Scientists Say They’ve Found a Code Beyond Genetics in DNA

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Researchers believe they have found a second code in DNA in addition to the genetic code.

The genetic code specifies all the proteins that a cell makes. The
second code, superimposed on the first, sets the placement of the
nucleosomes, miniature protein spools around which the DNA is looped.
The spools both protect and control access to the DNA itself.

The
discovery, if confirmed, could open new insights into the higher order
control of the genes, like the critical but still mysterious process by
which each type of human cell is allowed to activate the genes it needs
but cannot access the genes used by other types of cell.

The new
code is described in the current issue of Nature by Eran Segal of the
Weizmann Institute in Israel and Jonathan Widom of Northwestern University in Illinois and their colleagues.

There
are about 30 million nucleosomes in each human cell. So many are needed
because the DNA strand wraps around each one only 1.65 times, in a
twist containing 147 of its units, and the DNA molecule in a single
chromosome can be up to 225 million units in length.

Biologists
have suspected for years that some positions on the DNA, notably those
where it bends most easily, might be more favorable for nucleosomes
than others, but no overall pattern was apparent. Drs. Segal and Widom
analyzed the sequence at some 200 sites in the yeast genome where
nucleosomes are known to bind, and discovered that there is indeed a
hidden pattern.

Knowing the pattern, they were able to predict the placement of about 50 percent of the nucleosomes in other organisms.

The
pattern is a combination of sequences that makes it easier for the DNA
to bend itself and wrap tightly around a nucleosome. But the pattern
requires only some of the sequences to be present in each nucleosome
binding site, so it is not obvious. The looseness of its requirements
is presumably the reason it does not conflict with the genetic code,
which also has a little bit of redundancy or wiggle room built into it.

Having
the sequence of units in DNA determine the placement of nucleosomes
would explain a puzzling feature of transcription factors, the proteins
that activate genes. The transcription factors recognize short
sequences of DNA, about six to eight units in length, which lie just in
front of the gene to be transcribed.

But these short sequences
occur so often in the DNA that the transcription factors, it seemed,
must often bind to the wrong ones. Dr. Segal, a computational
biologist, believes that the wrong sites are in fact inaccessible
because they lie in the part of the DNA wrapped around a nucleosome.
The transcription factors can only see sites in the naked DNA that lies
between two nucleosomes.

The nucleosomes frequently move around,
letting the DNA float free when a gene has to be transcribed. Given
this constant flux, Dr. Segal said he was surprised they could predict
as many as half of the preferred nucleosome positions. But having
broken the code, “We think that for the first time we have a real
quantitative handle” on exploring how the nucleosomes and other
proteins interact to control the DNA, he said.

The other 50
percent of the positions may be determined by competition between the
nucleosomes and other proteins, Dr. Segal suggested.

Several
experts said the new result was plausible because it generalized the
longstanding idea that DNA is more bendable at certain sequences, which
should therefore favor nucleosome positioning.

“I think it’s really interesting,” said Bradley Bernstein, a biologist at Massachusetts General Hospital.

Jerry Workman of the Stowers Institute in Kansas City said the
detection of the nucleosome code was “a profound insight if true,”
because it would explain many aspects of how the DNA is controlled.

The
nucleosome is made up of proteins known as histones, which are among
the most highly conserved in evolution, meaning that they change very
little from one species to another. A histone of peas and cows differs
in just 2 of its 102 amino acid units. The conservation is usually
attributed to the precise fit required between the histones and the DNA
wound around them. But another reason, Dr. Segal suggested, could be
that any change would interfere with the nucleosomes’ ability to find
their assigned positions on the DNA.

In the genetic code, sets of
three DNA units specify various kinds of amino acid, the units of
proteins. A curious feature of the code is that it is redundant,
meaning that a given amino acid can be defined by any of several
different triplets. Biologists have long speculated that the redundancy
may have been designed so as to coexist with some other kind of code,
and this, Dr. Segal said, could be the nucleosome code.

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Computer Made from DNA and Enzymes

from: http://news.nationalgeographic.com/news/2003/02/0224_030224_DNAcomputer.html

Stefan Lovgren
for National Geographic News

February 24, 2003

Israeli scientists have devised a computer that can perform 330
trillion operations per second, more than 100,000 times the speed of
the fastest PC. The secret: It runs on DNA.

A year ago, researchers from the Weizmann Institute of Science
in Rehovot, Israel, unveiled a programmable molecular computing machine
composed of enzymes and DNA molecules instead of silicon microchips.
Now the team has gone one step further. In the new device, the single
DNA molecule that provides the computer with the input data also
provides all the necessary fuel.

The design is considered a giant step in DNA computing. The Guinness
World Records last week recognized the computer as "the smallest
biological computing device" ever constructed. DNA computing is in its
infancy, and its implications are only beginning to be explored. But it
could transform the future of computers, especially in pharmaceutical
and biomedical applications.

Following Mother Nature's Lead

Biochemical "nanocomputers" already exist in nature; they are
manifest in all living things. But they're largely uncontrollable by
humans. We cannot, for example, program a tree to calculate the digits
of pi. The idea of using DNA to store and process information took off
in 1994 when a California scientist first used DNA in a test tube to
solve a simple mathematical problem.

Since then, several research groups have proposed designs for DNA
computers, but those attempts have relied on an energetic molecule
called ATP for fuel. "This re-designed device uses its DNA input as its
source of fuel," said Ehud Shapiro, who led the Israeli research team.

Think of DNA as software, and enzymes as hardware. Put them together in
a test tube. The way in which these molecules undergo chemical
reactions with each other allows simple operations to be performed as a
byproduct of the reactions. The scientists tell the devices what to do
by controlling the composition of the DNA software molecules. It's a
completely different approach to pushing electrons around a dry circuit
in a conventional computer.

To the naked eye, the DNA computer looks like clear water
solution in a test tube. There is no mechanical device. A trillion
bio-molecular devices could fit into a single drop of water. Instead of
showing up on a computer screen, results are analyzed using a technique
that allows scientists to see the length of the DNA output molecule.

"Once the input, software, and hardware molecules are mixed in
a solution it operates to completion without intervention," said David
Hawksett, the science judge at Guinness World Records. "If you want to
present the output to the naked eye, human manipulation is needed."

Don't Run to the PC Store Just Yet

As of now, the DNA computer can only perform rudimentary
functions, and it has no practical applications. "Our computer is
programmable, but it's not universal," said Shapiro. "There are
computing tasks it inherently can't do."

The device can check whether a list of zeros and ones has an even
number of ones. The computer cannot count how many ones are in a list,
since it has a finite memory and the number of ones might exceed its
memory size. Also, it can only answer yes or no to a question. It
can't, for example, correct a misspelled word.

In terms of speed and size, however, DNA computers
surpass conventional computers. While scientists say silicon chips
cannot be scaled down much further, the DNA molecule found in the
nucleus of all cells can hold more information in a cubic centimeter
than a trillion music CDs. A spoonful of Shapiro's "computer soup"
contains 15,000 trillion computers. And its energy-efficiency is more
than a million times that of a PC.
While a desktop PC is designed to perform one calculation very fast,
DNA strands produce billions of potential answers simultaneously. This
makes the DNA computer suitable for solving "fuzzy logic" problems that
have many possible solutions rather than the either/or logic of binary
computers. In the future, some speculate, there may be hybrid machines
that use traditional silicon for normal processing tasks but have DNA
co-processors that can take over specific tasks they would be more
suitable for.

Doctors in a Cell

Perhaps most importantly, DNA computing devices could revolutionize the
pharmaceutical and biomedical fields. Some scientists predict a future
where our bodies are patrolled by tiny DNA computers that monitor our
well-being and release the right drugs to repair damaged or unhealthy
tissue.

"Autonomous bio-molecular computers may be able to work as 'doctors in
a cell,' operating inside living cells and sensing anomalies in the
host," said Shapiro. "Consulting their programmed medical knowledge,
the computers could respond to anomalies by synthesizing and releasing
drugs."

DNA computing research is going so fast that its potential is
still emerging. "This is an area of research that leaves the science
fiction writers struggling to keep up," said Hawksett from the Guinness
World Records.

A summary of the research conducted by scientists at the
Weitzmann Institute of Science is published in today's online edition
of the Proceedings of the National Academy of Sciences.

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DNA Molecules Display Telepathy-like Quality

http://www.livescience.com/health/080124-dna-telepathy.html

DNA molecules can display what almost seems like telepathy, research now reveals.

Double helixes of DNA can recognize matching molecules from a distance
and then gather together, all seemingly without help from any othermolecules,
scientists find. Previously, under the classic understandingof DNA, scientists had
no reason to suspect that double helixes of the
molecule could sort themselves by type, let alone seek each other out. The spiraling structure of DNA includes strings of molecules called bases.

Each of its four bases,commonly known by the letters A, T, C and G, is chemically
attracted toa specific partner — A likes binding to T, and C to G. The scheme binds
paired strands of DNA into the double helix the molecule is famous for.

Scientists investigated double-stranded DNA tagged with fluorescent
compounds. These molecules were placed in saltwater that contained no
proteins or other material that could interfere with the experiment or
help the DNA molecules communicate.

Curiously, DNA with identical sequences of bases were roughly twice
as likely to gather together as DNA molecules with different sequences.

The known interactions that draw the bases together are not the factor
bringing these double helixes close. Double helixes of DNA keep their
bases on their insides. On their outsides, they have highly
electrically charged chains of sugars and phosphates, which obscure the
forces that pull bases together. Although it looks as if spooky action or telepathic recognition is
going on, DNA operates under the laws of physics, not the supernatural.

To understand what researchers conjecture is really happening, think of
double helixes of DNA as corkscrews. The bases that make up a strand of
DNA each cause the corkscrew to bend one way or the other.
Double-stranded DNA with identical sequences each result in corkscrews
"whose ridges and grooves match up," said researcher Sergey Leikin, a
physical biochemist at the National Institute of Child Health and Human
Development in Bethesda, Md.

The electrically charged chains of sugars and phosphates of double
helixes of DNA cause the molecules to repel each other. However,
identical DNA double helixes have matching curves, meaning they repel
each other the least, Leikin explained. The scientists conjecture such
"telepathy" might help DNA molecules line up properly before they get
shuffled around. This could help avoiderrors in how DNA combines,
errors that underpin cancer, aging and other health problems.

Also, the proper shuffling of DNA is essential to sexual reproduction,
as it helps ensure genetic diversity among offspring, Leikin added.

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First artificial DNA a step towards biological computers

from: http://arstechnica.com/news.ars/post/20080708-first-artificial-dna-a-step-towards-biological-computers.html

It has been over 50 years since the discovery of the double-stranded
nature of DNA, and over that half-century and more we have learned a
lot about deoxyribonucleic acid, from the fact that it organizes into a
double-stranded double helix all the way to having sequenced the entire
DNA of humans and a range of other organisms. Now, according to a paper
published in the Journal of the American Chemical Society, a team in Japan has created the world's first DNA strand made from artificial bases.

As information storage systems go, DNA is not bad. Just four different
bases (adenine, thymine, guanine, and cytosine) are all that's needed
to code for 20 different amino acids, using three base codons (e.g.
AUG). In fact, the four-base, triplet codon system has the potential to
be able to store information for more than just 20 amino acids; there
are 64 potential combinations, so several amino acids have multiple
codons, along with three stop codons that tell the cellular machinery
involved that the sequence is done.

Along the way, people have looked at DNA and thought that it ought
to be possible to use DNA to store nonbiological data. Better still, it
can pack that information into far smaller packages than is possible
with solid state memory or even the densest hard drive platters. There
have also been experiments that use DNA sequences to perform parallel
processing, as we covered last year.

But we needn't be limited to the four complementary bases, and that's
just what has been shown by a Japanese team, who have published details
of their creation of an artificial DNA strand. All the components of
their DNA product are nonnatural, yet they spontaneously form
right-handed duplexes with the corresponding opposite base, and these
bonds have very similar properties to those of natural DNA.

The hope is that this artificial DNA could have a range of
applications in the real world, from the aforementioned DNA computing
proposals, along with using DNA to store data, to using it in nanotech
settings. Artificial DNA has similar physical properties to
common-or-garden DNA without being degraded by enzymes such as DNase
(which is found everywhere), a factor that would make it quite useful
for any kind of biomedical setting.

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