The Alan Sondheim Mail Archive

January 18, 2010


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From: <moderator@portside.org>
Date: Mon, Jan 18, 2010 at 12:04 AM
Subject: Hunting Fossil Viruses in Human DNA
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Hunting Fossil Viruses in Human DNA
By CARL ZIMMER
New York Times
January 12, 2010
http://www.nytimes.com/2010/01/12/science/12paleo.html

The borna virus is at once obscure and grotesque. It can
infect mammals and birds, but scientists know little
about its effects on its victims. In some species it
seems to be harmless, but it can drive horses into wild
fits. The horses sometimes kill themselves by smashing
in their skulls. In other cases, they starve themselves
to death. Some scientists have even claimed that borna
viruses alter human behavior, playing a role in
schizophrenia and bipolar disorder, although others say
there is no solid evidence of a link.

The virus now turns out to have an intimate bond with
every person on Earth. In the latest issue of Nature, a
team of Japanese and American scientists report that the
human genome contains borna virus genes. The virus
infected our monkey-like ancestors 40 million years ago,
and its genes have been passed down ever since.

Borna viruses are not the only viruses lurking in our
genome. Scientists have found about 100,000 elements of
human DNA that probably came from viruses. But the borna
virus belongs to a kind of virus that has never been
found in the human genome before. Its discovery raises
the possibility that many more viruses are left to be
found.

Scientists who hunt for these viruses think of
themselves as paleontologists searching for fossils.
Just as animals get buried in rock, these viruses become
trapped in the genomes of their hosts. While their free-
living relatives continue to evolve, fossil viruses are
effectively frozen in time.

"We can really dig fossils out of the genome and
literally put them back together," said C�dric
Feschotte, a genome biologist at the University of
Texas, Arlington. "It's like putting a hominid back
together and asking it if it can walk upright."

When scientists sequenced the human genome in 2001, they
noticed many segments that bore a striking resemblance
to genes in retroviruses, a class of viruses that
includes H.I.V.

Retroviruses carry their genetic material in a single-
stranded version of DNA, called RNA. To make new
viruses, they make DNA versions of their genes, which
are inserted into a host cell's genome. The cell then
reads the retrovirus's genes as if they were its own,
and manufactures new retroviruses.

Scientists speculated that every now and then a
retrovirus inserted itself into a host cell and then
failed to turn it into a virus factory. If the trapped
retrovirus happened to be in sperm or egg cells, its DNA
might be passed down to the host's descendants. From
generation to generation, the virus's DNA would mutate.
It would lose its ability to produce normal viruses. For
a while it might be able to make new viruses that could
re-infect the same cell, but over enough time, the
viruses would become disabled.

In recent years, scientists have found several lines of
evidence to support this idea. . Koala retroviruses, for
example, appear to be in the middle of the journey. The
viruses can move from one koala to another. But in some
populations of koalas, the virus's DNA is permanently
lodged in their genomes.

Thierry Heidmann of the Gustave Roussy Institute in
France and his colleagues put the fossil virus
hypothesis to a spectacular test: they tried to
resurrect a dead retrovirus. They first identified a
number of copies of the same virus-like stretch of DNA
in the human genome. Each version had its own set of
mutations that it acquired after the virus had invaded
our ancestors.

By comparing the copies, Dr. Heidmann and his colleagues
were able to figure out what the original sequence of
the virus's genes had been. When they synthesized the
genes from scratch and injected the genetic material
into cells, the cells produced new viruses.

"It was a tour-de-force of an experiment," said John
Coffin, an expert on fossil viruses at Tufts University.

Now fossil virus hunters are moving beyond the human
genome. They're taking advantage of the growing number
of mammal genomes piling up in online databases and
helping to flesh out the evolutionary history of
viruses, reaching back tens of millions of years. Aris
Katzourakis, an evolutionary biologist at the University
of Oxford, and his colleagues recently went on a hunt
for fossils of foamy viruses in mammals. Foamy viruses
infect some mammals, including monkeys and apes. Primate
foamy viruses can infect humans harmlessly, but
researchers fear they may evolve to become dangerous.
Dr. Katzourakis and his colleagues discovered hundreds
of foamy virus copies in the DNA of the two-toed sloth.
They then found the same virus lurking in the genome of
the three-toed sloth. Before Dr. Katzourakis's fossil
hunt, scientists had never found a foamy virus infecting
any sloths, or any of their relatives like armadillos
and anteaters.

Sloths and their relatives branched off from all other
placental mammals about 100 million years ago. Dr.
Katzourakis's discovery thus reveals the great antiquity
of foamy viruses. They were already infecting the common
ancestor of all placental mammals back when dinosaurs
ruled the Earth.

These fossils are also offering clues to how viruses
evolved. Dr. Katzourakis and his colleagues have found
fossil viruses that are helping shed light on the deep
history of H.I.V., for example.

H.I.V. evolved about a century ago from a chimpanzee
virus known as simian immunodeficiency virus, or S.I.V.
Many apes and monkeys carry their own strain of S.I.V,
but it's not clear how long the viruses have been
infecting primates.

In 2008, Dr. Katzourakis and his colleagues discovered
fossil S.I.V. in the genome of the gray lemur, a primate
that lives in Madagascar. Last May, Dr. Feschotte and
his colleagues reported that they had found the same
fossil virus in the fat-tailed lemur.

Scientists had never before found S.I.V. in lemurs,
which branched off from all other living primates some
50 million years ago. The fossil virus is also missing
one of the genes found in all other forms of S.I.V. and
H.I.V. It may be a transitional form of the virus, akin
to the fossils paleontologists have found of feathered
dinosaurs that couldn't fly.

Fossil viruses are also illuminating human evolution.
Scientists estimate that 8.3 percent of the human genome
can be traced back to retrovirus infections. To put that
in perspective, that's seven times more DNA than is
found in all the 20,000 protein-coding genes in the
human genome.

But that figure may be too low, according to Dr.
Katzourakis. "The measurable diversity of viruses may go
up, and the true diversity may be much higher," he said.

For one thing, some viruses may be too well hidden for
scientists to see. The discovery of borna viruses in the
human genome is another reason to wonder if we're
actually more viral than we know. All fossil viruses
discovered until now have been retroviruses, but borna
viruses are not.

Unlike retroviruses, borna viruses do not insert
themselves into host genomes. Instead, they take up
residence inside the nucleus, the chamber that holds our
DNA. There, they manipulate the cell's proteins to make
new copies of themselves.

Keizo Tomonaga, a virologist at Osaka University,
discovered the borna virus DNA by accident. He had been
comparing the virus genes with human genes to see if the
virus might have evolved to mimic our own proteins.
Instead, he discovered four segments of human DNA that
clearly had descended from a borna virus gene. "I was
surprised when I found them," Dr. Tomonaga said.

He and his colleagues found the same borna virus DNA in
apes and monkeys. In other words, borna virus first
invaded the common ancestor of humans, apes and monkeys
about 40 million years ago. But primates were not the
only targets for borna viruses. Dr. Tomonaga and his
colleagues have found independent invasions in other
mammals, including ground squirrels, guinea pigs and
elephants.

Dr. Tomonaga and his colleagues suspect that borna
viruses didn't actually invade mammal genomes. Instead,
the genomes kidnapped them.

Mammal genomes contain thousands of stretches of DNA
called LINEs. LINEs sometimes make copies of themselves
that get reinserted back into the genome. Dr. Tomonaga's
research indicates that LINEs grabbed the genes of borna
viruses and pulled them into their genome.

The discovery raises the possibility that LINEs have
kidnapped other viruses floating near their host's DNA,
like flu viruses.

Two of the four copies of the borna virus gene carry
crippling mutations. It's impossible for our cells to
make proteins from them. But the other two genes look
remarkably intact, perhaps suggesting that our bodies
use them for our own benefit. Exactly what they do isn't
clear though.

Studies on other captive viruses have revealed that some
help ward off viral invasions. One virus protein,
syncytin, is essential for our being born at all.

"The only place it's expressed is in the placenta," Dr.
Heidmann said. To understand its function, he and his
colleagues disabled the gene in mice. Without syncytin,
mice developed deformed placentas, and their embryos
died.

Syncytin started as a surface protein on retroviruses
that fused them to cells. When mammals captured the
gene, they used it in the placenta to create a layer of
fused cells through which mothers can send nutrients to
their embryos.

Dr. Heidmann and his colleagues have discovered that
over the past 100 million years, mammals have repeatedly
harnessed viruses to make syncytin. "Wherever we search
for them, we find them," Dr. Heidmann said.

But the syncytin genes we use today may have actually
replaced an ancestral one that a virus bequeathed to the
very first placental mammals. In fact, that infection
may have made the placenta possible in the first place.
"It was a major event for animal evolution," Dr.
Heidmann said.

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