10 | NewScientist | 21 April 2012

EARLY life underwent a massive system upgrade around 4 billion years ago. DNA’s simple code can encrypt a huge amount of information and its trademark double helix makes it remarkably stable. But most biologists agree that life began with a soup of RNA, a less stable genetic molecule. So at some point the vast majority of life must have switched its code.

For the first time, biologists have had a glimpse at how this may have happened. The rare insight points to archaic viruses as the inventors of DNA. Better yet, the process that enabled the ancient upgrade occasionally still happens today.

According to the prevailing dogma, the earliest life forms arose from a loose mix of proteins and nucleic acids that used RNA as their genetic material. At some point, most of life began storing genetic information in DNA; all the cellular life we know today, and most modern viruses as well, are DNA-based. The switch created a problem familiar to anyone who has upgraded their laptop to a new operating system: how do

you port over your old software to the new platform? The genes of RNA life contained solutions to many of the challenges of existence, but because RNA cannot combine with DNA there was no obvious way for the new DNA life to use this information.

The discovery of an unusual hybrid virus living in one of the harshest environments on the planet suggests a solution. Ken Stedman, of Portland State University in Oregon, stumbled on it by accident while studying the microbes that live in a hot, acidic lake in California’s Lassen Volcanic National Park. He filtered all the virus-sized particles from 40 litres of lake water, and randomly sequenced some 400,000 pieces of viral DNA to see what was there.

He found something odd: a gene, made of DNA, that looked like the gene for a protein coat from an RNA virus. Some viruses, called retroviruses, have a reverse transcriptase enzyme to translate RNA into DNA, but this gene did not come from a retrovirus. So how had the gene leapt from RNA to DNA?

Intrigued, Stedman’s student,

Geoff Diemer, produced a full sequence of the strange virus’s genome. He found that alongside the RNA-derived gene it contained a gene for DNA replication typical of a DNA virus.

Finding these two genes in one organism was a bit like finding a sunflower gene in a chimpanzee, except that plants and animals probably share a much more recent common ancestor than DNA and RNA viruses, which are thought to have diverged billions of years ago. “Our first thought was that we messed up somehow,” says Stedman.

They re-sequenced the entire viral genome but the two genes

were still there, Diemer reported this week at NASA’s Astrobiology Science conference in Atlanta, Georgia. The work will appear in Biology Direct.

To see whether this motley virus was just a one-off, Stedman and Diemer scanned databases of viral DNA sequences. They found that something very similar had turned up in samples of ocean water sequenced by a team led by Craig Venter, of the J Craig Venter Institute. “These hybrid viruses are present not just in this acidic hot lake, but

Bob Holmes, Atlanta

First glimpse at the birth of DNA W

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in at least a couple of oceanic samples, and probably other places as well,” says Stedman.

The find proves that modern viruses can combine information coded in the two normally separate genetic molecules. And it lends support to the idea that it was viruses that performed the upgrade from RNA and effectively gave rise to DNA.

Stedman and Diemer’s hybrid virus is not a living fossil – a left-over that has stuck around since the dawn of life. Its genes are similar to their parent genes in RNA and DNA viruses, and the team estimates that it hybridised within the last 10 million years.

Stedman suggests that it may have formed when an RNA virus, DNA virus and retrovirus all infected a cell at the same time. This perfect viral storm could have triggered a three-way genetic mash-up (see diagram, left).

“It was a bit like finding a sunflower gene in a chimp, except plants and animals have more in common”

Not lost in translationAround 4 billion years ago, most life swapped RNA genes for DNA genes, but how?

A modern hybrid virus shows that RNA information can transfer to DNA inside a cell. A similar non-cellular process could have taken place 4 billion years ago

VIRUS WORLD

CELLULAR LIFE

DNA viruses RNA viruses retroviruses

MODERN VIRUSESReverse transcriptase makes a DNA copy of an RNA gene and inserts it into the DNA genome

PREBIOTIC RNA

WORLD

HYBRID DNA VIRUS

DNA virus genome

DNA copy of gene from RNA virus

RNA DNA

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21 April 2012 | NewScientist | 11

–Hybrids within–

WHEN surgeons tackle a tumour in the body, they can usually afford to remove potentially healthy tissue from around the cancerous mass to make sure they get rid of every harmful cell. In the brain they don’t have this luxury – healthy cells are too important to lose. Gold nanoparticles may now give surgeons the clearest view yet of cancerous cells during an operation, helping them to remove tumour cells without harming their healthy neighbours.

Surgeons regularly use magnetic resonance imaging to guide brain surgery. However, some cancerous cells – unseen by MRI or the naked eye – can be left behind. To overcome this problem, Sanjiv Gambhir at Stanford University in California and colleagues have developed spherical nanoparticles with properties that help surgeons detect cancerous cells in three different ways.

The particles consist of a gold core coated with a metal called gadolinium and a layer of silica. Gambhir’s team showed that, when injected into the bloodstream, the nanoparticles can cross the blood-brain barrier and accumulate in cancer cells without needing a specific targeting mechanism. That is because blood vessels in cancerous tissue are leakier than healthy vessels. This allows the nanoparticles to spill through and lodge themselves in the

surrounding cancerous tissue.To test their ability to highlight

tumours, the team first injected the nanoparticles into the tails of mice whose brains contained cancer cells. The cells were taken from people with glioblastomas – the most aggressive form of brain tumour that grows tiny, finger-like projections.

The team then used MRI to locate the tumours and determine their shape. The dark gadolinium aided this visualisation, defining tumour boundaries. The team then directed a pulsed laser at the brain, which heated the nanoparticles’ gold cores, causing them to vibrate. The vibrations emit a noise signal which can be picked up by a sonogram to produce real-time images of the tumour. Finally, after removing the majority of the cancerous mass, the team visualised the remaining tissue using a Raman spectroscope. Interaction of the spectroscope’s photon beam with the silica highlighted any last cancerous cells (Nature Medicine, DOI: 10.1038/nm.2721).

Gambhir is about to test similar nanoparticles in people with colorectal cancer, and is hopeful that the results will help speed the use of the nanoparticles in brain cancer. He also hopes to develop a way to heat the gold so that the particles not only highlight cancer cells, but kill them at the same time. Sara Reardon n

Gold nanoparticles reveal tumours in three ways

For daily news stories, visit newscientist.com/news

The retrovirus used its reverse transcriptase enzymes to mistakenly make a DNA copy of an RNA virus gene, which combined with the DNA virus’s genome to yield the unlikely hybrid. A few earlier studies had hinted that such viral super-hybrids could exist, but Stedman’s study is the first to show it directly.

“These are two lineages that we never think of as overlapping,” says virologist Luis Villarreal of the University of California at Irvine. The lack of respect for species boundaries echoes what many biologists suspect the original virus world must have been like around the birth of DNA 4 billion years ago, he says.

The parallel with the ancient virus world is not perfect, since the modern viruses’ life cycles are very different from those of their ancestors. The primordial virus world was a non-cellular stage in

the evolution of life, the details of which are very obscure, says Eugene Koonin, an evolutionary genomicist at the National Center for Biotechnology Information in Bethesda, Maryland. “Nowadays, viruses replicate exclusively within cells.”

Still, the finding proves that a community of viruses can move information from RNA into DNA – and that modern DNA viruses do have access to genes evolved by those in the very separate world of RNA viruses. This bolsters the argument that a similar transfer happened during early life’s RNA-to-DNA transition.

It also tells us that our modern world retains at least a trace of the uninhibited genetic free-for-all that must have preceded our current staid, cellular existence. Or as Koonin puts it: “The virus world, in its diversity and unpredictability, is still with us.” n –Wanted: every last cancer cell–

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