New study hints at spontaneous appearance of primordial DNA

The image shows a droplet of condensed nano-DNA and within it smaller drops of its liquid crystal phase which show up in polarized light on the left. The liquid crystal droplets act as “micro-reactors" where short DNA can join together into long polymer chains without the aid of biological mechanisms. Image courtesy Noel Clark, University of Colorado

The image shows a droplet of condensed nano-DNA and within it smaller drops of its liquid crystal phase which show up in polarized light on the left. The liquid crystal droplets act as “micro-reactors” where short DNA can join together into long polymer chains without the aid of biological mechanisms. Image courtesy Noel Clark, University of Colorado

The self-organization properties of DNA-like molecular fragments four billion years ago may have guided their own growth into repeating chemical chains long enough to act as a basis for primitive life, says a new study by the University of Colorado Boulder and the University of Milan.

While studies of ancient mineral formations contain evidence for the evolution of bacteria from 3.5 to 3.8 billion years ago — just half a billion years after the stabilization of Earth’s crust — what might have preceded the formation of such unicellular organisms is still a mystery. The new findings suggest a novel scenario for the non-biological origins of nucleic acids, which are the building blocks of living organisms, said CU-Boulder physics Professor Noel Clark, a study co-author. Continue reading New study hints at spontaneous appearance of primordial DNA

Why an extra helix becomes a third wheel in cell biology

dna3Every high school biology student knows the structure of DNA is a double helix, but after DNA is converted into RNA, parts of RNA also commonly fold into the same spiral staircase shape.

In a literal scientific twist, researchers are finding examples of a third strand that wraps itself around RNA like a snake, a structure rarely found in nature. Researchers recently have discovered evidence of a triple helix forming at the end of MALAT1, a strand of RNA that does not code for proteins. Yale postdoctoral fellow Jessica Brown and her colleagues working in the labs of Joan A. Steitz and Thomas A. Steitz describe the bonds that maintain the structure of a rare triple helix.

This extra strand of RNA, which is seen in the accompanying movie, prevents degradation of MALAT1. The formation of a triple helix explains how MALAT1 accumulates to very high levels in cancer cells, allowing MALAT1 to promote metastasis of lung cancer and likely other cancers.

The work is published in the journal Nature Structural and Molecular Biology.

Model and electron micrograph of a DNA fibre

You can’t see DNA unless you look properly

We know what DNA looks like and have been looking at it for nearly 60 years. So why has a new analysis of DNA structure been reported so poorly?

by Stephen Curry

I’m not an angry man but a new analysis of the structure of DNA using electron microscopy made me cross yesterday. It wasn’t the fault of the scientists involved, but the sloppy way the result was reported that got my scientific goat.

The structure of DNA was first determined almost 60 years ago by Watson’s and Crick’s famous analysis of the scattering patterns recorded by Maurice Wilkins and Rosalind Franklin as they fired beams of X-rays at narrow fibres of the stuff. We have had a long time to refine and digest this result so I was surprised to run across so much inaccurate information in the internet digests of the new finding, reported in the journal Nano Letters by an Italian group led by Enzo di Fabrizio.

The web-site headlined George Dvorsky’s piece “Scientists snap a picture of DNA’s double helix for the very first time.” No, they hadn’t. The accompanying article interspersed fact with fancy before finally concluding that the new imaging technique would enable us to see “how it interacts with proteins and RNA”. No, it won’t.

I’ll explain why in a minute but first let’s look at New Scientist’s coverage of the same paper. This was a more measured and more accurate account of the new result but the piece got off to a bad start. Roland Pease’s article claimed that “an electron microscope has captured the famous Watson-Crick double helix in all its glory.” But it clearly hadn’t. The accompanying image was fuzzy and did not show a double helix that resembled the one described by Watson and Crick

Model and electron micrograph of a DNA fibre

Model and electron micrograph of a DNA fibre

Pease followed this up with the same ill-founded claim that the new method would allow researchers to see how other biomolecules interact with DNA. I’m not sure where this claim has come from because it’s not in the paper. A faulty press release perhaps?

Finally Alex Wild blogged about the article at Scientific American. His post, riskily titled “What DNA actually looks like” claimed that the paper reports “the first ever microscope image of an isolated DNA molecule”. If he had take the nanotrouble to type “electron micrograph DNA” into a Google search, he would have seen there are plenty of earlier microscope images of DNA. If he had looked more carefully at the abstract of the paper — helpfully illustrated in this instance (see above) — he would have seen that the sample was in fact a bundle of DNA molecules, not an isolated one. Sheesh.

Why make a fuss about this? OK, in part because I use X-ray crystallography rather than electron microscopy to look at the structures of interesting biological molecules in my research and the exaggerated claims made on behalf of electron microscopy by the science writers were fist-clenchingly annoying. We scientists are a territorial lot, you know.

I shouldn’t get so worked up because the problem is largely due to the seductive power of the image, something I’ve puzzled over before. All three writers focused on the fact that the new paper reported a picture that you can see; in contrast, although the X-ray method yields a much higher level of detail, its results are produced indirectly through mathematical analysis of the way that molecules scatter an X-ray beam. Dvorsky, Pease and Wild may not have fully grasped that the indirectness of X-ray crystallography in no way diminishes the quality of the information obtained — admittedly not something I would expect a non-specialist to know — but the allure of the image nevertheless seems to have dulled their vision. What frustrated me is that, in spite of having an image served up to them, they didn’t look at it properly, and that allowed errors to creep in.

What is actually new in the paper is that the authors have been able to take a high-contrast image of a DNA fibre (made up of a bundle of DNA double-helices) using electron microscopy. They did this by drying out a drop of DNA dissolved in water over a layer of silicon that had been micro-fabricated to have an array of tiny pillars across its surface. As the water evaporated, strands of DNA were left stretched between the pillars. Because they are suspended above the silicon base, it was possible to get a good image of the DNA fibres (you get poorer contrast if the DNA is lying on a solid surface). In a nice touch, the authors note that their sample preparation is similar to the method used by Wilkins, but they got fibres that were about a thousand times finer than he was able to achieve.

And what do they see? There is certainly some fine structure in the image. There are repetitive features of the size expected for the helical structure in DNA. But it was clear to the Italian researchers and should have been clear to anyone looking at the picture in their online abstract, that the image is not of a single molecule of DNA but a bundle of them. Di Fabrizio and colleagues modelled the structure as a bunch of seven parallel DNA double-helices since that generated a structure with the same thickness as the imaged fibre.

However, is their model correct? If you look at the inset detail in the figure, you see that the indentations on the underside are much deeper than those on the DNA model (middle panel). Perhaps this is an artefact of the way that electron microscopes make images. I don’t know because I am not an expert and the authors don’t comment on the discrepancy.

The bundled nature of the DNA samples prepared for these experiments also helps to explain why the microscopy technique will be unsuitable for analysing the interactions of protein molecules with DNA, contrary to the claims of Dvorsky and Pease. DNA bundles do not occur naturally; in living cells when DNA is being manipulated by proteins — to be copied or used to produce instructions for cellular processes — the double-helix has to be prised apart into separate strands so that the genetic code can be read. We are not likely to be able to investigate these processes using samples composed of tightly packed bundles of DNA double-helices.

Even if a single DNA strand could be isolated and imaged by electron microscopy, the fact that the method relies on largely drying out the sample makes it unsuitable for analysing any proteins bound, since these molecules depend critically on being immersed in water to work properly.

What all this tells you is that Nature is a bitch who likes to make life hard for scientists. Fair play to the Italians who have refined the techniques for preparing DNA fibres to a new level, but it remains to be seen whether their technique will reveal any interesting new biology. I wouldn’t bet on it just yet. Scientists have more work to do, and so too, do science writers.

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Before DNA, before RNA: Life in the hodge-podge world

Take note, DNA and RNA: it’s not all about you. Life on Earth may have began 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.


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.

It differs from RNA and DNA in its sugar backbone: TNA uses threose where RNA uses ribose and DNA deoxyribose. That gives TNA a key advantage, says John Chaput of Arizona State University in Tempe: it is a smaller molecule than ribose or deoxyribose, possibly making TNA easier to form.

Chaput and his colleagues have now created a TNA molecule that folds into a three-dimensional shape and clamps onto a specific protein. These are key steps towards creating a TNA enzyme that can control a chemical reaction, just like RNA.

The team took a library of TNAs and evolved them in the presence of a protein. After three generations, a TNA turned up that had a complex folded shape like an enzyme and could bind to the protein……….

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Life in the Universe by Stephen Hawking

In this talk, I would like to speculate a little, on the development of life in the universe, and in particular, the development of intelligent life. I shall take this to include the human race, even though much of its behaviour through out history, has been pretty stupid, and not calculated to aid the survival of the species. Two questions I shall discuss are, ‘What is the probability of life existing else where in the universe?’ and, ‘How may life develop in the future?’

It is a matter of common experience, that things get more disordered and chaotic with time. This observation can be elevated to the status of a law, the so-called Second Law of Thermodynamics. This says that the total amount of disorder, or entropy, in the universe, always increases with time. However, the Law refers only to the total amount of disorder. The order in one body can increase, provided that the amount of disorder in its surroundings increases by a greater amount. This is what happens in a living being. One can define Life to be an ordered system that can sustain itself against the tendency to disorder, and can reproduce itself. That is, it can make similar, but independent, ordered systems. To do these things, the system must convert energy in some ordered form, like food, sunlight, or electric power, into disordered energy, in the form of heat. A laptopIn this way, the system can satisfy the requirement that the total amount of disorder increases, while, at the same time, increasing the order in itself and its offspring. A living being usually has two elements: a set of instructions that tell the system how to sustain and reproduce itself, and a mechanism to carry out the instructions. In biology, these two parts are called genes and metabolism. But it is worth emphasising that there need be nothing biological about them. For example, a computer virus is a program that will make copies of itself in the memory of a computer, and will transfer itself to other computers. Thus it fits the definition of a living system, that I have given. Like a biological virus, it is a rather degenerate form, because it contains only instructions or genes, and doesn’t have any metabolism of its own. Instead, it reprograms the metabolism of the host computer, or cell. Some people have questioned whether viruses should count as life, because they are parasites, and can not exist independently of their hosts. But then most forms of life, ourselves included, are parasites, in that they feed off and depend for their survival on other forms of life. I think computer viruses should count as life. Maybe it says something about human nature, that the only form of life we have created so far is purely destructive. Talk about creating life in our own image. I shall return to electronic forms of life later on…… Continue reading Life in the Universe by Stephen Hawking

DNA Origami Revolutionizes Metamaterial Manufacture

Physicists use DNA assembly technique to create a ‘metafluid’ capable of manipulating visible light in new ways

Assembly of DNA origami gold particle helices and principle of CD measurements

Back in 2003, the first metamaterial was designed to bend microwaves in ways that ordinary materials can never achieve. The material was made from c-shaped pieces of metal and wires assembled into a kind of honeycomb structure the size of a table top.

Size in is important. The active components in metamaterials and their repeating structure have to be smaller than the wavelength of light they are designed to influence. So the c-shaped pieces of metal–split ring resonators, as physicists call them–were a few millimetres across, big enough to allow the entire structure to be painstakingly assembled by hand.

But that raised an obvious question: how to build similar devices that work for smaller wavelengths….. Continue reading DNA Origami Revolutionizes Metamaterial Manufacture

First life: The search for the first replicator

Life must have begun with a simple molecule that could reproduce itself – and now we think we know how to make one

Dawn of the living

4 BILLION years before present: the surface of a newly formed planet around a medium-sized star is beginning to cool down. It’s a violent place, bombarded by meteorites and riven by volcanic eruptions, with an atmosphere full of toxic gases. But almost as soon as water begins to form pools and oceans on its surface, something extraordinary happens. A molecule, or perhaps a set of molecules, capable of replicating itself arises.

This was the dawn of evolution. Once the first self-replicating entities appeared, natural selection kicked in, favouring any offspring with variations that made them better at replicating themselves. Soon the first simple cells appeared. The rest is prehistory.

Billions of years later, some of the descendants of those first cells evolved into organisms intelligent enough to wonder what their very earliest ancestor was like. What molecule started it all?

As far back as the 1960s, a few of those intelligent organisms began to suspect that the first self-replicating molecules were made of RNA, a close cousin of DNA. This idea has always had a huge problem, though – there was no known way by which RNA molecules could have formed on the primordial Earth. And if RNA molecules couldn’t form spontaneously, how could self-replicating RNA molecules arise? Did some other replicator come first? If so, what was it? The answer is finally beginning to emerge.

When biologists first started to ponder how life arose, the question seemed baffling. In all organisms alive today, the hard work is done by proteins. Proteins can twist and fold into a wild diversity of shapes, so they can do just about anything, including acting as enzymes, substances that catalyse a huge range of chemical reactions. However, the information needed to make proteins is stored in DNA molecules. You can’t make new proteins without DNA, and you can’t make new DNA without proteins. So which came first, proteins or DNA?….. Continue reading First life: The search for the first replicator