First glimpse at the viral birth of DNA

 18 April 2012 by Bob Holmes, Atlanta

 Magazine issue 2861.

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 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). 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."

From issue 2861 of New Scientist magazine, page 10-11.