“Ever since a monk called Mendel started breeding pea plants we’ve been learning about our genomes. In 1953, Watson, Crick and Franklin described the structure of the molecule that makes up our genomes: the DNA double helix. Then, in 2001, scientists wrote down the entire 3-billion letter code contained in the average human genome. Now they’re trying to interpret that code; to work out how it’s used to make different types of cells and different people. The ENCODE project, as it’s called, is the latest chapter in the story of you.”
Tag Archive: DNA
A bioengineer and geneticist at Harvard’s Wyss Institute have successfully stored 5.5 petabits of data — around 700 terabytes — in a single gram of DNA, smashing the previous DNA data density record by a thousand times.
The work, carried out by George Church and Sri Kosuri, basically treats DNA as just another digital storage device. Instead of binary data being encoded as magnetic regions on a hard drive platter, strands of DNA that store 96 bits are synthesized, with each of the bases (TGAC) representing a binary value (T and G = 1, A and C = 0).
To read the data stored in DNA, you simply sequence it — just as if you were sequencing the human genome — and convert each of the TGAC bases back into binary. To aid with sequencing, each strand of DNA has a 19-bit address block at the start (the red bits in the image below) — so a whole vat of DNA can be sequenced out of order, and then sorted into usable data using the addresses.
Why do humans and their primate cousins get more stress-related diseases than any other member of the animal kingdom? The answer, says Stanford neuroscientist Robert Sapolsky, is that people, apes and monkeys are highly intelligent, social creatures with far too much spare time on their hands. “Primates are super smart and organized just enough to devote their free time to being miserable to each other and stressing each other out,” he said. “But if you get chronically, psychosocially stressed, you’re going to compromise your health. So, essentially, we’ve evolved to be smart enough to make ourselves sick.”
A professor of biological sciences and of neurology and neurological sciences, Sapolsky has spent more than three decades studying the physiological effects of stress on health. His pioneering work includes ongoing studies of laboratory rats and wild baboons in the African wilderness. All vertebrates respond to stressful situations by releasing hormones, such as adrenalin and glucocorticoids, which instantaneously increase the animal’s heart rate and energy level. “The stress response is incredibly ancient evolutionarily,” Sapolsky said. “Fish, birds and reptiles secrete the same stress hormones we do, yet their metabolism doesn’t get messed up the way it does in people and other primates.”
To understand why, he said, “just look at the dichotomy between what your body does during real stress—for example, something is intent on eating you and you’re running for your life—versus what your body does when you’re turning on the same stress response for months on end for purely psychosocial reasons.”
In the short term, he explained, stress hormones are “brilliantly adapted” to help you survive an unexpected threat. “You mobilize energy in your thigh muscles, you increase your blood pressure and you turn off everything that’s not essential to surviving, such as digestion, growth and reproduction,” he said. “You think more clearly, and certain aspects of learning and memory are enhanced. All of that is spectacularly adapted if you’re dealing with an acute physical stressor—a real one.”
The technique uses two proteins adapted from viruses to “flip” the DNA bits.
Though it is at an early stage, the advance could help pave the way for computing and memory storage within biological systems.
A team reporting in Proceedings of the National Academy of Sciences say the tiny information storehouses may also be used to study cancer and aging.
The team, from Stanford University’s bioengineering department, has been trying for three years to fine-tune the biological recipe they use to change the bits’ value.
The bits comprise short sections of DNA that can, under the influence of two different proteins, be made to point in one of two directions within the chromosomes of the bacterium E. coli.
The data are then “read out” as the sections were designed to glow green or red when under illumination, depending on their orientation.
By duplicating itself two and a half million years ago the gene could have given early human brains the power of speech and invention, leaving cousins such as chimpanzees behind.
The gene, known as SRGAP2, helps control the development of the neocortex – the part of the brain responsible for higher functions like language and conscious thought.
Having an extra copies slowed down the development of the brain, allowing it to forge more connections between nerve cells and in doing so grow bigger and more complex, researchers said.
In a study published in the Cell journal, the scientists reported that the gene duplicated about 3.5 million years ago to create a “daughter” gene, and again a million years later creating a “granddaughter” copy.
Although humans and chimpanzees separated six million years ago, we still share 96 per cent of our genome and the gene is one of only about 30 which have copied themselves since that time.
The first duplication was relatively inactive but the second occurred at about the time when primitive Homo separated from its brother Australopithecus species and began developing more sophisticated tools and behaviours.
Evan Eichler at the University of Washington, who led the research, said the benefit of the duplication would have been instant, meaning human ancestors could have distanced themselves from rival species within a generation.
He said: “This innovation could not have happened without that incomplete duplication. Our data suggest a mechanism where incomplete duplication of this gene created a novel function ‘at birth’.”
Once considered unimportant “junk DNA,” scientists have learned that non-coding RNA (ncRNA) — RNA molecules that do not translate into proteins — play a crucial role in cellular function. Mutations in ncRNA are associated with a number of conditions, such as cancer, autism, and Alzheimer’s disease.
Now, through the use of “deep sequencing,” a technology used to sequence the genetic materials of the human genome, Dr. Noam Shomron of Tel Aviv University’s Sackler Faculty of Medicine has discovered that when infected with a virus, ncRNA gives off biological signals that indicate the presence of an infectious agent, known as a pathogen. Not only does this finding give researchers a more complete picture of the interactions between pathogens and the body, but it provides scientists with a new avenue for fighting off infections.
His findings have been published in the journal Nucleic Acid Research.
“If we see that the number of particular RNA molecules increases during a specific viral infection, we can develop treatments to stop or slow their proliferation,” explains Dr. Shomron.
In the lab, the researchers conducted a blind study in which some cells were infected with the HIV virus and others were left uninfected. Using the deep sequencer, which can read tens of millions of sequences per experiment, they analyzed the ncRNA to discover if the infection could be detected in non-coding DNA materials. The researchers were able to identify with 100% accuracy both infected and non-infected cells — all because the ncRNA was giving off significant signals, explains Dr. Shomron.
Traces of ancient viruses which infected our ancestors millions of years ago are more widespread in us than previously thought.
A study shows how extensively viruses from as far back as the dinosaur era still thrive in our genetic material.
It sheds light on the origins of a big proportion of our genetic material, much of which is still not understood.
The scientists investigated the genomes of 38 mammals including humans, mice, rats, elephants and dolphins.
The research was carried out at Oxford University, the Aaron Diamond AIDS Research Centre in New York and the Rega Institute in Belgium.
One of the viruses was found to have invaded the genome of a common ancestor around 100 million years ago with its remnants discovered in almost every mammal in the study.
Another infected an early primate with the result that it was found in apes, humans and other primates as well.
The work established that many of these viruses lost the ability to transfer from one cell to another.
Instead they evolved to stay within their host cell where they have profilerated very effectively – spending their entire life cycle within the cell.
Researchers moved a step closer to creating new life forms in the laboratory after they demonstrated an artificial genetic material called XNA can be replicated in the test tube much like real DNA. X, which in this case stands for “xeno” indicates the replacement of the helical backbone of the new molecule.
Scientists at the Medical Research Council Laboratory of Molecular Biology in the U.K. demonstrated for the first time a way to extract information from the artificial genetic molecules and mass produce copies of them.
The research, published today in the journal Science, shows that DNA and its sister molecule RNA may not be the only chemical structures upon which a living unit can be based.
“Life is based on this amazing ability of DNA and RNA to store and propagate information,” saidPhilipp Holliger, a Medical Research Council molecular biologist and senior author on the study. “We have shown that the basic functions of DNA and RNA can be recapitulated” with new artificial molecules.
Vitor Pinheiro and colleagues from Philipp’s group used sophisticated protein engineering techniques to adapt enzymes, that in nature synthesise and replicate DNA, to establish six new genetic systems based on synthetic nucleic acids. These have the same bases as DNA but the ribose linkage between them is replaced by quite different structures.
In doing this they showed that there is no functional imperative limiting genetic information storage to RNA and DNA. Therefore, the discovery has implications for the understanding of life on Earth. As other informational molecules can be robustly synthesised and replicated, the emergence of life on Earth is likely to reflect the abundance of RNA (and DNA) precursors in early Earth.
The scientists invented a lab method for making copies of synthetic DNA. They also developed a way to make XNA fragments that evolve with desired properties.
DNA sequencing is becoming both faster and cheaper. Now, it is also becoming tinier.
A British company said on Friday that by the end of the year it would begin selling a disposable gene sequencing device that is the size of a USB memory stick and plugs into a laptop computer to deliver its results.
The device, expected to cost less than $900, could allow small sequencing jobs to be done by researchers who cannot afford the $50,000 to $750,000 needed to buy a sequencing machine.
It might also help doctors to sequence genes at a patient’s bedside, wildlife biologists to study genes in the field, or food inspectors to identify pathogens.
“You don’t need to buy instruments,” Clive G. Brown, the chief technology officer of the company, Oxford Nanopore Technologies, said in an interview. “It’s pay-as-you-go sequencing.”
Oxford presented details of the device, as well as of a new, somewhat larger sequencer that it also plans to begin selling late this year, at the Advances in Genome Biology and Technology conference in Marco Island, Fla., which has become the sequencing industry’s annual boast-fest.
Both the tiny MinIon and the larger GridIon look likely to be the first sequencers to use nanopore sequencing, in which a strand of DNA is read as it is pulled through a microscopic hole, sort of like a noodle being slurped through rounded lips.
Take note, DNA and RNA: it’s not all about you. Life on Earth may have begun with a splash of TNA – a different kind of genetic material altogether.
Because RNA can do many things at once, those studying the origins of life have long thought that it was the first genetic material. But the discovery that a chemical relative called TNA can perform one of RNA’s defining functions calls this into question. Instead, the very first forms of life may have used a mix of genetic materials.
RNA, DNA… TNA
Today, most life bar some viruses uses DNA to store information, and RNA to execute the instructions encoded by that DNA. However, many biologists think that the earliest forms of life used RNA for everything, with little or no help from DNA.
A key piece of evidence for this “RNA world” hypothesis is that RNA is a jack of all trades. It can both store genetic information and act as an enzyme, seemingly making it the ideal molecule to start life from scratch.
Now it seems TNA might have been just as capable, although it is not found in nature today.
Family living conditions in childhood are associated with significant effects in DNA that persist well into middle age, according to new research by Canadian and British scientists.
The team, based at McGill University in Montreal, University of British Columbia in Vancouver and the UCL Institute of Child Health in London looked for gene methylation associated with social and economic factors in early life. They found clear differences in gene methylation between those brought up in families with very high and very low standards of living. More than twice as many methylation differences were associated with the combined effect of the wealth, housing conditions and occupation of parents (that is, early upbringing) than were associated with the current socio-economic circumstances in adulthood. (1252 differences as opposed to 545).
The findings, published online today in the International Journal of Epidemiology, could provide major evidence as to why the health disadvantages known to be associated with low socio-economic position can remain for life, despite later improvement in living conditions. The study set out to explore the way early life conditions might become ‘biologically-embedded’ and so continue to influence health, for better or worse, throughout life. The scientists decided to look at DNA methylation, a so-called epigenetic modification that is linked to enduring changes in gene activity and hence potential health risks. (Broadly, methylation of a gene at a significant point in the DNA reduces the activity of the gene.)
Fat cells of an untreated mouse, at left, where senescent cells remain, are smaller than in a mouse with senescent cells removed.
The findings raise the prospect that any therapy that rids the body of senescent cells would protect it from the ravages of aging. But many more tests will be needed before scientists know if drugs can be developed to help people live longer.
Senescent cells accumulate in aging tissues, like arthritic knees, cataracts and the plaque that may line elderly arteries. The cells secrete agents that stimulate the immune system and cause low-level inflammation. Until now, there has been no way to tell if the presence of the cells is good, bad or indifferent.
The answer turns out to be that the cells hasten aging in the tissues in which they accumulate. In a delicate feat of genetic engineering, a research team led by Darren J. Baker and Jan M. van Deursen at the Mayo Clinic in Rochester, Minn., has generated a strain of mouse in which all the senescent cells can be purged by giving the mice a drug that forces the cells to self-destruct.
The mythical “$1,000 genome” is almost upon us, said Jonathan Rothberg, CEO of sequencing technology company Ion Torrent, at MIT’s Emerging Technology conference. If his prediction comes true, it will represent an astonishing triumph in rapid technological development. The rate at which genome sequencing has become more affordable is faster than Moore’s law.
“By this time next year sequencing human genomes as fast and cheap as bacterial genome,” said Rothberg. (Earlier, he’d commented that his company can now do an entire bacterial genome in about two hours.)
I was in the room on October 19 when he said it, and I would have thought it pure hubris were it not for Rothberg’s incredible track record in this area, from founding successful previous-generation sequencing company 454 Life Sciences to recent breakthroughs made with the same technology he proposes will get us to the $1,000 genome.
This technology, called, called the Personal Genome Machine, is already being used to determine which mutations are present in the genomes of patients’ cancers.