering their mitochondrial and ribosomal pathways. Since the mitochondria are the powerhouse of the cell and convert nutrients into useful energy, BPA can change a lot of things. For instance, increased energy production inside brain cells can affect cognitive flexibility and memory. However, we’re only beginning to understand how this type of substance can damage the environment because we don’t know that much about cellular mechanisms and gene expressions in creatures like turtles.

“Metabolic pathways are not well documented in turtles. We were able to use human metabolic models to infer pathway changes in turtles,” said Scott Givan, associate director of MU Informatics Research Core Facility and a co-author of the study. “After analyzing the genes, we were able to link gene expression changes to behavioral changes.”

This is the first study to find a correlation between pollution, gene expression patterns, and behavioral changes in turtles. Although this is a newly discovered mechanism, researchers were able to show that the effects last for at least a year, and they believe that the damage BPA does to the critters might even be permanent.

Journal Reference: Lindsey K. Manshack, Caroline M. Conard, Sara J. Bryan, Sharon L. Deem, Dawn K. Holliday, Nathan J. Bivens, Scott A. Givan, Cheryl S. Rosenfeld. Transcriptomic alterations in the brain of painted turtles ( Chrysemys picta ) developmentally exposed to bisphenol A or ethinyl estradiol. Physiological Genomics, 2017; 49 (4): 201 DOI: 10.1152/physiolgenomics.00103.2016

Researchers find 6,500 genes expressed differently in men and women

Men and women might be from the same species, but it sometimes doesn’t look like it. Aside from the obvious physical and psychological differences, there are also more subtle elements. For instance, the way in which we react to drugs and viral infections varies for the two sexes, and this could be a big problem. We’re treating similar health problems in the same way for both men and women but this might not be the wisest thing — which is why researchers are trying to chart out genetic differences. Now, Prof. Shmuel Pietrokovski and Dr. Moran Gershoni of the Weizmann Institute’s Molecular Genetics Department have created the most detailed map of these differences.

6500 genes are expressed differently in men and women. Image credits: Weizmann Institute of Science.

Pietrokovski and Gershoni started with a specific problem: about 15% of couples trying to conceive are defined as infertile, which is quite a lot. However, having a mutation that makes you infertile is the first thing that you’d expect evolution to weed out, because the mutation directly threatens the spread of the population. So why then are these mutations so common? The reason is, researchers argue, that these are sperm mutations which only affect men. A mutation that’s detrimental only to half of the population, no matter how damaging, can be freely passed on to the next generation.

They wanted to see all such genes which manifest differently and might be passed on in the same way, not only relating to fertility. They turned to the GTEx project — a very large study of human gene expression recorded for over 500 adults. They analyzed around 20,000 protein-coding genes, sorting them by sex and looking for differences. They found 6,500 genes which have a bias towards one sex or the other in at least one tissue. For instance, genes for hair growth on the skin were better represented in men (which was expected), while fat storage was also better expressed in women (also expected). But not everything was as evident.

For instance, some genes were only expressed in the left ventricle of the heart in women. Of those genes, one is also related to calcium uptake, so scientists believe it serves as an adaptive mechanism for the onset of menopause. Yet another gene that was mainly expressed in women was active in the brain, but its function is completely unknown.

Researchers also wanted to see to what extend damaging mutations are tolerated or weeded out, and this was pretty unclear. They did see that sexually-biased genes were less likely to be eliminated.

“The more a gene was specific to one sex, the less selection we saw on the gene. And one more difference: This selection was even weaker with men,” says Gershoni.

The best thing they have to serve as an explanation is a theory of sexual evolution proposed in the 1930s.

“In many species, females can produce only a limited number of offspring while males can, theoretically, father many more; so the species’ survival will depend on more viable females in the population than males,” explains Pietrokovski. “Thus natural selection can be more ‘lax’ with the genes that are only harmful to males.”

This is the best such map we have so far, but there is still plenty of room to advance our knowledge. We still don’t know exactly why these genes manifest the way they do, and more importantly — what effect they have. With the ascent of personalized medical treatment, studies like this will become more and more important in the future.

“The basic genome is nearly the same in all of us, but it is utilized differently across the body and among individuals,” says Gershoni. “Thus, when it comes to the differences between the sexes, we see that evolution often works on the level of gene expression.” Pietrokovski adds: “Paradoxically, sex-linked genes are those in which harmful mutations are more likely to be passed down, including those that impair fertility. From this vantage point, men and women undergo different selection pressures and, at least to some extent, human evolution should be viewed as co-evolution. But the study also emphasizes the need for a better understanding of the differences between men and women in the genes that cause disease or respond to treatments.”

Journal Reference: Moran Gershoni and Shmuel Pietrokovski — The landscape of sex-differential transcriptome and its consequent selection in human adultsDOI: 10.1186/s12915-017-0352-z

Researchers complete 30% of the synthetic yeast chromosome — synthetic life is just around the corner

An international research effort to construct the first fully synthetic yeast is well under way. The scientists have fully designed the fungus’ genome and have already built five of its final sixteen chromosomes — planning to have the rest completed by the end of the year.

Image credits Paul / Pixabay.

Yeast has to be humanity’s favorite fungus. Sure, other shrooms taste better in a saute or make for a much more entertaining way to spend some free time, but yeast has been by our side since times immemorial. Whenever we’ve needed something fermented, yeast had our back. Without it, there would be no alcohol, no bread, no fish sauce!

Since modern industries need to ferment more stuff much faster and into a more varied range of end products than ever before (think biofuels, insulin, antibiotics, THC), scientists have spent the last two decades sequencing yeast genome to produce different strains useful for all these products. That still leaves us limited by much of the yeast’s genome, however, which nature sadly didn’t design for industrial applications — but not for long.

Led by NYU Langone geneticist Jef Boeke, PhD, and a team of more than 200 authors, the Synthetic Yeast Project (Sc2.0) has designed a full genome for a functioning synthetic version of Baker’s yeast (S. cerevisiae). The latest issue of seven papers coming from the group shows that they’ve successfully constructed almost one third of this genome — 5 out of 16 chromosomes. They plan to have the rest ready by the end of the year. The new round of papers consists of an overview paper and five individual ones describing the first assembly of synthetic yeast chromosomes synII, synV, synVI, synX, and synXII. A seventh paper provides a first look at the 3D structures of synthetic chromosomes in the cell nucleus.

“This work sets the stage for completion of designer, synthetic genomes to address unmet needs in medicine and industry,” says Boeke, director of NYU Langone’s Institute for Systems Genetics.

“Beyond any one application, the papers confirm that newly created systems and software can answer basic questions about the nature of genetic machinery by reprogramming chromosomes in living cells.”

Learning the A’s and C’s

Apart from the immediate utility of having a tailorable yeast strain to apply in industry, Baker’s yeast was selected because of it’s relative simplicity and similarity to human cells. Sc2.0’s researchers are akin to a group of genetic programmers — they add or remove parts of DNA from chromosomes to dictate new function or prevent diseases or weakness to various factors. It makes sense to start with a simple ‘program’ until you learn the basics, which you can then apply to more complex systems.

Three years ago, Sc2.0 successfully assembled the first synthetic chromosome (chromosome 3 or synIII) out of 272,871 base pairs — the blocks which make up DNA. This process starts with the researchers screening libraries of yeast strains to find which genes are most likely to have useful features. Then, they planning thousands of permutations in the genome in a process somewhat similar to very rapid evolution. Some of these changes introduce the new genes to make the yeast exhibit desired features, others remove bits of DNA which were shown not to have a function in past trials.

Stained polytene chromosomes.
Image credits Doc. RNDr. Josef Reischig, CSc.

After the computer models are finished, the team starts assembling the edited DNA sequence bit by bit until they have the whole thing. The completed sequences are then introduced into yeast cells, which handle synthesizing and finish building the chromosomes — the latest round of papers describes a major innovation in this last step.

Until now, the researchers had to finish building once piece of a chromosome before work could begin on the latter, severely limiting their speed. These sequential requirements bottle-necked the process and increased cost, Boeke said. So the team made efforts to “parallelize” chromosome assembly, with different labs around the world synthesizing different bits in strains which were then mated. The resulting yeast strains would in some instances have even more than one fully synthetic chromosome. A paper led by Leslie Mitchell, PhD, a post-doctoral fellow from Boeke’s lab at NYU Langone, described the construction of a strain containing three synthetic chromosomes.

“Steps can be accomplished at the same time in many locales and then assembled at the end, like networking laptops to create a global super computer,” says Mitchell.

Another paper describes how a team at Tsinghua University used the same parallelized method to synthesize chromosome synXII, which formed a molecule with more than a million base pairs (one megabase) in length when fully assembled — the longest synthetic chromosome ever made by humans. It’s still only 1/3,000 the length of a human chromosome, but it’s closer than we’ve ever come before.

The researchers also found that they can edit some dramatic changes into the yeast genome without killing the cells. They survived even when the team moved whole sections of DNA from one chromosome to another, DNA swaps between yeast species, often with very little effects on the cells.

There’s a huge potential to synthetic yeast. Scientists could tailor their genome to produce anything we need from drugs, to food, new materials, almost anything — just from sugar and raw materials. It could fundamentally change how we think about a lot of industries, potentially churning the same products as factories and labs from a humble barrel.

But the work performed under the Sc2.0 project also revolutionizes how we know about genome building and synthetic life. Yeast is simple, but the end goal is to one day move on to tailor-made plants, maybe even to perfect the human genome. But we’re still a long way from that. Right now, the team will focus on getting their yeast’s final A’s, T’s, G’s, and C’s in place.


Scientists engineer mosquitoes that could stop malaria spread

A mosquito with a gene that blocks the malaria parasite has been created in the laboratory, a new study writes.

Image via Flickr.

Malaria is one of the most threatening diseases, with over 219 million cases identified in 2010 (and many other unreported); malaria is a mosquito-borne infectious disease, so if we want to fight it, eliminating mosquitoes seems like the way to go. But Tony James from the University of California, Irvine has a different approach in mind. He wants to modify mosquitoes so that they eliminate the parasite themselves.

They did this by using the CRISPR-Cas9 technology to create a ‘gene drive’ system that spreads an anti-malaria gene inside the mosquito population. The gene basically destroys malaria, and then spreads on to the next generations. Dr. Peter W. Atkinson, from the University of California, Riverside said:

“The study is extremely interesting since it demonstrates that gene drive mediated by the Cas9-based system can be achieved in this important pest species in the laboratory. Should it prove to be translatable to field studies and should the effector gene being used prove to significantly reduce the capacity of the mosquito to carry the malaria vector, then it is quite possible that this technology would become an important tool in the control of malaria. As such it would constitute a very, very significant advance in the field. Another advantage of the approach is that it is not eradicating the mosquito species which can open a niche which other mosquitoes could fill. Rather it is potentially replacing the existing genotype with one that has a greatly reduced ability to transmit the pathogen responsible for malaria. The authors are right to invoke the need to consult with regional communities and experts in the application of this technology and that it would form part of much larger insect pest management and malaria control strategies.”

It’s not the first time Cas9 has been used for this purpose. In 2014, two different teams worked on similar things (1 & 2), but this is the first time the method has been proven successfully and fully transmitted to mosquito offspring. Using this approach can be much more effective than trying to eradicate mosquitoes. Dr. Gregory Lanzaro, Professor, Department of Pathology, Microbiology and Immunology at the University of California, Davis explains:

“Concern that drug and insecticide resistance are eroding recent successes in managing malaria has drawn attention to alternative approaches, including the use of genetically modified mosquitoes. This new study by Tony James and colleagues marks a significant advance toward the development of this strategy. The major advance is the incorporation of an anti-Plasmodium effector gene, in fact two of them, in a construct that includes what appears to be an efficient genetic drive system, CRISPR-Cas9. This new drive system is a major improvement because it can be ‘loaded’ with a relatively large payload, a feature that has proven elusive before now.”

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Of course, many more tests need to be done before this method can be implemented in the field, but there are reasons to be optimistic. One problem is that if you want to implement it, you have to make sure that these anti-malaria mosquitoes are successful and create many offspring, so in a way, it becomes counter productive to eliminate mosquitoes and you have to let them suck a lot of blood and spread out. Needless to say, this can be a very dangerous approach.

Scientists figure out why snakes have such long bodies

It’s something kids (and even grownups) often ask – why are snakes so long? When we think of animals, they generally have a head, a body, and limbs, but snakes only have a head and a very long body, so what makes them so different? Researchers from Portugal believe they finally have the answer.

This beautiful snake is shaped as it is thanks to a specific gene. Image via Pixabay.

A research team led by Moisés Mallo from Instituto Gulbenkian de Ciência (IGC, Portugal) has uncovered the mechanisms controlling the tissues that form the trunk, including the skeleton and the spinal cord. Their experiments have shown that the key is a gene called Oct4 one of the essential regulators of stem cells. However, it’s interesting to note that several other vertebrates contain the same gene, without having a similar body structure.

“We had found that Oct4 is the switch that leads to trunk formation, still we couldn’t explain the different trunk length observed in vertebrates, particularly in snakes. Therefore, we tested if this switch was being turned on or off during different periods of embryonic development in snakes compared to mice.”

What they found was that the gene remains active much longer in snakes than it does in other animals. If the gene was switched off sooner, then the snakes wouldn’t grow so long.

“The formation of different body regions works as a strong-arm contest of genes. Genes involved in trunk formation need to start ceasing activity so that the genes involved in tail formation can start working. In the case of snakes, we observed that the Oct4 gene is kept active during a longer period of embryonic development, which explains why snakes have such a long trunk and a very short tail”, says Rita Aires, who was also involved in the study.

The team also found that the gene emerged sometime during their reptile evolution, based on its DNA location.

A snake embryo. Photo by Francisca Leal, University of Florida.

The development of the body structure is generally dictated by genetic activity, so this doesn’t really come as a surprise. However, finding the mechanism which ensures this growth could enable us to better understand the development of other creatures and in time, it could even provide some medical benefits. Researchers are especially interested in the regeneration of bones and the spinal cord.

“We identified a key factor that allows essentially unlimited growth of trunk structures, as long as it remains active. Now we will investigate if we can use the Oct4 gene and the DNA region that maintains its activity to expand the cells that make the spinal cord, trying to regenerate it in case of injury.”

“We identified a key factor that allows essentially unlimited growth of trunk structures, as long as it remains active. Now we will investigate if we can use the Oct4 gene and the DNA region that maintains its activity to expand the cells that make the spinal cord, trying to regenerate it in case of injury.”

Human limbs might have evolved from shark gills

A controversial idea has just received some significant backing, as a group of Cambridge researchers found evidence supporting human limbs evolving from shark gills.

Credit: J. Andrew Gillis

In 1878, German anatomist Karl Gegenbaur proposed an evolutionary link between the gills of cartilaginous fish (such as skates and sharks) and the limbs of vertebrates. The idea was popular for a short bit, but was then generally discarded due to the lack of supporting evidence in the fossil record. However, support may come in the form of a genetic study – specifically, something called the Sonic hedgehog gene.

“Chondrichthyans (sharks, skates, rays and holocephalans) possess paired appendages that project laterally from their gill arches, known as branchial rays. This led Carl Gegenbaur to propose that paired fins (and hence tetrapod limbs) originally evolved via transformation of gill arches,” the study writes.

The Sonic hedgehog gene makes sure all your limbs are in the right place and have the right size. It dictates how the limbs will grow, maintaining the right direction for the skeleton growth. In cartilaginous fish, the gills are protected by flaps of skin supported by arches of cartilage. Interestingly, the purpose of the Sonic hedgehog gene plays the same role for the fish, directing the growth of gills and cartilage. This could indicate that the gene’s function remained unchanged across millions of years of evolution. Writing in this week’s edition of the journal Development, MBL scientist Andrew Gillis and his colleagues support this idea:

“Gegenbaur looked at the way that these branchial rays connect to the gill arches and noticed that it looks very similar to the way that the fin and limb skeleton articulates with the shoulder. The branchial rays extend like a series of fingers down the side of a shark gill arch,” said Andrew Gillis, who led the research, in a statement. “The fact that the Sonic hedgehog gene performs the same two functions in the development of gill arches and branchial rays in skate embryos as it does in the development of limbs in mammal embryos may help explain how Gegenbaur arrived at his controversial theory on the origin of fins and limbs.”

In order to show that the gene works in the same way, they inhibited it at several stages of skate’s development. They found that when inhibited early in development, branchial rays grew on the wrong side of the cartilage arch. When inhibited later in development, the branchial rays grew on the correct side, but were fewer in number.

“Taken to the extreme, these experiments could be interpreted as evidence that limbs share a genetic programme with gill arches because fins and limbs evolved by transformation of a gill arch in an ancestral vertebrate, as proposed by Gegenbaur,” Gillis said.

“However, it could also be that these structures evolved separately, but re-used the same pre-existing genetic programme. Without fossil evidence this remains a bit of a mystery — there is a gap in the fossil record between species with no fins and then suddenly species with paired fins — so we can’t really be sure yet how paired appendages evolved.”

Of course, this is still a hotly debated claim. It doesn’t seem likely for this gene to develop separately, but the fossil evidence is still missing. Additional research is needed to fully compare the functions of the gene, but even if this is further confirmed, I doubt the theory will be widely accepted without fossil evidence. Unfortunately, this type of evidence can be difficult or impossible to find, so this will likely remain an open question for year to come. But the premise is there, and the prospect is certainly interesting.

Journal Reference: A shared role for sonic hedgehog signalling in patterning chondrichthyan gill arch appendages and tetrapod limbs

Activating a single gene could reverse colon cancer growth

A new study on mice shows great promise for treating colon cancer – a simple genetic tweak can turn colorectal cancer cells into healthy tissue in a matter of days.

Image via Wikipedia.

Anti-cancer strategies generally involve killing off tumor cells, but a group of US researchers have tried a different approach – they coaxed the cells to turn back into healthy ones by reactivating a single gene. Remarkably, in only 2 weeks, the cancer cells were gone – regaining their initial function. Six months later, there was still no sign of cancer.

“Treatment regimes for advanced colorectal cancer involve combination chemotherapies that are toxic and largely ineffective, yet have remained the backbone of therapy over the last decade,” says senior study author Scott Lowe of the Memorial Sloan Kettering Cancer Center.

The gene they reactivated is called denomatous polyposis coli (Apc), a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors. The protein made by the Apc gene plays a critical role in several cellular processes that determine whether a cell may develop into a tumor. Apc is turned off in 90% of all colorectal cancers, so researchers thought if they could turn it back up, they could eliminate cancer cells – and it worked. Furthermore, Lowe and his team managed to reactivate the gene without causing noticeable side effects.

“The concept of identifying tumor-specific driving mutations is a major focus of many laboratories around the world,” says author Lukas Dow of Weill Cornell Medical College.. “If we can define which types of mutations and changes are the critical events driving tumor growth, we will be better equipped to identify the most appropriate treatments for individual cancers.”

However, there’s a problem when it comes to implementing this treatment to humans: we can’t edit human genes the same way we edit mice genes. Researchers will have to find a way to have the same effect without actually turning on the gene.

“It is currently impractical to directly restore Apc function in patients with colorectal cancer, and past evidence suggests that completely blocking Wnt signaling would likely be severely toxic to normal intestinal cells,” said Lowe. “However, our findings suggest that small molecules aimed at modulating, but not blocking, the Wnt pathway might achieve similar effects to Apc reactivation. Further work will be critical to determine whether Wnt inhibition or similar approaches would provide long-term therapeutic value in the clinic.”

We’re still years away before this actually becomes a viable option for treatment, but there are reasons to be optimistic.

Journal Reference: Lukas E. Dow, Kevin P. O’Rourke, Janelle Simon, Darjus F. Tschaharganeh, Johan H. van Es, Hans Clevers, Scott W. Lowe. Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer. Cell, 2015; 161 (7): 1539 DOI: 10.1016/j.cell.2015.05.033