'Junk DNA' has a purpose, new map of human genome reveals

Vast sections of the human genome that were previously thought to have no useful function and were dismissed as "junk DNA" are in fact involved in key biochemical processes, an international team has found.
The five-year Encyclopedia of DNA Elements, or ENCODE, project has attempted to catalogue the bulk of genetic material that does not fall under the category of protein-coding genes, the building blocks necessary for life that comprise only two per cent of the human genome.
The results of their efforts, published Wednesday in a series of papers in the journals Nature, Genome Research and Genome Biology, are being widely seen as the most significant contribution to understanding the human genome since the last sequence was completed in 2003.

Genes only a tiny part of genome

Genes make up only about two per cent of the human genome and have been well catalogued as part of the Human Genome Project begun in the 1990s, but little has been known about the purpose of the other 98 per cent.

"During the early debates about the Human Genome Project, researchers had predicted that only a few per cent of the human genome sequence encoded proteins, the workhorses of the cell, and that the rest was junk. We now know that this conclusion was wrong," said Eric D. Green, director of the National Human Genome Research Institute in Bethesda, Md., a part of the National Institutes of Health, which funded the ENCODE project to the tune of $288 million since 2003.
"ENCODE has revealed that most of the human genome is involved in the complex molecular choreography required for converting genetic information into living cells and organisms."
The effort to identify the functions of the genetic material that lies between the roughly 20,000 protein-coding genes involved hundreds of scientists at dozens of institutions in the U.S., U.K., Japan, Singapore and Spain.

DNA 'switches' regulate genes

The researchers found that about 80 per cent of the human genome has at least one biochemical activity associated with it. Much of that activity consists of telling protein-coding genes when and where in the body they should turn on and off.
About 18 per cent of DNA is involved in regulating protein-coding genes.
"Every cell in the body has the same genes, but different kinds of cells, such as liver or heart, switch on different combinations of genes," said John A. Stamatoyannopoulos, professor of genome sciences and medicine at the University of Washington who worked on the ENCODE project, in a press release.

"When cells become unhealthy, these combinations change. Understanding how genes turn on and off is therefore vital to deciphering their role in both normal health and disease.
"The instructions for how genes are controlled are contained in small DNA 'switches' that are scattered around the 98 per cent of the genome that does not contain genes. Mapping and decoding these instructions is a central mission of the ENCODE project."
The researchers located more than four million of these DNA 'switches,' information that should help scientists better understand how to prevent, diagnose and treat disease.
To help them understand the relationship between disease-associated genetic changes and the gene-controlling switches scattered around the genome, the researchers collected DNA maps from 349 tissue samples covering all major organ systems in adults and all stages of human development and compared them against genetic studies of more than 400 common diseases and clinical traits.
"They found that most disease-associated genetic changes occurred within gene-regulating switches, often located far away from the genes they control," a University of Washington press release said. "Most changes affected circuits active during early human development, when body tissues are most vulnerable."

Database publicly available online

The ENCODE scientists made their data publicly available in a vast database that has been posted on the ENCODE project portal as well as on the websites of the University of California, Santa Cruz Genome Browser, the National Center for Biotechnology Information, and the European Bioinformatics Institute.

'The ENCODE catalogue is like Google Maps for the human genome.'— Elise Feingold, National Human Genome Research Institute

The journal Nature diverged from its usual practice and presented the findings of the six core papers published by the ENCODE consortium as a series of thematic threads accessible through an interactive online "ENCODE Explorer."
Another 24 associated papers that came out of the research appeared in the journals Genome Research and Genome Biology.
"The ENCODE catalogue is like Google Maps for the human genome," said Elise Feingold, a program director at the National Human Genome Research Institute who helped start the ENCODE Project, in a news release.
"Simply by selecting the magnification in Google Maps, you can see countries, states, cities, streets, even individual intersections, and by selecting different features, you can get directions, see street names and photos, and get information about traffic and even weather.
"The ENCODE maps allow researchers to inspect the chromosomes, genes, functional elements and individual nucleotides in the human genome in much the same way."

Scientific explanation of psychopathy cuts jail time

Serial sex offender Raymond Henry Garland, considered one of Australia's most dangerous sexual predators, was officially diagnosed a psychopath last week. Psychiatrist Joan Lawrence told the Brisbane District Court that Garland had an "almost 100 per cent chance of violent reoffending." Garland has been dealt four indefinite sentences – but research out today suggests that biological evidence of psychopathy could alter the length of such sentences.

Brain scans and genetic tests are becoming a common feature of courtroom battles, as biological evidence is increasingly used to explain a person's criminal behaviour. For example, last year an Italian woman convicted of murdering her sister had her lifetime sentence reduced to 20 years on the basis of brain and genetic tests, which provided biological explanations for her aggressive behaviour.

But does the inclusion of such evidence affect the sentencing of psychopaths – people with a disorder currently thought to be untreatable? Any evidence could act as a double-edged sword, says James Tabery at the University of Utah. A so-called biomechanism to explain psychopathic behaviour could be used to argue that a person is less culpable for their actions, reducing their sentence. On the other hand, the defendant could be seen as more likely to reoffend and receive a longer sentence.

Testing the sword

To find out "which way the sword was going to cut", Tabery, together with psychologist Lisa Aspinwall and law professor Teneille Brown, also at Utah, sent out a survey to 181 US judges based in a number of different states.

Each judge was asked to sentence a convicted criminal diagnosed as a psychopath. The team's fictional character was based on Stephen Mobley, who robbed and then killed a Domino's pizza store manager in 1991. Mobley went on to brag about the crime, and even got the word "Domino" tattooed on his back. Psychologists claimed that his behaviour and lack of remorse was psychopathic and untreatable. At the time, Mobley's request to submit a genetic-based defence for his behaviour was denied, says Tabery. "The Georgia State Supreme Court said [genetic evidence] wouldn't have made any difference," he says. "He was sentenced to death."

In Tabery's fictional case, a man was found guilty of the similar crime of aggravated battery, although the victim was not killed but left with permanent brain damage. The criminal was diagnosed as a psychopath by a psychiatrist. Half of the judges were given additional evidence from a second psychiatrist, who said that the man's behaviour was the result of a genetic mutation that caused a structural abnormality in his brain. Half of each group of judges received the diagnosis as a form of defence, pleading the man's lack of control and culpability over his actions. The other judges saw the diagnosis as part of a prosecution which argued that the man was likely to reoffend.

Shorter sentences

Without a diagnosis, the judges surveyed said they would have given the man a sentence of about nine years. Once he had been diagnosed as an untreatable psychopath, however, the average sentence jumped to 14 years. When judges were presented with biological evidence of the genetic mutation, this sentence was lowered to around 13 years, regardless of whether the evidence was presented by the prosecution or defence.

"We saw both sides of the double-edged sword in play," says Tabery. "The addition of a biological mechanism slightly reduces the sentence compared to just the diagnosis of psychopathy, but it's still significantly higher than what judges said their average sentences are for aggravated battery."

Stephen Morse, professor of law and psychiatry at the University of Pennsylvania in Philadelphia, says that the issue of free will in responsibility for one's actions should be "beside the point" in a court room. "Having free will or not having it is not part of any legal doctrine, and needs never be proven or disproven."

But if biological evidence can swing sentences, should all psychopaths be given the option to include brain scans and genetic tests in their defence? Or should the use of such evidence be ruled out entirely? "Different states and different judges vary in how they process this information," says Tabery.

Morse thinks this variation is a real problem in the criminal justice system. "It's usually up to the judge to decide what factors to balance at sentence, how they should be weighed and what evidence to consider, and that results in very varied sentencing," he says. "I think there should be less discretion involved in sentencing, although judges hate the idea."

Journal reference: Science, DOI: 10.1126/science.1219569

Gaze-tracking illusion lets you draw with your eyes

IMAGINE drawing or writing on a screen with just your eyes. That's what a novel gaze-tracking software promises to do for people with locked-in syndrome.

Existing eye-writing systems involve focusing on a letter then blinking to select it. Moving your eyes smoothly enough to trace out words is hard because your eyes constantly make jerky motions known as saccades, unless you are tracking a moving object.

Jean Lorenceau at the Pierre and Marie Curie University in Paris, France, has found a way to fool your eyes into making smooth movements by using an optical illusion called "reverse phi motion".

Phi motion is the effect that turns a series of still photos into a movie, but reverse phi motion is weirder. Take a film of a moving white dot then turn the dot in every other frame black. The film will appear to run backwards. Lorenceau's system manipulates the illusion to trick you into thinking you are moving a dot around the screen with your eyes, so the motion is smooth. A gaze-tracking camera follows the right eye's movements to control a cursor on the screen. This lets you trace out numbers, letters or drawings. "It's like surfing, you move your eyes to get on the wave and once you're on you just slide with it," Lorenceau says.

Is this Richard III, England's last Plantagenet king?

What exactly has been found?
The body of an adult male has been excavated from what is believed to be ruins of the choir area of the Grey Friars church in Leicester. It's now a car park in the city centre, but was used as a church in the late 15th century. Some records suggest that Richard III, the last Plantagenet king of England, was buried here.

So how do we know it's him? Has the body got a hunched back?
We don't know it's him – yet – but yes, the skeleton does show signs of spinal curvature. Contemporary accounts, reinforced later by Shakespeare, described Richard III as being "hunchbacked". The newly found body appears to have scoliosis, a form of spinal curvature that would have made the man's right shoulder appear higher than the left shoulder. The classic "hunchback" is caused by kyphosis but there is no evidence of this in the Leicester skeleton.

Any other evidence?
Yes. The man who became this skeleton took a beating. He has a small penetrating wound to the top of the head, and a much larger wound where a slice has been cut off the skull at the side and back – consistent with the swing of a blade. On 22 August 1485, Richard III was killed at the Battle of Bosworth Field by blows that some accounts describe as being so violent they drove his helmet into his head.

The Leicester skeleton also has a barbed iron arrowhead stuck in its upper back. But the middle ages were violent times, so again this is only supporting evidence.

Can DNA testing determine if the body is Richard III?
Perhaps. The Richard III Society says it has located someone – Londoner Michael Ibsen – who is apparently the 17th great grand-nephew of Richard III, in the female line. Ibsen's late mother Joy Ibsen is purportedly a direct descendent of the King's eldest sister, Anne. Richard's male relatives were executed.

Leicester University geneticists hope to extract mitochondrial DNA taken from the skeleton's teeth and compare it with DNA from Ibsen. Mitochondrial DNA is transmitted only through the female line, so if Ibsen really is a direct descendent, his mtDNA can be compared with that from the skeleton.

Mitochondrial DNA is present in thousands of copies per cell, so is easier to extract from degraded tissue than nuclear DNA, which is only present in one copy, in the nucleus. MtDNA was used, for example, to identify the remains of Jesse James, the 19th century American outlaw. But in that case, the living maternal relatives were a great grandson and great-great grandson. With Richard III, many more generations have passed, so the challenges are that much greater.

How can we be sure Joy Ibsen is a direct descendent?
This is one of the shakiest parts of the project, relying as it does on historical records stretching back hundreds of years. The family tree linking Ibsen with Richard III's sister was made by historian John Ashdown-Hill. Kevin Schürer at Leicester University is leading the team assessing the historical evidence to try and corroborate Ibsen's genealogy.

"It's prudent to have a second set of eyes go over the tree and to use other historical data to try and verify it," says geneticist Turi King at Leicester University, who is working on extracting the ancient DNA. Until we know how much mtDNA we can get out of the skeleton, we won't know whether we can say if it is related to Michael Ibsen or not.