Tag Archives: genetics

Biosciences

Of Zebrafish and Men

Zebrafisch

A novel experiment in gene-editing shows how limbs of Earth’s land-dwelling creatures may have evolved from their fishy ancestors.

From University of Chicago:

One of the great transformations required for the descendants of fish to become creatures that could walk on land was the replacement of long, elegant fin rays by fingers and toes. In the Aug. 17, 2016 issue of Nature, scientists from the University of Chicago show that the same cells that make fin rays in fish play a central role in forming the fingers and toes of four-legged creatures.

After three years of painstaking experiments using novel gene-editing techniques and sensitive fate mapping to label and track developing cells in fish, the researchers describe how the small flexible bones found at the ends of fins are related to fingers and toes, which are more suitable for life on land.

“When I first saw these results you could have knocked me over with a feather,” said the study’s senior author, Neil Shubin, PhD, the Robert R. Bensley Distinguished Service Professor of Organismal Biology and Anatomy at the University of Chicago. Shubin is an authority on the transition from fins to limbs.

…

The team focused on Hox genes, which control the body plan of a growing embryo along the head-to-tail, or shoulder-to-fingertip, axis. Many of these genes are crucial for limb development.

They studied the development of cells, beginning, in some experiments, soon after fertilization, and followed them as they became part of an adult fin. Previous work has shown that when Hox genes, specifically those related to the wrists and digits of mice (HoxD and HoxA), were deleted, the mice did not develop those structures. When Nakamura deleted those same genes in zebrafish, the long fins rays were greatly reduced.

“What matters is not what happens when you knock out a single gene but when you do it in combination,” Nakamura explained. “That’s where the magic happens.”

The researchers also used a high-energy CT scanner to see the minute structures within the adult zebrafish fin. These can be invisible, even to most traditional microscopes. The scans revealed that fish lacking certain genes lost fin rays, but the small bones made of cartilage fin increased in number.

The authors suspect that the mutants that Nakamura made caused cells to stop migrating from the base of the fin to their usual position near the tip. This inability to migrate meant that there were fewer cells to make fin rays, leaving more cells at the fin base to produce cartilage elements.

Read more here. A female specimen of a zebrafish (Danio rerio) breed with fantails. Courtesy: Wikipedia / Azul.

BigBang, Biosciences

Human Bloatware

Most software engineers and IT people are familiar with the term “bloatware“. The word is usually applied to a software application that takes up so much disk space and/or memory that its functional benefits are greatly diminished or rendered useless. Operating systems such as Windows and OSX are often characterized as bloatware — a newer version always seems to require an ever-expanding need for extra disk space (and memory) to accommodate an expanding array of new (often trivial) features with marginal added benefit.

DNA_Structure

But it seems that humans did not invent such obesity through our technology. Rather, a new genetic analysis shows that humans (and other animals) actually consist of biological bloatware, through a process which began when molecules of DNA first assembled the genes of the earliest living organisms.

From ars technica:

Eukaryotes like us are more complex than prokaryotes. We have cells with lots of internal structures, larger genomes with more genes, and our genes are more complex. Since there seems to be no apparent evolutionary advantage to this complexity—evolutionary advantage being defined as fitness, not as things like consciousness or sex—evolutionary biologists have spent much time and energy puzzling over how it came to be.

In 2010, Nick Lane and William Martin suggested that because they don’t have mitochondria, prokaryotes just can’t generate enough energy to maintain large genomes. Thus it was the acquisition of mitochondria and their ability to generate cellular energy that allowed eukaryotic genomes to expand. And with the expansion came the many different types of genes that render us so complex and diverse.

Michael Lynch and Georgi Marinov are now proposing a counter offer. They analyzed the bioenergetic costs of a gene and concluded that there is in fact no energetic barrier to genetic complexity. Rather, eukaryotes can afford bigger genomes simply because they have bigger cells.

First they looked at the lifetime energetic requirements of a cell, defined as the number of times that cell hydrolyzes ATP into ADP, a reaction that powers most cellular processes. This energy requirement rose linearly and smoothly with cell size from bacteria to eukaryotes with no break between them, suggesting that complexity alone, independently of cell volume, requires no more energy.

Then they calculated the cumulative cost of a gene—how much energy it takes to replicate it once per cell cycle, how much energy it takes to transcribe it into mRNA, and how much energy it takes to then translate that mRNA transcript into a functional protein. Genes may provide selective advantages, but those must be sufficient to overcome and justify these energetic costs.

At the levels of replication (copying the DNA) and transcription (making an RNA copy), eukaryotic genes are more costly than prokaryotic genes because they’re bigger and require more processing. But even though these costs are higher, they take up proportionally less of the total energy budget of the cell. That’s because bigger cells take more energy to operate in general (as we saw just above), while things like copying DNA only happens once per cell division. Bigger cells help here, too, as they divide less often.

Read the entire article here.

BigBang

Syndrome X

DNA_Structure

The quest for immortality or even great longevity has probably led humans since they first became self-aware. Entire cultural movements and industries are founded on the desire to enhance and extend our lives. Genetic research, of course, may eventually unlock some or all of life and death’s mysteries. In the meantime, groups of dedicated scientists continue to look for for the foundation of aging with a view to understanding the process and eventually slowing (and perhaps stopping) it. Richard Walker is one of these singularly focused researchers.

From the BBC:

Richard Walker has been trying to conquer ageing since he was a 26-year-old free-loving hippie. It was the 1960s, an era marked by youth: Vietnam War protests, psychedelic drugs, sexual revolutions. The young Walker relished the culture of exultation, of joie de vivre, and yet was also acutely aware of its passing. He was haunted by the knowledge that ageing would eventually steal away his vitality – that with each passing day his body was slightly less robust, slightly more decayed. One evening he went for a drive in his convertible and vowed that by his 40th birthday, he would find a cure for ageing.

Walker became a scientist to understand why he was mortal. “Certainly it wasn’t due to original sin and punishment by God, as I was taught by nuns in catechism,” he says. “No, it was the result of a biological process, and therefore is controlled by a mechanism that we can understand.”

Scientists have published several hundred theories of ageing, and have tied it to a wide variety of biological processes. But no one yet understands how to integrate all of this disparate information.

Walker, now 74, believes that the key to ending ageing may lie in a rare disease that doesn’t even have a real name, “Syndrome X”. He has identified four girls with this condition, marked by what seems to be a permanent state of infancy, a dramatic developmental arrest. He suspects that the disease is caused by a glitch somewhere in the girls’ DNA. His quest for immortality depends on finding it.

It’s the end of another busy week and MaryMargret Williams is shuttling her brood home from school. She drives an enormous SUV, but her six children and their coats and bags and snacks manage to fill every inch. The three big kids are bouncing in the very back. Sophia, 10, with a mouth of new braces, is complaining about a boy-crazy friend. She sits next to Anthony, seven, and Aleena, five, who are glued to something on their mother’s iPhone. The three little kids squirm in three car seats across the middle row. Myah, two, is mining a cherry slushy, and Luke, one, is pawing a bag of fresh crickets bought for the family gecko.

Finally there’s Gabrielle, who’s the smallest child, and the second oldest, at nine years old. She has long, skinny legs and a long, skinny ponytail, both of which spill out over the edges of her car seat. While her siblings giggle and squeal, Gabby’s dusty-blue eyes roll up towards the ceiling. By the calendar, she’s almost an adolescent. But she has the buttery skin, tightly clenched fingers and hazy awareness of a newborn.

Back in 2004, when MaryMargret and her husband, John, went to the hospital to deliver Gabby, they had no idea anything was wrong. They knew from an ultrasound that she would have clubbed feet, but so had their other daughter, Sophia, who was otherwise healthy. And because MaryMargret was a week early, they knew Gabby would be small, but not abnormally so. “So it was such a shock to us when she was born,” MaryMargret says.

Gabby came out purple and limp. Doctors stabilised her in the neonatal intensive care unit and then began a battery of tests. Within days the Williamses knew their new baby had lost the genetic lottery. Her brain’s frontal lobe was smooth, lacking the folds and grooves that allow neurons to pack in tightly. Her optic nerve, which runs between the eyes and the brain, was atrophied, which would probably leave her blind. She had two heart defects. Her tiny fists couldn’t be pried open. She had a cleft palate and an abnormal swallowing reflex, which meant she had to be fed through a tube in her nose. “They started trying to prepare us that she probably wouldn’t come home with us,” John says. Their family priest came by to baptise her.

Day after day, MaryMargret and John shuttled between Gabby in the hospital and 13-month-old Sophia at home. The doctors tested for a few known genetic syndromes, but they all came back negative. Nobody had a clue what was in store for her. Her strong Catholic family put their faith in God. “MaryMargret just kept saying, ‘She’s coming home, she’s coming home’,” recalls her sister, Jennie Hansen. And after 40 days, she did.

Gabby cried a lot, loved to be held, and ate every three hours, just like any other newborn. But of course she wasn’t. Her arms would stiffen and fly up to her ears, in a pose that the family nicknamed her “Harley-Davidson”. At four months old she started having seizures. Most puzzling and problematic, she still wasn’t growing. John and MaryMargret took her to specialist after specialist: a cardiologist, a gastroenterologist, a geneticist, a neurologist, an ophthalmologist and an orthopaedist. “You almost get your hopes up a little – ’This is exciting! We’re going to the gastro doctor, and maybe he’ll have some answers’,” MaryMargret says. But the experts always said the same thing: nothing could be done.

The first few years with Gabby were stressful. When she was one and Sophia two, the Williamses drove from their home in Billings, Montana, to MaryMargret’s brother’s home outside of St Paul, Minnesota. For nearly all of those 850 miles, Gabby cried and screamed. This continued for months until doctors realised she had a run-of-the-mill bladder infection. Around the same period, she acquired a severe respiratory infection that left her struggling to breathe. John and MaryMargret tried to prepare Sophia for the worst, and even planned which readings and songs to use at Gabby’s funeral. But the tiny toddler toughed it out.

While Gabby’s hair and nails grew, her body wasn’t getting bigger. She was developing in subtle ways, but at her own pace. MaryMargret vividly remembers a day at work when she was pushing Gabby’s stroller down a hallway with skylights in the ceiling. She looked down at Gabby and was shocked to see her eyes reacting to the sunlight. “I thought, ‘Well, you’re seeing that light!’” MaryMargret says. Gabby wasn’t blind, after all.

Despite the hardships, the couple decided they wanted more children. In 2007 MaryMargret had Anthony, and the following year she had Aleena. By this time, the Williamses had stopped trudging to specialists, accepting that Gabby was never going to be fixed. “At some point we just decided,” John recalls, “it’s time to make our peace.”

Mortal questions

When Walker began his scientific career, he focused on the female reproductive system as a model of “pure ageing”: a woman’s ovaries, even in the absence of any disease, slowly but inevitably slide into the throes of menopause. His studies investigated how food, light, hormones and brain chemicals influence fertility in rats. But academic science is slow. He hadn’t cured ageing by his 40th birthday, nor by his 50th or 60th. His life’s work was tangential, at best, to answering the question of why we’re mortal, and he wasn’t happy about it. He was running out of time.

So he went back to the drawing board. As he describes in his book, Why We Age, Walker began a series of thought experiments to reflect on what was known and not known about ageing.

Ageing is usually defined as the slow accumulation of damage in our cells, organs and tissues, ultimately causing the physical transformations that we all recognise in elderly people. Jaws shrink and gums recede. Skin slacks. Bones brittle, cartilage thins and joints swell. Arteries stiffen and clog. Hair greys. Vision dims. Memory fades. The notion that ageing is a natural, inevitable part of life is so fixed in our culture that we rarely question it. But biologists have been questioning it for a long time.

It’s a harsh world out there, and even young cells are vulnerable. It’s like buying a new car: the engine runs perfectly but is still at risk of getting smashed on the highway. Our young cells survive only because they have a slew of trusty mechanics on call. Take DNA, which provides the all-important instructions for making proteins. Every time a cell divides, it makes a near-perfect copy of its three-billion-letter code. Copying mistakes happen frequently along the way, but we have specialised repair enzymes to fix them, like an automatic spellcheck. Proteins, too, are ever vulnerable. If it gets too hot, they twist into deviant shapes that keep them from working. But here again, we have a fixer: so-called ‘heat shock proteins’ that rush to the aid of their misfolded brethren. Our bodies are also regularly exposed to environmental poisons, such as the reactive and unstable ‘free radical’ molecules that come from the oxidisation of the air we breathe. Happily, our tissues are stocked with antioxidants and vitamins that neutralise this chemical damage. Time and time again, our cellular mechanics come to the rescue.

Which leads to the biologists’ longstanding conundrum: if our bodies are so well tuned, why, then, does everything eventually go to hell?

One theory is that it all boils down to the pressures of evolution. Humans reproduce early in life, well before ageing rears its ugly head. All of the repair mechanisms that are important in youth – the DNA editors, the heat shock proteins, the antioxidants – help the young survive until reproduction, and are therefore passed down to future generations. But problems that show up after we’re done reproducing cannot be weeded out by evolution. Hence, ageing.

Most scientists say that ageing is not caused by any one culprit but by the breakdown of many systems at once. Our sturdy DNA mechanics become less effective with age, meaning that our genetic code sees a gradual increase in mutations. Telomeres, the sequences of DNA that act as protective caps on the ends of our chromosomes, get shorter every year. Epigenetic messages, which help turn genes on and off, get corrupted with time. Heat shock proteins run down, leading to tangled protein clumps that muck up the smooth workings of a cell. Faced with all of this damage, our cells try to adjust by changing the way they metabolise nutrients and store energy. To ward off cancer, they even know how to shut themselves down. But eventually cells stop dividing and stop communicating with each other, triggering the decline we see from the outside.

Scientists trying to slow the ageing process tend to focus on one of these interconnected pathways at a time. Some researchers have shown, for example, that mice on restricted-calorie diets live longer than normal. Other labs have reported that giving mice rapamycin, a drug that targets an important cell-growth pathway, boosts their lifespan. Still other groups are investigating substances that restore telomeres, DNA repair enzymes and heat shock proteins.

During his thought experiments, Walker wondered whether all of these scientists were fixating on the wrong thing. What if all of these various types of cellular damages were the consequences of ageing, but not the root cause of it? He came up with an alternative theory: that ageing is the unavoidable fallout of our development.

The idea sat on the back burner of Walker’s mind until the evening of 23 October 2005. He was working in his home office when his wife called out to him to join her in the family room. She knew he would want to see what was on TV: an episode of Dateline about a young girl who seemed to be “frozen in time”. Walker watched the show and couldn’t believe what he was seeing. Brooke Greenberg was 12 years old, but just 13 pounds (6kg) and 27 inches (69cm) long. Her doctors had never seen anything like her condition, and suspected the cause was a random genetic mutation. “She literally is the Fountain of Youth,” her father, Howard Greenberg, said.

Walker was immediately intrigued. He had heard of other genetic diseases, such as progeria and Werner syndrome, which cause premature ageing in children and adults respectively. But this girl seemed to be different. She had a genetic disease that stopped her development and with it, Walker suspected, the ageing process. Brooke Greenberg, in other words, could help him test his theory.

Uneven growth

Brooke was born a few weeks premature, with many birth defects. Her paediatrician labeled her with Syndrome X, not knowing what else to call it.

After watching the show, Walker tracked down Howard Greenberg’s address. Two weeks went by before Walker heard back, and after much discussion he was allowed to test Brooke. He was sent Brooke’s medical records as well as blood samples for genetic testing. In 2009, his team published a brief report describing her case.

Walker’s analysis found that Brooke’s organs and tissues were developing at different rates. Her mental age, according to standardised tests, was between one and eight months. Her teeth appeared to be eight years old; her bones, 10 years. She had lost all of her baby fat, and her hair and nails grew normally, but she had not reached puberty. Her telomeres were considerably shorter than those of healthy teenagers, suggesting that her cells were ageing at an accelerated rate.

All of this was evidence of what Walker dubbed “developmental disorganisation”. Brooke’s body seemed to be developing not as a coordinated unit, he wrote, but rather as a collection of individual, out-of-sync parts. “She is not simply ‘frozen in time’,” Walker wrote. “Her development is continuing, albeit in a disorganised fashion.”

The big question remained: why was Brooke developmentally disorganised? It wasn’t nutritional and it wasn’t hormonal. The answer had to be in her genes. Walker suspected that she carried a glitch in a gene (or a set of genes, or some kind of complex genetic programme) that directed healthy development. There must be some mechanism, after all, that allows us to develop from a single cell to a system of trillions of cells. This genetic programme, Walker reasoned, would have two main functions: it would initiate and drive dramatic changes throughout the organism, and it would also coordinate these changes into a cohesive unit.

Ageing, he thought, comes about because this developmental programme, this constant change, never turns off. From birth until puberty, change is crucial: we need it to grow and mature. After we’ve matured, however, our adult bodies don’t need change, but rather maintenance. “If you’ve built the perfect house, you would want to stop adding bricks at a certain point,” Walker says. “When you’ve built a perfect body, you’d want to stop screwing around with it. But that’s not how evolution works.” Because natural selection cannot influence traits that show up after we have passed on our genes, we never evolved a “stop switch” for development, Walker says. So we keep adding bricks to the house. At first this doesn’t cause much damage – a sagging roof here, a broken window there. But eventually the foundation can’t sustain the additions, and the house topples. This, Walker says, is ageing.

Brooke was special because she seemed to have been born with a stop switch. But finding the genetic culprit turned out to be difficult. Walker would need to sequence Brooke’s entire genome, letter by letter.

That never happened. Much to Walker’s chagrin, Howard Greenberg abruptly severed their relationship. The Greenbergs have not publicly explained why they ended their collaboration with Walker, and declined to comment for this article.

Second chance

In August 2009, MaryMargret Williams saw a photo of Brooke on the cover of People magazine, just below the headline “Heartbreaking mystery: The 16-year-old baby”. She thought Brooke sounded a lot like Gabby, so contacted Walker.

After reviewing Gabby’s details, Walker filled her in on his theory. Testing Gabby’s genes, he said, could help him in his mission to end age-related disease – and maybe even ageing itself.

This didn’t sit well with the Williamses. John, who works for the Montana Department of Corrections, often interacts with people facing the reality of our finite time on Earth. “If you’re spending the rest of your life in prison, you know, it makes you think about the mortality of life,” he says. What’s important is not how long you live, but rather what you do with the life you’re given. MaryMargret feels the same way. For years she has worked in a local dermatology office. She knows all too well the cultural pressures to stay young, and wishes more people would embrace the inevitability of getting older. “You get wrinkles, you get old, that’s part of the process,” she says.

But Walker’s research also had its upside. First and foremost, it could reveal whether the other Williams children were at risk of passing on Gabby’s condition.

For several months, John and MaryMargret hashed out the pros and cons. They were under no illusion that the fruits of Walker’s research would change Gabby’s condition, nor would they want it to. But they did want to know why. “What happened, genetically, to make her who she is?” John says. And more importantly: “Is there a bigger meaning for it?”

John and MaryMargret firmly believe that God gave them Gabby for a reason. Walker’s research offered them a comforting one: to help treat Alzheimer’s and other age-related diseases. “Is there a small piece that Gabby could present to help people solve these awful diseases?” John asks. “Thinking about it, it’s like, no, that’s for other people, that’s not for us.” But then he thinks back to the day Gabby was born. “I was in that delivery room, thinking the same thing – this happens to other people, not us.”

Still not entirely certain, the Williamses went ahead with the research.

Amassing evidence

Walker published his theory in 2011, but he’s only the latest of many researchers to think along the same lines. “Theories relating developmental processes to ageing have been around for a very long time, but have been somewhat under the radar for most researchers,” says Joao Pedro de Magalhaes, a biologist at the University of Liverpool. In 1932, for example, English zoologist George Parker Bidder suggested that mammals have some kind of biological “regulator” that stops growth after the animal reaches a specific size. Ageing, Bidder thought, was the continued action of this regulator after growth was done.

Subsequent studies showed that Bidder wasn’t quite right; there are lots of marine organisms, for example, that never stop growing but age anyway. Still, his fundamental idea of a developmental programme leading to ageing has persisted.

For several years, Stuart Kim’s group at Stanford University has been comparing which genes are expressed in young and old nematode worms. It turns out that some genes involved in ageing also help drive development in youth.

Kim suggested that the root cause of ageing is the “drift”, or mistiming, of developmental pathways during the ageing process, rather than an accumulation of cellular damage.

Other groups have since found similar patterns in mice and primates. One study, for example, found that many genes turned on in the brains of old monkeys and humans are the same as those expressed in young brains, suggesting that ageing and development are controlled by some of the same gene networks.

Perhaps most provocative of all, some studies of worms have shown that shutting down essential development genes in adults significantly prolongs life. “We’ve found quite a lot of genes in which this happened – several dozen,” de Magalhaes says.

Nobody knows whether the same sort of developmental-programme genes exist in people. But say that they do exist. If someone was born with a mutation that completely destroyed this programme, Walker reasoned, that person would undoubtedly die. But if a mutation only partially destroyed it, it might lead to a condition like what he saw in Brooke Greenberg or Gabby Williams. So if Walker could identify the genetic cause of Syndrome X, then he might also have a driver of the ageing process in the rest of us.

And if he found that, then could it lead to treatments that slow – or even end – ageing? “There’s no doubt about it,” he says.

Public stage

After agreeing to participate in Walker’s research, the Williamses, just like the Greenbergs before them, became famous. In January 2011, when Gabby was six, the television channel TLC featured her on a one-hour documentary. The Williams family also appeared on Japanese television and in dozens of newspaper and magazine articles.

Other than becoming a local celebrity, though, Gabby’s everyday life hasn’t changed much since getting involved in Walker’s research. She spends her days surrounded by her large family. She’ll usually lie on the floor, or in one of several cushions designed to keep her spine from twisting into a C shape. She makes noises that would make an outsider worry: grunting, gasping for air, grinding her teeth. Her siblings think nothing of it. They play boisterously in the same room, somehow always careful not to crash into her. Once a week, a teacher comes to the house to work with Gabby. She uses sounds and shapes on an iPad to try to teach cause and effect. When Gabby turned nine, last October, the family made her a birthday cake and had a party, just as they always do. Most of her gifts were blankets, stuffed animals and clothes, just as they are every year. Her aunt Jennie gave her make-up.

Walker teamed up with geneticists at Duke University and screened the genomes of Gabby, John and MaryMargret. This test looked at the exome, the 2% of the genome that codes for proteins. From this comparison, the researchers could tell that Gabby did not inherit any exome mutations from her parents – meaning that it wasn’t likely that her siblings would be able to pass on the condition to their kids. “It was a huge relief – huge,” MaryMargret says.

Still, the exome screening didn’t give any clues as to what was behind Gabby’s disease. Gabby carries several mutations in her exome, but none in a gene that would make sense of her condition. All of us have mutations littering our genomes. So it’s impossible to know, in any single individual, whether a particular mutation is harmful or benign – unless you can compare two people with the same condition.

All girls

Luckily for him, Walker’s continued presence in the media has led him to two other young girls who he believes have the same syndrome. One of them, Mackenzee Wittke, of Alberta, Canada, is now five years old, with has long and skinny limbs, just like Gabby. “We have basically been stuck in a time warp,” says her mother, Kim Wittke. The fact that all of these possible Syndrome X cases are girls is intriguing – it could mean that the crucial mutation is on their X chromosome. Or it could just be a coincidence.

Walker is working with a commercial outfit in California to compare all three girls’ entire genome sequences – the exome plus the other 98% of DNA code, which is thought to be responsible for regulating the expression of protein-coding genes.

For his theory, Walker says, “this is do or die – we’re going to do every single bit of DNA in these girls. If we find a mutation that’s common to them all, that would be very exciting.”

But that seems like a very big if.

Most researchers agree that finding out the genes behind Syndrome X is a worthwhile scientific endeavour, as these genes will no doubt be relevant to our understanding of development. They’re far less convinced, though, that the girls’ condition has anything to do with ageing. “It’s a tenuous interpretation to think that this is going to be relevant to ageing,” says David Gems, a geneticist at University College London. It’s not likely that these girls will even make it to adulthood, he says, let alone old age.

It’s also not at all clear that these girls have the same condition. Even if they do, and even if Walker and his collaborators discover the genetic cause, there would still be a steep hill to climb. The researchers would need to silence the same gene or genes in laboratory mice, which typically have a lifespan of two or three years. “If that animal lives to be 10, then we’ll know we’re on the right track,” Walker says. Then they’d have to find a way to achieve the same genetic silencing in people, whether with a drug or some kind of gene therapy. And then they’d have to begin long and expensive clinical trials to make sure that the treatment was safe and effective. Science is often too slow, and life too fast.

End of life

On 24 October 2013, Brooke passed away. She was 20 years old. MaryMargret heard about it when a friend called after reading it in a magazine. The news hit her hard. “Even though we’ve never met the family, they’ve just been such a part of our world,” she says.

MaryMargret doesn’t see Brooke as a template for Gabby – it’s not as if she now believes that she only has 11 years left with her daughter. But she can empathise with the pain the Greenbergs must be feeling. “It just makes me feel so sad for them, knowing that there’s a lot that goes into a child like that,” she says. “You’re prepared for them to die, but when it finally happens, you can just imagine the hurt.”

Today Gabby is doing well. MaryMargret and John are no longer planning her funeral. Instead, they’re beginning to think about what would happen if Gabby outlives them. (Sophia has offered to take care of her sister.) John turned 50 this year, and MaryMargret will be 41. If there were a pill to end ageing, they say they’d have no interest in it. Quite the contrary: they look forward to getting older, because it means experiencing the new joys, new pains and new ways to grow that come along with that stage of life.

Richard Walker, of course, has a fundamentally different view of growing old. When asked why he’s so tormented by it, he says it stems from childhood, when he watched his grandparents physically and psychologically deteriorate. “There was nothing charming to me about sedentary old people, rocking chairs, hot houses with Victorian trappings,” he says. At his grandparents’ funerals, he couldn’t help but notice that they didn’t look much different in death than they did at the end of life. And that was heartbreaking. “To say I love life is an understatement,” he says. “Life is the most beautiful and magic of all things.”

If his hypothesis is correct – who knows? – it might one day help prevent disease and modestly extend life for millions of people. Walker is all too aware, though, that it would come too late for him. As he writes in his book: “I feel a bit like Moses who, after wandering in the desert for most years of his life, was allowed to gaze upon the Promised Land but not granted entrance into it.”

 Read the entire story here.

Story courtesy of BBC and Mosaic under Creative Commons License.

Image: DNA structure. Courtesy of Wikipedia.

BigBang

Good Mutations and Breathing

Van_andel_113

Stem cells — the factories that manufacture all our component body parts — may hold a key to divining why our bodies gradually break down as we age. A new body of research shows how the body’s population of blood stem cells mutates, and gradually dies, over a typical lifespan. Sometimes these mutations turn cancerous, sometimes not. Luckily for us, the research is centered on the blood samples of Hendrikje van Andel-Schipper — she died in 2005 at the age of 115, and donated her body to science. Her body showed a remarkable resilience — no hardening of the arteries and no deterioration of her brain tissue.  When quizzed about the secret of her longevity, she once retorted, “breathing”.

From the New Scientist:

Death is the one certainty in life – a pioneering analysis of blood from one of the world’s oldest and healthiest women has given clues to why it happens.

Born in 1890, Hendrikje van Andel-Schipper was at one point the oldest woman in the world. She was also remarkable for her health, with crystal-clear cognition until she was close to death, and a blood circulatory system free of disease. When she died in 2005, she bequeathed her body to science, with the full support of her living relatives that any outcomes of scientific analysis – as well as her name – be made public.

Researchers have now examined her blood and other tissues to see how they were affected by age.

What they found suggests, as we could perhaps expect, that our lifespan might ultimately be limited by the capacity for stem cells to keep replenishing tissues day in day out. Once the stem cells reach a state of exhaustion that imposes a limit on their own lifespan, they themselves gradually die out and steadily diminish the body’s capacity to keep regenerating vital tissues and cells, such as blood.

Two little cells

In van Andel-Schipper’s case, it seemed that in the twilight of her life, about two-thirds of the white blood cells remaining in her body at death originated from just two stem cells, implying that most or all of the blood stem cells she started life with had already burned out and died.

“Is there a limit to the number of stem cell divisions, and does that imply that there’s a limit to human life?” asks Henne Holstege of the VU University Medical Center in Amsterdam, the Netherlands, who headed the research team. “Or can you get round that by replenishment with cells saved from earlier in your life?” she says.

The other evidence for the stem cell fatigue came from observations that van Andel-Schipper’s white blood cells had drastically worn-down telomeres – the protective tips on chromosomes that burn down like wicks each time a cell divides. On average, the telomeres on the white blood cells were 17 times shorter than those on brain cells, which hardly replicate at all throughout life.

The team could establish the number of white blood cell-generating stem cells by studying the pattern of mutations found within the blood cells. The pattern was so similar in all cells that the researchers could conclude that they all came from one of two closely related “mother” stem cells.

Point of exhaustion

“It’s estimated that we’re born with around 20,000 blood stem cells, and at any one time, around 1000 are simultaneously active to replenish blood,” says Holstege. During life, the number of active stem cells shrinks, she says, and their telomeres shorten to the point at which they die – a point called stem-cell exhaustion.

Holstege says the other remarkable finding was that the mutations within the blood cells were harmless – all resulted from mistaken replication of DNA during van Andel-Schipper’s life as the “mother” blood stem cells multiplied to provide clones from which blood was repeatedly replenished.

She says this is the first time patterns of lifetime “somatic” mutations have been studied in such an old and such a healthy person. The absence of mutations posing dangers of disease and cancer suggest that van Andel-Schipper had a superior system for repairing or aborting cells with dangerous mutations.

Read the entire article here.

Image: Hendrikje van Andel-Schipper, aged 113. Courtesy of Wikipedia.

BigBang

Chromosomal Chronometer

Researchers find possible evidence of DNA mechanism that keep track of age. It is too early to tell if changes over time in specific elements of our chromosomes result in or are a consequence of aging. Yet, this is a tantalizing discovery that bodes well for a better understanding into the genetic and biological systems that underlie the aging process.

From the Guardian:

A US scientist has discovered an internal body clock based on DNA that measures the biological age of our tissues and organs.

The clock shows that while many healthy tissues age at the same rate as the body as a whole, some of them age much faster or slower. The age of diseased organs varied hugely, with some many tens of years “older” than healthy tissue in the same person, according to the clock.

Researchers say that unravelling the mechanisms behind the clock will help them understand the ageing process and hopefully lead to drugs and other interventions that slow it down.

Therapies that counteract natural ageing are attracting huge interest from scientists because they target the single most important risk factor for scores of incurable diseases that strike in old age.

“Ultimately, it would be very exciting to develop therapy interventions to reset the clock and hopefully keep us young,” said Steve Horvath, professor of genetics and biostatistics at the University of California in Los Angeles.

Horvath looked at the DNA of nearly 8,000 samples of 51 different healthy and cancerous cells and tissues. Specifically, he looked at how methylation, a natural process that chemically modifies DNA, varied with age.

Horvath found that the methylation of 353 DNA markers varied consistently with age and could be used as a biological clock. The clock ticked fastest in the years up to around age 20, then slowed down to a steadier rate. Whether the DNA changes cause ageing or are caused by ageing is an unknown that scientists are now keen to work out.

“Does this relate to something that keeps track of age, or is a consequence of age? I really don’t know,” Horvath told the Guardian. “The development of grey hair is a marker of ageing, but nobody would say it causes ageing,” he said.

The clock has already revealed some intriguing results. Tests on healthy heart tissue showed that its biological age – how worn out it appears to be – was around nine years younger than expected. Female breast tissue aged faster than the rest of the body, on average appearing two years older.

Diseased tissues also aged at different rates, with cancers speeding up the clock by an average of 36 years. Some brain cancer tissues taken from children had a biological age of more than 80 years.

“Female breast tissue, even healthy tissue, seems to be older than other tissues of the human body. That’s interesting in the light that breast cancer is the most common cancer in women. Also, age is one of the primary risk factors of cancer, so these types of results could explain why cancer of the breast is so common,” Horvath said.

Healthy tissue surrounding a breast tumour was on average 12 years older than the rest of the woman’s body, the scientist’s tests revealed.

Writing in the journal Genome Biology, Horvath showed that the biological clock was reset to zero when cells plucked from an adult were reprogrammed back to a stem-cell-like state. The process for converting adult cells into stem cells, which can grow into any tissue in the body, won the Nobel prize in 2012 for Sir John Gurdon at Cambridge University and Shinya Yamanaka at Kyoto University.

“It provides a proof of concept that one can reset the clock,” said Horvath. The scientist now wants to run tests to see how neurodegenerative and infectious diseases affect, or are affected by, the biological clock.

Read the entire article here.

Image: Artist rendition of DNA fragment. Courtesy of Zoonar GmbH/Alamy.

Technica

Britain’s Genomics NHS

The United Kingdom is plotting a visionary strategy that will put its treasured National Health Service (NHS) at the heart of the new revolution in genomics-based medical care.

From Technology Review:

By sequencing the genomes of 100,000 patients and integrating the resulting data into medical care, the U.K. could become the first country to introduce genome sequencing into its mainstream health system. The U.K. government hopes that the investment will improve patient outcomes while also building a genomic medicine industry. But the project will test the practical challenges of integrating and safeguarding genomic data within an expansive health service.

Officials breathed life into the ambitious sequencing project in June when they announced the formation of Genomics England, a company set up to execute the £100 million project. The goal is to “transform how the NHS uses genomic medicine,” says the company’s chief scientist, Mark Caulfield.

Those changes will take many shapes. First, by providing whole-genome sequencing and analysis for National Health Service patients with rare diseases, Genomics England could help families understand the origin of these conditions and help doctors better treat them. Second, the company will sequence the genomes of cancer patients and their tumors, which could help doctors identify the best drugs to treat the disease. Finally, say leaders of the 100,000 genomes project, the efforts could uncover the basis for bacterial and viral resistance to medicines.

“We hope that the legacy at the end of 2017, when we conclude the 100,000 whole-genome sequences, will be a transformed capacity and capability in the NHS to use this data,” says Caulfield.

In the last few years, the cost and time required to sequence DNA have plummeted (see “Bases to Bytes”), making the technology more feasible to use as part of clinical care. Governments around the world are investing in large-scale projects to identify the best way to harness genome technology in a medical setting. For example, the Faroe Islands, a sovereign state within the Kingdom of Denmark, is offering sequencing to all of its citizens to understand the basis of genetic diseases prevalent in the isolated population. The U.S. has funded several large grants to study how to best use medical genomic data, and in 2011 it announced an effort to sequence thousands of veterans’ genomes. In 1999, the Chinese government helped establish the Beijing Genomics Institute, which would later become the world’s most prolific genome institute, providing sequences for projects based in China and abroad (see “Inside China’s Genome Factory”).

But the U.K. project stands out for the large number of genomes planned and the integration of the data into a national health-care system that serves more than 60 million people. The initial program will focus on rare inherited diseases, cancer, and infectious pathogens. Initially, the greatest potential will be in giving families long-sought-after answers as to why a rare disorder afflicts them or their children, and “in 10 or 20 years, there may be treatments sprung from it,” says Caulfield.

In addition to exploring how to best handle and use genomic data, the projects taking place in 2014 will give Genomics England time to explore different sequencing technologies offered by commercial providers. The San Diego-based sequencing company Illumina will provide sequencing at existing facilities in England, but Caulfeld emphasizes that the project will want to use the sequencing services of multiple commercial providers. “We are keen to encourage competitiveness in this marketplace as a route to bring down the price for everybody.”

To help control costs for the lofty project, and to foster investment in genomic medicine in the U.K., Genomics England will ask commercial providers to set up sequencing centers in England. “Part of this program is to generate wealth, and that means U.K. jobs,” he says. “We want the sequencing providers to invest in the U.K.” The sequencing centers will be ready by 2015, when the project kicks off in earnest. “Then we will be sequencing 30,000 whole-genome sequences a year,” says Caulfield.

Read the entire article here.

Image: Argonne’s Midwest Center for Structural Genomics deposits 1,000th protein structure. Courtesy of Wikipedia.

BigBang, tD, Technica

Law, Common Sense and Your DNA

Paradoxically the law and common sense often seem to be at odds. Justice may still be blind, at least in most open democracies, but there seems to be no question as to the stupidity of much of our law.

Some examples: in Missouri it’s illegal to drive with an uncaged bear in the car; in Maine, it’s illegal to keep Christmas decorations up after January 14th; in New Jersey, it’s illegal to wear a bulletproof vest while committing murder; in Connecticut, a pickle is not an official, legal pickle unless it can bounce; in Louisiana, you can be fined $500 for instructing a pizza delivery service to deliver pizza to a friend unknowingly.

So, today we celebrate a victory for common sense and justice over thoroughly ill-conceived and badly written law — the U.S. Supreme Court unanimously struck down laws granting patents to corporations for human genes.

Unfortunately though, due to the extremely high financial stakes this is not likely to be the last we hear about big business seeking to patent or control the building blocks to life.

From the WSJ:

The Supreme Court unanimously ruled Thursday that human genes isolated from the body can’t be patented, a victory for doctors and patients who argued that such patents interfere with scientific research and the practice of medicine.

The court was handing down one of its most significant rulings in the age of molecular medicine, deciding who may own the fundamental building blocks of life.

The case involved Myriad Genetics Inc., which holds patents related to two genes, known as BRCA1 and BRCA2, that can indicate whether a woman has a heightened risk of developing breast cancer or ovarian cancer.

Justice Clarence Thomas, writing for the court, said the genes Myriad isolated are products of nature, which aren’t eligible for patents.

“Myriad did not create anything,” Justice Thomas wrote in an 18-page opinion. “To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.”

Even if a discovery is brilliant or groundbreaking, that doesn’t necessarily mean it’s patentable, the court said.

However, the ruling wasn’t a complete loss for Myriad. The court said that DNA molecules synthesized in a laboratory were eligible for patent protection. Myriad’s shares soared after the court’s ruling.

The court adopted the position advanced by the Obama administration, which argued that isolated forms of naturally occurring DNA weren’t patentable, but artificial DNA molecules were.

Myriad also has patent claims on artificial genes, known as cDNA.

The high court’s ruling was a win for a coalition of cancer patients, medical groups and geneticists who filed a lawsuit in 2009 challenging Myriad’s patents. Thanks to those patents, the Salt Lake City company has been the exclusive U.S. commercial provider of genetic tests for breast cancer and ovarian cancer.

“Today, the court struck down a major barrier to patient care and medical innovation,” said Sandra Park of the American Civil Liberties Union, which represented the groups challenging the patents. “Because of this ruling, patients will have greater access to genetic testing and scientists can engage in research on these genes without fear of being sued.”

Myriad didn’t immediately respond to a request for comment.

The challengers argued the patents have allowed Myriad to dictate the type and terms of genetic screening available for the diseases, while also dissuading research by other laboratories.

Read the entire article here.

Image: Gene showing the coding region in a segment of eukaryotic DNA. Courtesy of Wikipedia.

BigBang

Intelligenetics

Intelligenetics isn’t recognized as a real word by Websters or the Oxford English dictionary. We just coined a term that might best represent the growing field of research examining the genetic basis for human intelligence. Of course, it’s not a new subject and comes with many cautionary tales. Past research into the genetic foundations of intelligence has often been misused by one group seeking racial, ethnic or political power over another. However, with strong and appropriate safeguards in place science does have a legitimate place in uncovering what makes some brains excel while others do not.

[div class=attrib]From the Wall Street Journal:[end-div]

At a former paper-printing factory in Hong Kong, a 20-year-old wunderkind named Zhao Bowen has embarked on a challenging and potentially controversial quest: uncovering the genetics of intelligence.

Mr. Zhao is a high-school dropout who has been described as China’s Bill Gates. He oversees the cognitive genomics lab at BGI, a private company that is partly funded by the Chinese government.

At the Hong Kong facility, more than 100 powerful gene-sequencing machines are deciphering about 2,200 DNA samples, reading off their 3.2 billion chemical base pairs one letter at a time. These are no ordinary DNA samples. Most come from some of America’s brightest people—extreme outliers in the intelligence sweepstakes.

The majority of the DNA samples come from people with IQs of 160 or higher. By comparison, average IQ in any population is set at 100. The average Nobel laureate registers at around 145. Only one in every 30,000 people is as smart as most of the participants in the Hong Kong project—and finding them was a quest of its own.

“People have chosen to ignore the genetics of intelligence for a long time,” said Mr. Zhao, who hopes to publish his team’s initial findings this summer. “People believe it’s a controversial topic, especially in the West. That’s not the case in China,” where IQ studies are regarded more as a scientific challenge and therefore are easier to fund.

The roots of intelligence are a mystery. Studies show that at least half of the variation in intelligence quotient, or IQ, is inherited. But while scientists have identified some genes that can significantly lower IQ—in people afflicted with mental retardation, for example—truly important genes that affect normal IQ variation have yet to be pinned down.

The Hong Kong researchers hope to crack the problem by comparing the genomes of super-high-IQ individuals with the genomes of people drawn from the general population. By studying the variation in the two groups, they hope to isolate some of the hereditary factors behind IQ.

Their conclusions could lay the groundwork for a genetic test to predict a person’s inherited cognitive ability. Such a tool could be useful, but it also might be divisive.

“If you can identify kids who are going to have trouble learning, you can intervene” early on in their lives, through special schooling or other programs, says Robert Plomin, a professor of behavioral genetics at King’s College, London, who is involved in the BGI project.

[div class=attrib]Read the entire article following the jump.[end-div]

BigBang

Orphan Genes

DNA is a remarkable substance. It is the fundamental blueprint for biological systems. It is the basis for all complex life on our planet, it enables parents to share characteristics, both good and bad, with their children. Yet the more geneticists learn about the functions of DNA, the more mysteries it presents. One such conundrum is posed by so-called junk DNA and orphan genes — seemingly useless sequences of DNA that perform no function. Or so researchers previously believed.

[div class=attrib]From New Scientist:[end-div]

NOT having any family is tough. Often unappreciated and uncomfortably different, orphans have to fight to fit in and battle against the odds to realise their potential. Those who succeed, from Aristotle to Steve Jobs, sometimes change the world.

Who would have thought that our DNA plays host to a similar cast of foundlings? When biologists began sequencing genomes, they discovered that up to a third of genes in each species seemed to have no parents or family of any kind. Nevertheless, some of these “orphan genes” are high achievers, and a few even seem have played a part in the evolution of the human brain.

But where do they come from? With no obvious ancestry, it was as if these genes had appeared from nowhere, but that couldn’t be true. Everyone assumed that as we learned more, we would discover what had happened to their families. But we haven’t – quite the opposite, in fact.

Ever since we discovered genes, biologists have been pondering their origins. At the dawn of life, the very first genes must have been thrown up by chance. But life almost certainly began in an RNA world, so back then, genes weren’t just blueprints for making enzymes that guide chemical reactions – they themselves were the enzymes. If random processes threw up a piece of RNA that could help make more copies of itself, natural selection would have kicked in straight away.

As living cells evolved, though, things became much more complex. A gene became a piece of DNA coding for a protein. For a protein to be made, an RNA copy of the DNA has to be created. This cannot happen without “DNA switches”, which are actually just extra bits of DNA alongside the protein-coding bits saying “copy this DNA into RNA”. Next, the RNA has to get to the protein-making factories. In complex cells, this requires the presence of yet more extra sequences, which act as labels saying “export me” and “start making the protein from here”.

The upshot is that the chances of random mutations turning a bit of junk DNA into a new gene seem infinitesimally small. As the French biologist François Jacob famously wrote 35 years ago, “the probability that a functional protein would appear de novo by random association of amino acids is practically zero”.

Instead, back in the 1970s it was suggested that the accidental copying of genes can result in a single gene giving rise to a whole family of genes, rather like the way animals branch into families of related species over time. It’s common for entire genes to be inadvertently duplicated. Spare copies are usually lost, but sometimes the duplicates come to share the function of the original gene between them, or one can diverge and take on a new function.

Take the light-sensing pigments known as opsins. The various opsins in our eyes are not just related to each other, they are also related to the opsins found in all other animals, from jellyfish to insects. The thousands of different opsin genes found across the animal kingdom all evolved by duplication, starting with a single gene in a common ancestor living around 700 million years ago (see diagram).

Most genes belong to similar families, and their ancestry can be traced back many millions of years. But when the yeast genome was sequenced around 15 years ago, it was discovered that around a third of yeast genes appeared to have no family. The term orphans (sometimes spelt ORFans) was used to describe individual genes, or small groups of very similar genes, with no known relatives.

“If you see a gene and you can’t find a relative you get suspicious,” says Ken Weiss, who studies the evolution of complex traits at Penn State University. Some suggested orphans were the genetic equivalent of living fossils like the coelacanth, the last surviving members of an ancient family. Others thought they were nothing special, just normal genes whose family hadn’t been found yet. After all, the sequencing of entire genomes had only just begun.

[div class=attrib]Read the entire article after the jump.[end-div]

[div class=attrib]Image: DNA structure. Courtesy of Wikipedia.[end-div]

Technica

Shakespearian Sonnets Now Available on DNA

Shakespeare meet thy DNA. The most famous literary figure in the English language had a recent rendezvous with that most famous and studied of molecules. Together chemists, cell biologists, geneticists and computer scientists are doing some amazing things — storing information using the base-pair sequences of amino-acids on the DNA molecule.

[div class=attrib]From ars technica:[end-div]

It’s easy to get excited about the idea of encoding information in single molecules, which seems to be the ultimate end of the miniaturization that has been driving the electronics industry. But it’s also easy to forget that we’ve been beaten there—by a few billion years. The chemical information present in biomolecules was critical to the origin of life and probably dates back to whatever interesting chemical reactions preceded it.

It’s only within the past few decades, however, that humans have learned to speak DNA. Even then, it took a while to develop the technology needed to synthesize and determine the sequence of large populations of molecules. But we’re there now, and people have started experimenting with putting binary data in biological form. Now, a new study has confirmed the flexibility of the approach by encoding everything from an MP3 to the decoding algorithm into fragments of DNA. The cost analysis done by the authors suggest that the technology may soon be suitable for decade-scale storage, provided current trends continue.

Trinary encoding

Computer data is in binary, while each location in a DNA molecule can hold any one of four bases (A, T, C, and G). Rather than using all that extra information capacity, however, the authors used it to avoid a technical problem. Stretches of a single type of base (say, TTTTT) are often not sequenced properly by current techniques—in fact, this was the biggest source of errors in the previous DNA data storage effort. So for this new encoding, they used one of the bases to break up long runs of any of the other three.

(To explain how this works practically, let’s say the A, T, and C encoded information, while G represents “more of the same.” If you had a run of four A’s, you could represent it as AAGA. But since the G doesn’t encode for anything in particular, TTGT can be used to represent four T’s. The only thing that matters is that there are no more than two identical bases in a row.)

That leaves three bases to encode information, so the authors converted their information into trinary. In all, they encoded a large number of works: all 154 Shakespeare sonnets, a PDF of a scientific paper, a photograph of the lab some of them work in, and an MP3 of part of Martin Luther King’s “I have a dream” speech. For good measure, they also threw in the algorithm they use for converting binary data into trinary.

Once in trinary, the results were encoded into the error-avoiding DNA code described above. The resulting sequence was then broken into chunks that were easy to synthesize. Each chunk came with parity information (for error correction), a short file ID, and some data that indicates the offset within the file (so, for example, that the sequence holds digits 500-600). To provide an added level of data security, 100-bases-long DNA inserts were staggered by 25 bases so that consecutive fragments had a 75-base overlap. Thus, many sections of the file were carried by four different DNA molecules.

And it all worked brilliantly—mostly. For most of the files, the authors’ sequencing and analysis protocol could reconstruct an error-free version of the file without any intervention. One, however, ended up with two 25-base-long gaps, presumably resulting from a particular sequence that is very difficult to synthesize. Based on parity and other data, they were able to reconstruct the contents of the gaps, but understanding why things went wrong in the first place would be critical to understanding how well suited this method is to long-term archiving of data.

[div class=attrib]Read the entire article following the jump.[end-div]

[div class=attrib]Image: Title page of Shakespeare’s Sonnets (1609). Courtesy of Wikipedia / Public Domain.[end-div]

BigBang

The Missing Linc

LincRNA that is. Recent discoveries hint at the potentially crucial role of this new class of genetic material in embryonic development, cell and tissue differentiation and even speciation and evolution.

[div class=attrib]From the Economist:[end-div]

THE old saying that where there’s muck, there’s brass has never proved more true than in genetics. Once, and not so long ago, received wisdom was that most of the human genome—perhaps as much as 99% of it—was “junk”. If this junk had a role, it was just to space out the remaining 1%, the genes in which instructions about how to make proteins are encoded, in a useful way in the cell nucleus.

That, it now seems, was about as far from the truth as it is possible to be. The decade or so since the completion of the Human Genome Project has shown that lots of the junk must indeed have a function. The culmination of that demonstration was the publication, in September, of the results of the ENCODE project. This suggested that almost two-thirds of human DNA, rather than just 1% of it, is being copied into molecules of RNA, the chemical that carries protein-making instructions to the sub-cellular factories which turn those proteins out, and that as a consequence, rather than there being just 23,000 genes (namely, the bits of DNA that encode proteins), there may be millions of them.

The task now is to work out what all these extra genes are up to. And a study just published in Genome Biology, by David Kelley and John Rinn of Harvard University, helps do that for one new genetic class, a type known as lincRNAs. In doing so, moreover, Dr Kelley and Dr Rinn show just how complicated the modern science of genetics has become, and hint also at how animal species split from one another.

Lincs in the chain

Molecules of lincRNA are similar to the messenger-RNA molecules which carry protein blueprints. They do not, however, encode proteins. More than 9,000 sorts are known, and most of those whose job has been tracked down are involved in the regulation of other genes, for example by attaching themselves to the DNA switches that control those genes.

LincRNA is rather odd, though. It often contains members of a second class of weird genetic object. These are called transposable elements (or, colloquially, “jumping genes”, because their DNA can hop from one place to another within the genome). Transposable elements come in several varieties, but one group of particular interest are known as endogenous retroviruses. These are the descendants of ancient infections that have managed to hide away in the genome and get themselves passed from generation to generation along with the rest of the genes.

Dr Kelley and Dr Rinn realised that the movement within the genome of transposable elements is a sort of mutation, and wondered if it has evolutionary consequences. Their conclusion is that it does, for when they looked at the relation between such elements and lincRNA genes, they found some intriguing patterns.

In the first place, lincRNAs are much more likely to contain transposable elements than protein-coding genes are. More than 83% do so, in contrast to only 6% of protein-coding genes.

Second, those transposable elements are particularly likely to be endogenous retroviruses, rather than any of the other sorts of element.

Third, the interlopers are usually found in the bit of the gene where the process of copying RNA from the DNA template begins, suggesting they are involved in switching genes on or off.

And fourth, lincRNAs containing one particular type of endogenous retrovirus are especially active in pluripotent stem cells, the embryonic cells that are the precursors of all other cell types. That indicates these lincRNAs have a role in the early development of the embryo.

Previous work suggests lincRNAs are also involved in creating the differences between various sorts of tissue, since many lincRNA genes are active in only one or a few cell types. Given that their principal job is regulating the activities of other genes, this makes sense.

Even more intriguingly, studies of lincRNA genes from species as diverse as people, fruit flies and nematode worms, have found they differ far more from one species to another than do protein-coding genes. They are, in other words, more species specific. And that suggests they may be more important than protein-coding genes in determining the differences between those species.

[div class=attrib]Read the entire article after the jump.[end-div]

[div class=attrib]Image: Darwin’s finches or Galapagos finches. Darwin, 1845. Courtesy of Wikipedia.[end-div]

BigBang

Telomere Test: A Date With Death

In 1977 Elizabeth Blackburn and Joseph Gall, molecular biologists, discovered the structure of the end caps, known as telomeres, of chromosomes. In 2009, Blackburn and colleagues Carol Greider and Jack Szostak shared the Nobel prize in Physiology or Medicine for discovering the enzyme telomerase, the enzyme responsible for replenishing telomeres.

It turns out that telomeres are rather important. Studies shows that telomeres regulate cell division, and as a consequence directly influence aging and life span. When a cell divides the length of its chromosomal telomeres shortens. Once a telomere is depleted its chromosome, and DNA, can no longer be replicated accurately, and the cell no longer divides, hastening cell death.

[div class=attrib]From the Independent:[end-div]

A blood test to determine how fast someone is ageing has been shown to work on a population of wild birds, the first time the ageing test has been used successfully on animals living outside a laboratory setting.

The test measures the average length of tiny structures on the tips of chromosomes called telomeres which are known to get shorter each time a cell divides during an organism’s lifetime.

Telomeres are believed to act like internal clocks by providing a more accurate estimate of a person’s true biological age rather than their actual chronological age.

This has led some experts to suggest that telomere tests could be used to estimate not only how fast someone is ageing, but possibly how long they have left to live if they die of natural causes.

Telomere tests have been widely used on experimental animals and at least one company is offering a £400 blood test in the UK for people interested in seeing how fast they are ageing based on their average telomere length.

Now scientists have performed telomere tests on an isolated population of songbirds living on an island in the Seychelles and found that the test does indeed accurately predict an animal’s likely lifespan.

“We saw that telomere length is a better indicator of life expectancy than chronological age. So by measuring telomere length we have a way of estimating the biological age of an individual – how much of its life it has used up,” said David Richardson of the University of East Anglia.

The researchers tested the average telomere lengths of a population of 320 Seychelles Warblers living on the remote Cousin Island, which ornithologists have studied for 20 years, documenting the life history of each bird.

“Our results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age,” says the study published in the journal Molecular Ecology.

Studying an island population of wild birds was important because there were no natural predators and little migration, meaning that the scientists could accurately study the link between telomere length and a bird’s natural lifespan.

“We wanted to understand what happens over an entire lifetime, so the Seychelles warbler is an ideal research subject. They are naturally confined to an isolated tropical island, without any predators, so we can follow individuals throughout their lives, right into old age,” Dr Richardson said.

“We investigated whether, at any given age, their telomere lengths could predict imminent death. We found that short and rapidly shortening telomeres were a good indication that the bird would die within a year,” he said.

[div class=attrib]Read the entire article following the jump.[end-div]

[div class=attrib]Infographic courtesy of Independent.[end-div]

BigBang

Us: Perhaps It’s All Due to Gene miR-941

Geneticists have discovered a gene that helps explain how humans and apes diverged from their common ancestor around 6 million years ago.

[div class=attrib]From the Guardian:[end-div]

Researchers have discovered a new gene they say helps explain how humans evolved from chimpanzees.

The gene, called miR-941, appears to have played a crucial role in human brain development and could shed light on how we learned to use tools and language, according to scientists.

A team at the University of Edinburgh compared it to 11 other species of mammals, including chimpanzees, gorillas, mice and rats.

The results, published in Nature Communications, showed that the gene is unique to humans.

The team believe it emerged between six and one million years ago, after humans evolved from apes.

Researchers said it is the first time a new gene carried by humans and not by apes has been shown to have a specific function in the human body.

Martin Taylor, who led the study at the Institute of Genetics and Molecular Medicine at the University of Edinburgh, said: “As a species, humans are wonderfully inventive – we are socially and technologically evolving all the time.

“But this research shows that we are innovating at a genetic level too.

“This new molecule sprang from nowhere at a time when our species was undergoing dramatic changes: living longer, walking upright, learning how to use tools and how to communicate.

“We’re now hopeful that we will find more new genes that help show what makes us human.”

The gene is highly active in two areas of the brain, controlling decision-making and language abilities, with the study suggesting it could have a role in the advanced brain functions that make us human.

[div class=attrib]Read the entire article following the jump.[end-div]

[div class=attrib]Image courtesy of ABCNews.[end-div]

BigBang

Your Molecular Ancestors

[div class=attrib]From Scientific American:[end-div]

Well, perhaps your great-to-the-hundred-millionth-grandmother was.

Understanding the origins of life and the mechanics of the earliest beginnings of life is as important for the quest to unravel the Earth’s biological history as it is for the quest to seek out other life in the universe. We’re pretty confident that single-celled organisms – bacteria and archaea – were the first ‘creatures’ to slither around on this planet, but what happened before that is a matter of intense and often controversial debate.

One possibility for a precursor to these organisms was a world without DNA, but with the bare bone molecular pieces that would eventually result in the evolutionary move to DNA and its associated machinery. This idea was put forward by an influential paper in the journal Nature in 1986 by Walter Gilbert (winner of a Nobel in Chemistry), who fleshed out an idea by Carl Woese – who had earlier identified the Archaea as a distinct branch of life. This ancient biomolecular system was called the RNA-world, since it consists of ribonucleic acid sequences (RNA) but lacks the permanent storage mechanisms of deoxyribonucleic acids (DNA).

A key part of the RNA-world hypothesis is that in addition to carrying reproducible information in their sequences, RNA molecules can also perform the duties of enzymes in catalyzing reactions – sustaining a busy, self-replicating, evolving ecosystem. In this picture RNA evolves away until eventually items like proteins come onto the scene, at which point things can really gear up towards more complex and familiar life. It’s an appealing picture for the stepping-stones to life as we know it.

In modern organisms a very complex molecular structure called the ribosome is the critical machine that reads the information in a piece of messenger-RNA (that has spawned off the original DNA) and then assembles proteins according to this blueprint by snatching amino acids out of a cell’s environment and putting them together. Ribosomes are amazing, they’re also composed of a mix of large numbers of RNA molecules and protein molecules.

But there’s a possible catch to all this, and it relates to the idea of a protein-free RNA-world some 4 billion years ago.

[div class=attrib]Read more after the jump:[end-div]

[div class=attrib]Image: RNA molecule. Courtesy of Wired / Universitat Pampeu Fabra.[end-div]

Idea Soup

Culture, Language and Genes

In the early 19th century Noah Webster set about re-defining written English. His aim was to standardize the spoken word in the fledgling nation and to distinguish American from British usage. In his own words, “as an independent nation, our honor requires us to have a system of our own, in language as well as government.”

He used his dictionary, which still bears his name today, as a tool to cleanse English of its stubborn reliance on aristocratic pedantry and over-reliance on Latin and Greek. He “simplified” the spelling of numerous words that he believed were contsructed with rules that were all too complicated. Thus, “colour” became “color” and “honour” switched to “honor”; “centre” became “center”, “behaviour” to “behavior”, “traveller” to “traveler”.

Webster offers a perfect example of why humanity seems so adept at fragmenting into diverse cultural groups that thrive through mutual uncomprehension. In “Wired for Culture”, evolutionary biologist Mark Pagel offers a compelling explanation based on that small, yet very selfish biological building block, the gene.

[div class=attrib]From the Wall Street Journal:[end-div]

The island of Gaua, part of Vanuatu in the Pacific, is just 13 miles across, yet it has five distinct native languages. Papua New Guinea, an area only slightly bigger than Texas, has 800 languages, some spoken by just a few thousand people.

…

Evolutionary biologists have long gotten used to the idea that bodies are just genes’ ways of making more genes, survival machines that carry genes to the next generation. Think of a salmon struggling upstream just to expend its body (now expendable) in spawning. Dr. Pagel’s idea is that cultures are an extension of this: that the way we use culture is to promote the long-term interests of our genes.

It need not be this way. When human beings’ lives became dominated by culture, they could have adopted habits that did not lead to having more descendants. But on the whole we did not; we set about using culture to favor survival of those like us at the expense of other groups, using religion, warfare, cooperation and social allegiance. As Dr. Pagel comments: “Our genes’ gamble at handing over control to…ideas paid off handsomely” in the conquest of the world.

What this means, he argues, is that if our “cultures have promoted our genetic interests throughout our history,” then our “particular culture is not for us, but for our genes.”

We’re expendable. The allegiance we feel to one tribe—religious, sporting, political, linguistic, even racial—is a peculiar mixture of altruism toward the group and hostility to other groups. Throughout history, united groups have stood, while divided ones fell.

Language is the most striking exemplar of Dr. Pagel’s thesis. He calls language “one of the most powerful, dangerous and subversive traits that natural selection has ever devised.” He draws attention to the curious parallels between genetics and linguistics. Both are digital systems, in which words or base pairs are recombined to make an infinite possibility of messages. (Elsewhere I once noted the numerical similarity between Shakespeare’s vocabulary of about 20,000 distinct words and his genome of about 21,000 genes).

Dr. Pagel points out that language is a “technology for rewiring other people’s minds…without either of you having to perform surgery.” But natural section was unlikely to favor such a technology if it helped just the speaker, or just the listener, at the expense of the other. Rather, he says that, just as the language of the genes promotes its own survival via a larger cooperative entity called the body, so language itself endures via the survival of the individual and the tribe.

[div class=attrib]Read the entire article here.[end-div]

[div class=attrib]Image courtesy of PA / Daily Mail.[end-div]

BigBang

Weight Loss and the Coordinated Defense Mechanism

New research into obesity and weight loss shows us why it’s so hard to keep weight lost from dieting from returning. The good news is that weight (re-)gain is not all due to a simple lack of control and laziness. However, the bad news is that keeping one’s weight down may be much more difficult due to the body’s complex defense mechanism.

Tara Parker-Pope over at the Well blog reviews some of the new findings, which seem to point the finger at a group hormones and specific genes that work together to help us regain those lost pounds.

[div class=attrib]From the New York Times:[end-div]

For 15 years, Joseph Proietto has been helping people lose weight. When these obese patients arrive at his weight-loss clinic in Australia, they are determined to slim down. And most of the time, he says, they do just that, sticking to the clinic’s program and dropping excess pounds. But then, almost without exception, the weight begins to creep back. In a matter of months or years, the entire effort has come undone, and the patient is fat again. “It has always seemed strange to me,” says Proietto, who is a physician at the University of Melbourne. “These are people who are very motivated to lose weight, who achieve weight loss most of the time without too much trouble and yet, inevitably, gradually, they regain the weight.”

Anyone who has ever dieted knows that lost pounds often return, and most of us assume the reason is a lack of discipline or a failure of willpower. But Proietto suspected that there was more to it, and he decided to take a closer look at the biological state of the body after weight loss.

Beginning in 2009, he and his team recruited 50 obese men and women. The men weighed an average of 233 pounds; the women weighed about 200 pounds. Although some people dropped out of the study, most of the patients stuck with the extreme low-calorie diet, which consisted of special shakes called Optifast and two cups of low-starch vegetables, totaling just 500 to 550 calories a day for eight weeks. Ten weeks in, the dieters lost an average of 30 pounds.

At that point, the 34 patients who remained stopped dieting and began working to maintain the new lower weight. Nutritionists counseled them in person and by phone, promoting regular exercise and urging them to eat more vegetables and less fat. But despite the effort, they slowly began to put on weight. After a year, the patients already had regained an average of 11 of the pounds they struggled so hard to lose. They also reported feeling far more hungry and preoccupied with food than before they lost the weight.

While researchers have known for decades that the body undergoes various metabolic and hormonal changes while it’s losing weight, the Australian team detected something new. A full year after significant weight loss, these men and women remained in what could be described as a biologically altered state. Their still-plump bodies were acting as if they were starving and were working overtime to regain the pounds they lost. For instance, a gastric hormone called ghrelin, often dubbed the “hunger hormone,” was about 20 percent higher than at the start of the study. Another hormone associated with suppressing hunger, peptide YY, was also abnormally low. Levels of leptin, a hormone that suppresses hunger and increases metabolism, also remained lower than expected. A cocktail of other hormones associated with hunger and metabolism all remained significantly changed compared to pre-dieting levels. It was almost as if weight loss had put their bodies into a unique metabolic state, a sort of post-dieting syndrome that set them apart from people who hadn’t tried to lose weight in the first place.

“What we see here is a coordinated defense mechanism with multiple components all directed toward making us put on weight,” Proietto says. “This, I think, explains the high failure rate in obesity treatment.”

[div class=attrib]Read the entire article here.[end-div]

[div class=attrib]Image courtesy of Science Daily.[end-div]

BigBang

When Will I Die?

Would you like to know when you will die?

This is a fundamentally personal and moral question which many may prefer to keep unanswered.  That said, while scientific understanding of aging is making great strides it cannot yet provide an answer to the question. Though it may only be a matter of time.

Giles Tremlett over at the Guardian gives us a personal account of the fascinating science of telomeres, the end-caps on our chromosomes, and why they potentially hold a key to that most fateful question.

[div class=attrib]From the Guardian:[end-div]

As a taxi takes me across Madrid to the laboratories of Spain’s National Cancer Research Centre, I am fretting about the future. I am one of the first people in the world to provide a blood sample for a new test, which has been variously described as a predictor of how long I will live, a waste of time or a handy indicator of how well (or badly) my body is ageing. Today I get the results.

Some newspapers, to the dismay of the scientists involved, have gleefully announced that the test – which measures the telomeres (the protective caps on the ends of my chromosomes) – can predict when I will die. Am I about to find out that, at least statistically, my days are numbered? And, if so, might new telomere research suggesting we can turn back the hands of the body’s clock and make ourselves “biologically younger” come to my rescue?

The test is based on the idea that biological ageing grinds at your telomeres. And, although time ticks by uniformly, our bodies age at different rates. Genes, environment and our own personal habits all play a part in that process. A peek at your telomeres is an indicator of how you are doing. Essentially, they tell you whether you have become biologically younger or older than other people born at around the same time.

The key measure, explains María Blasco, a 45-year-old molecular biologist, head of Spain’s cancer research centre and one of the world’s leading telomere researchers, is the number of short telomeres. Blasco, who is also one of the co-founders of the Life Length company which is offering the tests, says that short telomeres do not just provide evidence of ageing. They also cause it. Often compared to the plastic caps on a shoelace, there is a critical level at which the fraying becomes irreversible and triggers cell death. “Short telomeres are causal of disease because when they are below a [certain] length they are damaging for the cells. The stem cells of our tissues do not regenerate and then we have ageing of the tissues,” she explains. That, in a cellular nutshell, is how ageing works. Eventually, so many of our telomeres are short that some key part of our body may stop working.

The research is still in its early days but extreme stress, for example, has been linked to telomere shortening. I think back to a recent working day that took in three countries, three news stories, two international flights, a public lecture and very little sleep. Reasonable behaviour, perhaps, for someone in their 30s – but I am closer to my 50s. Do days like that shorten my expected, or real, life-span?

[div class=attrib]Read more of this article here.[end-div]

[div class]Image: chromosomes capped by telomeres (white), courtesy of Wikipedia.[end-div]

BigBang

Human Evolution Marches On

[div class=attrib]From Wired:[end-div]

Though ongoing human evolution is difficult to see, researchers believe they’ve found signs of rapid genetic changes among the recent residents of a small Canadian town.

Between 1800 and 1940, mothers in Ile aux Coudres, Quebec gave birth at steadily younger ages, with the average age of first maternity dropping from 26 to 22. Increased fertility, and thus larger families, could have been especially useful in the rural settlement’s early history.

According to University of Quebec geneticist Emmanuel Milot and colleagues, other possible explanations, such as changing cultural or environmental influences, don’t fit. The changes appear to reflect biological evolution.

“It is often claimed that modern humans have stopped evolving because cultural and technological advancements have annihilated natural selection,” wrote Milot’s team in their Oct. 3 Proceedings of the National Academy of Sciences paper. “Our study supports the idea that humans are still evolving. It also demonstrates that microevolution is detectable over just a few generations.”

…

Milot’s team based their study on detailed birth, marriage and death records kept by the Catholic church in Ile aux Coudres, a small and historically isolated French-Canadian island town in the Gulf of St. Lawrence. It wasn’t just the fact that average first birth age — a proxy for fertility — dropped from 26 to 22 in 140 years that suggested genetic changes. After all, culture or environment might have been wholly responsible, as nutrition and healthcare are for recent, rapid changes in human height. Rather, it was how ages dropped that caught their eye.

The patterns fit with models of gene-influenced natural selection. Moreover, thanks to the detailed record-keeping, it was possible to look at other possible explanations. Were better nutrition responsible, for example, improved rates of infant and juvenile mortality should have followed; they didn’t. Neither did the late-19th century transition from farming to more diversified professions.

[div class=attrib]Read more here.[end-div]

Idea Soup

Sergey Brin’s Search for a Parkinson’s Cure

[div class=attrib]From Wired:[end-div]

Several evenings a week, after a day’s work at Google headquarters in Mountain View, California, Sergey Brin drives up the road to a local pool. There, he changes into swim trunks, steps out on a 3-meter springboard, looks at the water below, and dives.

Brin is competent at all four types of springboard diving—forward, back, reverse, and inward. Recently, he’s been working on his twists, which have been something of a struggle. But overall, he’s not bad; in 2006 he competed in the master’s division world championships. (He’s quick to point out he placed sixth out of six in his event.)

The diving is the sort of challenge that Brin, who has also dabbled in yoga, gymnastics, and acrobatics, is drawn to: equal parts physical and mental exertion. “The dive itself is brief but intense,” he says. “You push off really hard and then have to twist right away. It does get your heart rate going.”

There’s another benefit as well: With every dive, Brin gains a little bit of leverage—leverage against a risk, looming somewhere out there, that someday he may develop the neurodegenerative disorder Parkinson’s disease. Buried deep within each cell in Brin’s body—in a gene called LRRK2, which sits on the 12th chromosome—is a genetic mutation that has been associated with higher rates of Parkinson’s.

Not everyone with Parkinson’s has an LRRK2 mutation; nor will everyone with the mutation get the disease. But it does increase the chance that Parkinson’s will emerge sometime in the carrier’s life to between 30 and 75 percent. (By comparison, the risk for an average American is about 1 percent.) Brin himself splits the difference and figures his DNA gives him about 50-50 odds.

That’s where exercise comes in. Parkinson’s is a poorly understood disease, but research has associated a handful of behaviors with lower rates of disease, starting with exercise. One study found that young men who work out have a 60 percent lower risk. Coffee, likewise, has been linked to a reduced risk. For a time, Brin drank a cup or two a day, but he can’t stand the taste of the stuff, so he switched to green tea. (“Most researchers think it’s the caffeine, though they don’t know for sure,” he says.) Cigarette smokers also seem to have a lower chance of developing Parkinson’s, but Brin has not opted to take up the habit. With every pool workout and every cup of tea, he hopes to diminish his odds, to adjust his algorithm by counteracting his DNA with environmental factors.

“This is all off the cuff,” he says, “but let’s say that based on diet, exercise, and so forth, I can get my risk down by half, to about 25 percent.” The steady progress of neuroscience, Brin figures, will cut his risk by around another half—bringing his overall chance of getting Parkinson’s to about 13 percent. It’s all guesswork, mind you, but the way he delivers the numbers and explains his rationale, he is utterly convincing.

Brin, of course, is no ordinary 36-year-old. As half of the duo that founded Google, he’s worth about $15 billion. That bounty provides additional leverage: Since learning that he carries a LRRK2 mutation, Brin has contributed some $50 million to Parkinson’s research, enough, he figures, to “really move the needle.” In light of the uptick in research into drug treatments and possible cures, Brin adjusts his overall risk again, down to “somewhere under 10 percent.” That’s still 10 times the average, but it goes a long way to counterbalancing his genetic predisposition.

It sounds so pragmatic, so obvious, that you can almost miss a striking fact: Many philanthropists have funded research into diseases they themselves have been diagnosed with. But Brin is likely the first who, based on a genetic test, began funding scientific research in the hope of escaping a disease in the first place.

[div class=attrib]More from theSource here.[end-div]

BigBang

Immaculate creation: birth of the first synthetic cell

[div class=attrib]From the New Scientist:[end-div]

For the first time, scientists have created life from scratch – well, sort of. Craig Venter‘s team at the J. Craig Venter Institute in Rockville, Maryland, and San Diego, California, has made a bacterial genome from smaller DNA subunits and then transplanted the whole thing into another cell. So what exactly is the science behind the first synthetic cell, and what is its broader significance?

What did Venter’s team do?

The cell was created by stitching together the genome of a goat pathogen called Mycoplasma mycoides from smaller stretches of DNA synthesised in the lab, and inserting the genome into the empty cytoplasm of a related bacterium. The transplanted genome booted up in its host cell, and then divided over and over to make billions of M. mycoides cells.

Venter and his team have previously accomplished both feats – creating a synthetic genome and transplanting a genome from one bacterium into another – but this time they have combined the two.

“It’s the first self-replicating cell on the planet that’s parent is a computer,” says Venter, referring to the fact that his team converted a cell’s genome that existed as data on a computer into a living organism.

How can they be sure that the new bacteria are what they intended?

Venter and his team introduced several distinctive markers into their synthesised genome. All of them were found in the synthetic cell when it was sequenced.

These markers do not make any proteins, but they contain the names of 46 scientists on the project and several quotations written out in a secret code. The markers also contain the key to the code.

Crack the code and you can read the messages, but as a hint, Venter revealed the quotations: “To live, to err, to fall, to triumph, to recreate life out of life,” from James Joyce’s A Portrait of the Artist as a Young Man; “See things not as they are but as they might be,” which comes from American Prometheus, a biography of nuclear physicist Robert Oppenheimer; and Richard Feynman’s famous words: “What I cannot build I cannot understand.”

Does this mean they created life?

It depends on how you define “created” and “life”. Venter’s team made the new genome out of DNA sequences that had initially been made by a machine, but bacteria and yeast cells were used to stitch together and duplicate the million base pairs that it contains. The cell into which the synthetic genome was then transplanted contained its own proteins, lipids and other molecules.

Venter himself maintains that he has not created life . “We’ve created the first synthetic cell,” he says. “We definitely have not created life from scratch because we used a recipient cell to boot up the synthetic chromosome.”

Whether you agree or not is a philosophical question, not a scientific one as there is no biological difference between synthetic bacteria and the real thing, says Andy Ellington, a synthetic biologist at the University of Texas in Austin. “The bacteria didn’t have a soul, and there wasn’t some animistic property of the bacteria that changed,” he says.

What can you do with a synthetic cell?

Venter’s work was a proof of principle, but future synthetic cells could be used to create drugs, biofuels and other useful products. He is collaborating with Exxon Mobil to produce biofuels from algae and with Novartis to create vaccines.

“As soon as next year, the flu vaccine you get could be made synthetically,” Venter says.

Ellington also sees synthetic bacteria as having potential as a scientific tool. It would be interesting, he says, to create bacteria that produce a new amino acid – the chemical units that make up proteins – and see how these bacteria evolve, compared with bacteria that produce the usual suite of amino acids. “We can ask these questions about cyborg cells in ways we never could before.”

[div class=attrib]More from theSource here.[end-div]

BigBang

The Search for Genes Leads to Unexpected Places

[div class=attrib]From The New York Times:[end-div]

Edward M. Marcotte is looking for drugs that can kill tumors by stopping blood vessel growth, and he and his colleagues at the University of Texas at Austin recently found some good targets — five human genes that are essential for that growth. Now they’re hunting for drugs that can stop those genes from working. Strangely, though, Dr. Marcotte did not discover the new genes in the human genome, nor in lab mice or even fruit flies. He and his colleagues found the genes in yeast.

“On the face of it, it’s just crazy,” Dr. Marcotte said. After all, these single-cell fungi don’t make blood vessels. They don’t even make blood. In yeast, it turns out, these five genes work together on a completely unrelated task: fixing cell walls.

Crazier still, Dr. Marcotte and his colleagues have discovered hundreds of other genes involved in human disorders by looking at distantly related species. They have found genes associated with deafness in plants, for example, and genes associated with breast cancer in nematode worms. The researchers reported their results recently in The Proceedings of the National Academy of Sciences.

The scientists took advantage of a peculiar feature of our evolutionary history. In our distant, amoeba-like ancestors, clusters of genes were already forming to work together on building cell walls and on other very basic tasks essential to life. Many of those genes still work together in those same clusters, over a billion years later, but on different tasks in different organisms.

[div class=attrib]More from theSource here.[end-div]

BigBang

Unlocking the Secrets of Longevity Genes

[div class=attrib]From Scientific American:[end-div]

A handful of genes that control the body’s defenses during hard times can also dramatically improve health and prolong life in diverse organisms. Understanding how they work may reveal the keys to extending human life span while banishing diseases of old age.

You can assume quite a bit about the state of a used car just from its mileage and model year. The wear and tear of heavy driving and the passage of time will have taken an inevitable toll. The same appears to be true of aging in people, but the analogy is flawed because of a crucial difference between inanimate machines and living creatures: deterioration is not inexorable in biological systems, which can respond to their environments and use their own energy to defend and repair themselves.

At one time, scientists believed aging to be not just deterioration but an active continuation of an organism’s genetically programmed development. Once an individual achieved maturity, “aging genes” began to direct its progress toward the grave. This idea has been discredited, and conventional wisdom now holds that aging really is just wearing out over time because the body’s normal maintenance and repair mechanisms simply wane. Evolutionary natural selection, the logic goes, has no reason to keep them working once an organism has passed its reproductive age.

[div class=attrib]More from theSource here.[end-div]