Central dogma of genetics maybe not so central

In thousands of genes, RNA is not a faithful copy of DNA By Tina Hesman Saey

Web edition : Thursday, November 4th, 2010

   Text Siz e

WASHINGTON — Text messagers and computer gamers aren’t alone in the willful misspelling
department. RNA molecules do it too.

RNA molecules aren’t always faithful reproductions of the genetic instructions contained within DNA, a
new study shows. The finding seems to violate a tenet of genetics so fundamental that scientists call it
the central dogma: DNA letters encode information and RNA is made in DNA’s likeness. The RNA then
serves as a template to build proteins.

But a study of RNA in white blood cells from 27 different people shows that, on average, each person
has nearly 4,000 genes in which the RNA copies contain misspellings not found in DNA.

“It’s unbelievable,” says Mingyao Li, a geneticist at the University of Pennsylvania Medical School in
Philadelphia. Li presented the finding November 3 in Washington, D.C., at the annual meeting of the
American Society of Human Genetics.

Scientists already knew that every now and then RNA letters can be chemically modified or edited —
sort of the molecular equivalent of adding an umlaut to some letters. But those RNA editing events are
not common.

What Li and her colleagues discovered is quite common. RNA molecules contained misspellings at
20,000 different places in the genome, with about 10,000 different misspellings occurring in two or
more of the people studied. The most common of the 12 different types of misspellings was when an A
in the DNA was changed to G in the RNA. That change accounted for about a third of the misspellings.

Some researchers who saw Li’s presentation asked whether a virus used in growing the white blood
cells that the researchers studied might be the source of the shenanigans. Li and her collaborators had
wondered the same thing. In order to rule out the virus, the researchers analyzed skin cells from the
same people and found that RNA misspellings originally discovered in the white blood cells were also
in the skin cells. And the misspellings aren’t just rare, random mistakes. “When DNA and RNA differ
from each other it happens in nearly every RNA” copy, Li says.

The researchers don’t yet know how the RNA misspellings happen. They could be substitutions made
while the RNA copy is being made, or the changes could happen later. The consequences of the
misspellings are also unknown. For instance, misspellings might cause the RNA to be degraded faster
or interfere with the molecule’s ability to make proteins.
The Heat Was On: Atmospheric CO2 Triggered a Global Warming
Event 40 Million Years ago

Atmospheric CO2 was the primary driver of a 400,000-year global warming event, known as the

middle Eocene climatic optimum (MECO), according to a new study. The finding, which could
help climatologists better understand the precise relationship between CO2 concentration and
climate change today, is described in the November 5 issue of Science.

The climate trend across the entire Eocene, an epoch between 55 million and 34 million years
ago, was actually characterized by long and gradual cooling. Much of that activity took place
during the middle Eocene, when the planet transitioned from a warmer climate to a cooler one.
But the MECO (about 40 million years ago) interrupted that trend, representing the last major
temperature increase before the end of the epoch, which was marked by Antarctic glaciation. In
order to investigate the role of CO2during this warming episode, researchers analyzed sediment
taken from deep beneath the ocean floor off the eastern coast of Tasmania. The core contained a
record of fossils that spanned the relevant time interval.

Currently, climatologists have a much better understanding of the role short-term

feedbacks, such as changes in water vapor or sea ice. Incidentally, there were no glaciers
at the time of the MECO, so Hoeben's group could look exclusively at the relationship
between CO2 and temperature without having to account for the fact that changes in the
amount of sea ice can increase temperature, too. "We've shown that if you include those
long-term factors, then CO2 might very well be the leading factor for temperature
increase, especially in a world without a major ice sheet," Houben says.

The researchers relied on two separate organic proxies, also called paleothermometers,
to reconstruct changes in sea-surface temperature during the MECO. Both are based on
variation—due to temperature change—in structural characteristics of the molecular
remains of specific microorganisms. In other words, the team analyzed specific
molecules in which certain variations are known to be reflective of temperature change.
The study does leave one big question outstanding: Where did all the MECO CO 2come
from? This remains an area of speculation, Houben says, although scientists are fairly
sure the source was not organic. However the CO2 got there, the takeaway from this
study is simple: "In the past," Zachos says, "whenever atmospheric carbon dioxide levels
rise, the climate warms."
Genetic 'variation' linked to autism
ATLANTA, Nov. 5 (UPI) -- People with a genetic flaw in a particular chromosome have a higher risk
of autism and schizophrenia, U.S. researchers say.

While both conditions are known to be influenced by genetic factors, this is the first time a
specific flaw or variation leading to a very high risk has been identified, Britain's Daily Telegraph
reported.Researchers at Emory University analyzed the DNA of more than 23,000 patients with
autism, developmental delay, intellectual disability or schizophrenia and say they detected a
genetic deletion known as a copy number variation on a particular area -- chromosome 17 -- in 24
of those patients.Someone with this deletion may be almost 14 times more likely to develop
autism or schizophrenia than a person without it, David Ledbetter, one of the study's authors,
says.No such deletion was detected in any of the more than 52,000 healthy people acting as
controls, the researchers said."We have uncovered a copy number variation that confers a very
high risk for ASD, schizophrenia, and neurodevelopmental disorders," lead author Daniel Moreno-
De-Luca says.

Cancer vaccine moves a step closer

Published: Nov. 5, 2010 at 12:38 PM

CAMBRIDGE, England, Nov. 5 (UPI) -- A cancer-fighting vaccine that may help the body's immune
system attack tumors could be developed in the future, U.K. researchers say.Researchers at
Cambridge University have discovered the mechanism tumor cells use to protect themselves from
the body's immune system, and they say by turning off the mechanism the body might cure itself
of the disease, The Daily Telegraph reported Friday.The team found a protein known as fibroblast
activation protein alpha stops the body's immune system from attacking cancer cells.FAP is found
in stromal cells, a kind of cells in the immune system that normally rush to the scene of a wound
to aid healing.The cancer tricks the body into thinking it is an injury, and instead of destroying the
tumors it actually nurtures them.The researchers have discovered turning off FAP in the body
allows the immune system to naturally destroy the tumors.The process has been demonstrated in
mice but the researchers say that it should be transferable to humans. "The research is at an
early stage but it is not too far-fetched to suppose that what has been seen in mouse tumors will
also be found in human versions of the disease," said Douglas Fearon, the immunologist who led
the study."It is possible we have found a very big piece of the jigsaw," he said.

The findings could lead to a vaccine to turn off FAP that would not be administered as a
prevention in advance but only when cancer is identified in a patient, researchers say.
Substance in grapes may help treat malaria
ATLANTA, Nov. 7 (UPI) -- Resveratrol -- a substance found in the skin of dark grapes -- may help
treat malaria, U.S. researchers say.

Researchers at the National Institutes of Health say resveratrol, associated with anti-cancer and
heart health benefits, may also improve survival chances of those with severe malaria.

The study finds treating parasite-infected red blood cells with resveratrol significantly reduced
their ability to stick to the cells lining small blood vessels and reduces the probability of
developing severe clinical manifestations of malaria.

The study suggests resveratrol can be used with anti-malarial chemotherapy to improve the
survival chances of people with severe malaria.

"Our results demonstrate the possibility of a new therapy to treat severe malaria," Jordan A.
Zuspann of the National Institutes of Health, says in a statement. "We hope that we have
identified a way to ameliorate the severity of malaria in young African children."

The findings were presented at the annual meeting of the American Society of Tropical Medicine
and Hygiene held in Atlanta.

Laparoscopic surgery used on bowel tumors

LEEDS, England, Nov. 6 (UPI) -- British researchers say all bowel tumor patients should have the
option of laparoscopic surgery, despite past concerns the technique is ineffective.Lead author Dr.
David Jayne of the University of Leeds in England say results of a five-year study find this type of
surgery -- performed with only a small incision and shortens recovery time -- is safe and effective
long-term.The study, published in the British Journal of Surgery, confirms laparoscopic surgery
does not make patients with colorectal cancer more vulnerable to the disease returning. Some had
feared it would not be as good at removing all cancer cells from tissue around the tumor and that
after a few years, the cancer would simply come back -- especially in patients with rectal
cancer."There is still a body of surgeons who are skeptical about laparoscopic colorectal cancer
surgery and particularly laparoscopic rectal surgery," Jayne says in a statement. "These long-term
follow-up results should now help to convince any remaining skeptics that the minimally invasive
technique is safe and effective for most patients with colorectal cancer." Jayne and colleagues
conducted a multicenter study involving 27 hospitals with about 400 patients with colon cancer
and another 400 with rectal cancer. The study included tissue samples analysis to assess the
quality of surgery.
Liver hormone key to insulin resistance
KANAZAWA, Japan, Nov. 5 (UPI) -- A liver hormone has been identified as a cause of insulin
resistance, in which the body produces insulin but does not use it properly, researchers in Japan
say.

Researchers at Kanazawa University Graduate School of Medical Science in Japan suggest the liver
may offer a new avenue of treatment for insulin resistance and type 2 diabetes.

The studies in mice suggest a causal connection between a hormone produced by the liver and
insulin resistance. Normal mice given the hormone became insulin resistant and their blood sugar
levels rose. A treatment blocking the hormone's activity in the livers of diabetic and obese mice
improved their sensitivity to insulin and lowered blood sugar levels. However, the researchers
note the liver does not act alone in the development of insulin resistance. Fat tissue is a main
contributor to the development of insulin resistance by producing fat-derived hormones called
adipokines. The connection between the liver hormone and adipokine production, the researchers
say, will be the subject of further investigation.The findings are published in the journal Cell
Metabolism.

Test created for different prostate cancer

NEW YORK, Nov. 5 (UPI) -- U.S. researchers say there are different kinds of prostate cancer, some
more lethal than others, and they are working on tests to identify aggressive tumors.

Researchers at New York-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical

College in New York City have identified secondary mutations linked to more lethal prostate
cancers.

The study, published online in Genome Research, suggested the possibility of a test to identify
aggressive cancer tumors by their accumulated multiple mutations -- hybrid genes formed from
two previously separate genes -- known as fusions.

"In the future, these fusions, specific to certain types of prostate cancer, may help physicians
prescribe tailored therapies for their patients," study leader Dr. Mark Rubin says in a statement.
"This is an important step toward providing specific therapies that target individual cancer
variants, and our hope is these findings will help doctors diagnose a patient's specific disease."

Rubin and colleagues seek to co-develop a test for lethal prostate cancer with researchers at the
University of Michigan and two commercial partners, Gen-Probe and Ventana/Roche.