Best evidence yet that a single gene can affect IQ

A massive genetics study relying on MRI brain scans and DNA samples from over 20,000 people has revealed what is claimed as the biggest effect yet of a single gene on intelligence – although the effect is small.

There is little dispute that genetics accounts for a large amount of the variation in people's intelligence, but studies have consistently failed to find any single genes that have a substantial impact. Instead, researchers typically find that hundreds of genes contribute.

Following a brain study on an unprecedented scale, an international collaboration has now managed to tease out a single gene that does have a measurable effect on intelligence. But the effect – although measurable – is small: the gene alters IQ by just 1.29 points. According to some researchers, that essentially proves that intelligence relies on the action of a multitude of genes after all.

"It seems like the biggest single-gene impact we know of that affects IQ," says Paul Thompson of the University of California, Los Angeles, who led the collaboration of 207 researchers. "But it's not a massive effect on IQ overall," he says.

Two teaspoons

The variant is in a gene called HMGA2, which has previously been linked with people's height. At the site of the relevant mutation, the IQ difference depends on a change of a single DNA "letter" from C, standing for cytosine, to T, standing for thymine.

"C is the good one," says Thompson. As well as raising IQ by 1.29, it increases the overall volume of the brain – but only by 0.58 per cent of average brain size, adding around 9 cubic centimetres of tissue. "It's a loss or gain of about 2 teaspoons," says Thompson.

The brain-size-altering effect of the gene is what led the researchers to study the impact on IQ. In their study, involving 21,151 adult subjects, they took DNA samples but also scanned each volunteer's brain, specifically looking for size differences either in the brain overall or in specific parts of it, such as the hippocampus, thought to be the seat of memory and learning.

Our genes account for a big chunk of the variability in intelligence, but no individual genes can take much credit for human smarts

C-ing double

After the researchers had established that HMGA2 affected overall brain size, they looked in more detail at a subset of 1642 volunteers from a twin study in Brisbane, Australia, who had all taken standard IQ tests. From that analysis, they were then able to measure the effect of the C on IQ. When people inherit C-variants from both parents they enjoy double the effect: a rise in IQ of about 2.6.

"It's important they've found this gene, but it took a sample of 20,000 people to find it, precisely because the effect is so small," says Robert Plomin at the Institute of Psychiatry in London, and lead author of a groundbreaking study in 2007 which failed to find any single genes of disproportionate importance in intelligence. "If it's this hard to find an effect of just 1 per cent, what you're really showing is that the 'cup' is 99-per-cent empty," he says.

Steven Pinker, an author and professor of neuropsychology at Harvard University, agrees. "It's an important finding, assuming it holds up," he says. Pinker says that the findings are a first step in demonstrating that intelligence relies on large numbers of genes, each with a tiny effect, rather than on single genes that have moderate or large effects, but which are so rare that none has yet been identified.

Brain ager

The other key finding by Thompson's team was that a variant of a gene called TESC affects the size of the hippocampus, altering its size by 1.2 per cent above or below the average.

Thompson says that in adulthood, the hippocampus shrinks by about 0.5 per cent per year, so having the "wrong" gene variant can equate to more than two years of ageing, and having two copies of it is equivalent to five years of ageing – all of which could hasten the arrival of dementia or other diseases related to hippocampus shrinkage, including Alzheimer's disease and depression.

LHC gets first glimpse of excited baryon

Another day, another particle. Unlike the Higgs boson, the neutral Xi_b baryon is not expected to solve any deep, outstanding mysteries. But, sightings of its excited state are another first for the Large Hadron Collider (LHC) at CERN near Geneva, Switzerland.

The Xi_b, a conglomerate of quarks, was previously seen by the now-defunct Tevatron collider at Fermilab in Batavia, Illinois, but only in its lowest energy state.

Theory says the particle has higher energy states that decay rapidly into a zoo of lower-mass muons, pions and protons. These are tough to spot in the LHC's particle detritus but can be used to confirm the presence of excited Xi_bs.

The team at CMS, one of the LHC's two main detectors, now reports piecing together 21 instances of excited Xi_b baryons. The result has a statistical significance greater than 5 sigma, meaning there is less than 1-in-a-million chance that it's a fluke.

"The significance is that you are able to find these states in the very complicated environment of the LHC," says CMS's Nicholas Hadley.

"It fills in another little hole where there was a 'hasn't been seen yet' in the drawing of predicted things," he says.

World's most sensitive scales detect a yoctogram

How do you weigh an atom down to the last proton? With scales accurate enough to measure the smallest unit of mass, aka the yoctogram, which is just one septillionth of a gram.

No ordinary scales will do ‐ the tiniest weights are measured using nanotubes, which vibrate at different frequencies depending on the mass of the particles or molecules on them. Until now, 100 yoctograms ‐ or a tenth of a zeptogram ‐ was the smallest mass the most sensitive sensor could detect.

To go even lower, Adrian Bachtold and his colleagues at the Catalan Institute of Nanotechnology in Barcelona, Spain, used short nanotubes. They give the best resolution and work at the low temperatures thought best for measuring frequency. Although the equipment was placed in a vacuum to minimise interference from other atoms, Bachtold removed any stray atoms by temporarily turning up the heat on the tubes to disrupt any bonds to atoms.

Then the sensor was able to weigh an atom of xenon to the nearest yoctogram, or 10^-24 grams. This makes it the first scale capable of detecting a single proton, which weighs in at 1.7 yoctograms.

"The yoctogram mass sensitivity achieved by the Catalan team is certainly spectacular ‐ the challenge ahead will be to routinely manufacture nanotube sensors at low cost," says Rachel McKendry, a nanoscientist at University College London.

Bachtold hopes the scales could be used to distinguish different elements in chemical samples, which might differ only by a few protons. They might also diagnose health conditions by identifying proton-scale differences in molecular mass that are markers of disease.

Lightning directed by laser beams

IT'S not quite Zeus, but at least it's not entirely myth. Lasers have been used for the first time to trigger and divert lightning bolts.

The idea of using a powerful laser to create a low-resistance path through the atmosphere - a virtual lightning rod - gained momentum in the 1990s. Lasers were developed that could generate terawatts (trillions of watts) of power for femtoseconds (millionths of billionths of a second). These created pulses so intense that they ripped electrons from air molecules, forming channels of ionised air along the beam path. These paths focused the laser light in high intensity zones called filaments, which kept the air ionised long after the laser passed through, but failed to trigger or direct lightning.

In 2008, a group led by André Mysyrowicz of the applied optics laboratory at ENSTA ParisTech in France took a trailer-sized laser to New Mexico for field experiments with clouds. The group found that its laser filaments increased electrical activity in storm clouds, but did not trigger lightning.

Now the group has reached two milestones on the road to practical lightning protection with a more compact laser. In one experiment in a military lab in Toulouse, France, they set up a high-voltage discharge with two possible targets about 2.5 metres away. With the laser off, the artificial lightning always hit the closer target. But with the laser on, generating a filament path to the farther target, the discharge went where it was directed.

In a second experiment, Mysyrowicz's team aimed the laser beam across 50 metres of a lab, passing 5 to 20 centimetres from a lightning-producing electrode and an oppositely charged electrode. Usually, lightning jumps straight from electrode to electrode, but with the laser on, the discharge jumped to the laser filament and followed it before jumping to the second electrode (AIP Advances, DOI: 10.1063/1.3690961).

Controlling the lightning without making contact with the electrodes makes this more like a real-world situation, says Jérôme Kasparian of the University of Geneva, Switzerland. "In the clouds you don't really have an electrode you can touch," he says. But in the real world, he adds, the targets are far more distant.

Move over DNA: Six new molecules can carry genes

All of a sudden, DNA has no reason to feel special. For decades it seemed that only a handful of molecules could store genetic information and pass it on. But now synthetic biologists have discovered that six others can pull off the same trick, and there may be many more to find.

The ability to copy information from one molecule to another is fundamental to all life. Organisms pass their genes to their descendants, often with small changes, and as a result life can evolve over the generations. Barring a few exceptions, all known organisms use DNA as the information carrier.

A host of alternative nucleic acids have been made in labs over the years, but no one has made them work like DNA.

This problem has now been cracked. "This unique ability of DNA and RNA to encode information can be implemented in other backbones," says Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK.

"Everyone thought we were limited to RNA and DNA," says John Sutherland of the MRC Laboratory of Molecular Biology in Cambridge, UK, who was not involved in the study. "This paper is a game-changer."

Evolving XNA

Holliger's team focused on six XNAs (xeno-nucleic acids). DNA and RNA are made of a sugar, a phosphate and a base. The XNAs had different sugars, and in some of them the sugars are replaced with completely different molecules.

A key hurdle for the team was to create enzymes that could copy a gene from a DNA molecule to an XNA molecule, and other enzymes that could copy it back into DNA.

They started with enzymes that do this in DNA only. Over the years the team made incremental tweaks until they produced enzymes that could work on XNAs.

Once they had created these enzymes, they were able to store information in each of the XNAs, copy it to DNA, and copy it back into a new XNA. In effect, the first XNA passed its information on to the new one – albeit in a roundabout way. "The cycle we have is a bit like a retrovirus, which cycles between RNA and DNA," Holliger says.

This is the first time artificial molecules have been made to pass genes on to their descendants. Because the XNAs can do this, they are capable of evolution.

"The immediate question is whether these XNAs can be introduced into cells," says Farren Isaacs of Yale University in New Haven, Connecticut. Once the XNAs were installed, they could replicate and evolve on their own. "That would be remarkable."

Journal reference: Science DOI: 10.1126/science.1217622

Origin of life

The finding is a proof of principle that life needn't be based on DNA and RNA. Astrobiologists have long suspected as much.
"This is very interesting with respect to the origin of life," says Jack Szostak of Harvard University in Boston, Massachusetts. Nowadays, all life-forms use either DNA or RNA to store genetic information. Many biologists suspect that the first life-forms used RNA, and DNA was adopted later. But we don't know why those two molecules were chosen: are they the best possible storage media, or were they simply the only things available?
Holliger suspects RNA was an opportunistic choice. "Clearly, there is no overwhelming functional imperative to use DNA and RNA," he says. Instead, life may have started with RNA simply because it was made in large quantities on the early Earth.
Most biologists think life on Earth began with RNA because it can both store information and catalyse useful reactions. In his latest experiment, Holliger has now shown that one of his XNA's – 1,5-anhydrohexitol nucleic acid, or HNA – can fold into a 3D shape and bind to specific target molecules. This is the first step in becoming an enzyme. The same thing had previously been done for threose nucleic acid (TNA).
This suggests XNAs might form the basis of life on other planets, where different environments led to different chemistry. "I would be surprised if we find truly extraterrestrial life that was based on DNA and RNA," Holliger says. "There might have been an XNA-world on a different planet."

Facebook shares are overvalued, say financial analysts

Want a piece of Facebook? The social networking behemoth has finally announced that it is going public – on 18 May – and its proposed share price values the company at between $77 billion and $96 billion. "Econophysicists", however, say the company will be subject to a stock price bubble and is vastly overvalued.

Peter Cauwels and Didier Sornette, entrepreneurial risk analysts at the Swiss Federal Institute of Technology Zurich, say that financial institutions do not publish the methods they use for valuing social networking companies. So Cauwels and Sornette developed their own model, which they have made publicly available (arxiv.org/abs/1110.1319).

The model suggests that even with the most optimistic growth forecasts, Facebook's fundamental value is no more than $30 billion. Cauwels says that the company's unique status as the biggest social networking start-up gives it extra potential, worth perhaps another $30 billion. "Investors should be aware that everything they pay above $30 billion is just an option on future potential and everything above $60 billion is bubble money," he says.

Much of the excitement is based on Facebook's meteoric rise – the company has gained new users at an exponential rate since its launch in 2004. But Sornette and Cauwels say there are signs that its growth is slowing, and that the next generation is starting to think that Facebook is boring. "It's something their parents are using," says Cauwels.