Department Of Instrumentation

DNA Computing
Seminar
Kunal Ray

7th Semester.

09
DNA Computing – Seminar

Introduction: A DNA computer is basically a “nano-computer that uses DNA or

deoxyribonucleic acid to store information and perform calculations”. 1 Basically
speaking, DNA computers are the next generation microprocessors which use
DNA, chemistry and molecular biology instead of the regular or traditional silicon
based computer technologies. DNA computing or more generally, molecular
computing, is a fast developing inter-disciplinary area. Millions of natural
supercomputers exist inside living organisms, include homo-sapiens. The DNA
molecules, which make up our genes, have the potential to perform calculations
millions of times faster than the world’s fastest man-made computers. It has been
forecasted that DNA might one day be integrated into a computer chip to create a
so-called biochip that will have the capability of pushing computers even faster.
DNA molecules have already been harnessed to perform complex mathematical
calculations. While still in their infancy, DNA computers shall be able to store
billions of times more data than the conventional computers.

History: DNA computing as a field was first developed by Leonard Adleman of

the University of Southern California, in 1994.2 Adleman demonstrated a proof of
concept use of DNA as a form of computation which solved the seven point
Hamiltonian path problem. Since the initial Adleman experiments, advances have
been made and various Turing machines have been constructed. “Turing machines
are basic abstract symbol manipulating devices which, despite their simplicity, can
be adapted to simulate the logic of any computer algorithm. They were described
in 1936 by Alan Turing”.3

1
DNA Computer – Definition, http://www.webopedia.com/TERM/D/DNA_computer.html
th
Retrieved On July 5 , 2009.
2
Adleman, Leonard M., 1994, Molecular Computation Of Solutions To Combinational Problems, Science Journal.
3
Turing Machine – Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/wiki/Turing_machine
Retrieved On July 5th, 2009.
2
Kunal Ray, CUSAT
DNA Computing – Seminar

“In 2002, researchers at the Weizmann Institute of Science in Rehovot,

Israel, unveiled a programmable molecular computing machine composed of
enzymes and DNA molecules instead of silicon microchips”.4 On April 28th, 2004,
Ehud Shapiro, Yakov Benenson, Binyamin Gil, Uri Ben Dor and Rivka Adar at the
Weizmann Institute announced in the journal Nature that they had constructed a
DNA computer. “This was coupled with an input and output module and is capable
of diagnosing cancerous activity within a cell, and then releasing an anti-cancer
drug upon diagnosis”. 5 A schematic for the above can be shown as below:

Fig: Disease diagnosis and drug administration using DNA computers.

A more detailed explanation shall be provided as we progress with the topic. The
design was one of its kinds and hailed as “the smallest bio-molecular computer
ever”, according to the Guinness Book of World Records.

4
Computer made from DNA and enzymes,
http://news.nationalgeographic.com/news/2003/02/0224_030224_DNAcomputer.html
Retrieved On July 5th, 2009.
5
Adar, Rivka et al, 2004, An autonomous molecular computer for logical control of gene expression, Nature Journal.
3
Kunal Ray, CUSAT
DNA Computing – Seminar

Capability: The DNA computers shall come with a variety of definite advantages
over normal/conventional microprocessors using silicon chips. Some of them are
discussed below.

Parallel Computing: DNA computers by their inherent nature, work on the

principle of parallel computing. “Parallel computing is a principle according
to which, many calculations are carried out simultaneously”. 6 This means
that a DNA computer breaks down a given large problem into several
smaller modules and these are then solved concurrently. This essentially
means that initially complex problems which a conventional computer
would take years to solve can be solved within hours using DNA computers.
In order to understand the ability of parallel computing in DNA consider the
fact that a test tube filled with DNA can contain trillions of strands. Each
operation on the test tube of DNA is carried out on all strands of the tube in
parallel. Hence typically we have-

300,000,000,000,000
molecules at a time
Memory: A DNA computer a memory capacity much larger than any
conventional computer available at present. The picture below shows 1 gm
of DNA on a CD. The average CD has a storage space of 800 MB. But a
DNA computer can hold about 1× MB of data.

6
Almasi, G.S., Gottlieb, A., 1989, Highly Parallel Computing, Benjamin Cummings Publishers, Redwood City, CA.
4
Kunal Ray, CUSAT
DNA Computing – Seminar

Energy Consumption: The energy consumption for a DNA computer has

been reported to be very low when compared to conventional computers.

Structure of DNA: DNA (deoxyribonucleic acid) is the primary genetic material

in all living organisms - a molecule composed of two complementary strands that
are wound around each other in a double helix formation. The strands are
connected by base pairs that look like rungs in a ladder. Each base will pair with
only one other: adenine (A) pairs with thymine (T), guanine (G) pairs with
cytosine (C). The sequence of each single strand can therefore be deduced by the
identity of its partner. Genes are sections of DNA that code for a defined
biochemical function, usually the production of a protein. The DNA of an
organism may contain anywhere from a dozen genes, as in a virus, to tens of
thousands of genes in higher organisms like humans. The basic structure of a DNA
molecule can be illustrated below.

5
Kunal Ray, CUSAT
DNA Computing – Seminar

Fig: Structure of DNA (deoxyribonucleic acid)

The structure of a protein determines its function. The sequence of bases in a given
gene determines the structure of a protein. Thus the genetic code determines what
proteins an organism can make and what those proteins can do. It is estimated that
only 1-3% of the DNA in our cells codes for genes; the rest may be used as a
decoy to absorb mutations that could otherwise damage vital genes.

Technology – DNA Separation: Working with individual DNA molecules is

tricky. Current technologies involve chemically binding each DNA molecule to a
plastic bead, then trapping and moving the bead by hitting it with an intense beam
of photons from a laser. A team of researchers from Japan has found a way to drag

6
Kunal Ray, CUSAT
DNA Computing – Seminar

DNA molecules around without attaching them to a larger object. The researchers'
first approach was to sandwich the DNA between unconnected beads and move the
DNA indirectly by bombarding the beads with a laser. A schematic can be shown
below.

Fig: Laser Snatching Free Floating DNA. 7

Although that method worked, it required a high degree of skill to carry out. The
researchers went on to find an easier way: they made the beads much smaller and
used many more of them. Key to the method is the size of the beads. The

7
The DNA Packaging Motor – Seeking The Mechanism,
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A40182
Retrieved On July 6th, 2009.
7
Kunal Ray, CUSAT
DNA Computing – Seminar

researchers found that “a laser beam would trap, or aggregate a cluster of more
than 40 beads that were 200 nanometers in diameter, but would only trap a few
beads half that size. To demonstrate the technique, the researchers put the DNA in
a solution that contained 200-nanometer beads. When they focused a laser beam
into the solution, a group of beads aggregated at the point of focus. When they
focused the beam at the end of a single DNA molecule, a group of beads packed
tightly together around that point, and the researchers used the bead cluster to drag
the end of the molecule”. 8 The molecule can be released and re-trapped by
switching the laser off and on, and a single DNA molecule can be manipulated at
any point along its length. Combined with florescent labeling, which tags a
molecule so that it can be seen through an optical florescent microscope, the
method allows for real-time handling of DNA molecules.

Salient Properties of DNA Molecules: The DNA molecules have some salient
properties which differentiate it from other silicon based microprocessors and add
to their usefulness. Some of the properties of DNA molecules used for the purpose
of DNA computing are as follows. It is important that one understands the
procedures mentioned below to have a complete insight regarding the
manufacturing of a DNA computer.

Replication: Replication is one of the most important properties used in

DNA computing. Replication is the method by which any molecule can form
an exact replica of itself and the DNA gets embedded in both these daughter
molecules. “For a cell to divide, it must first replicate its DNA. The process
is initiated at specific points within the DNA molecule, known as origins”. 9

8
Laser Snatch Free Floating DNA, http://www.trnmag.com/Stories/2002/032002/Lasers_snatch_free-
floating_DNA_032002.html
Retrieved On July 6th, 2009.
9
Alberts B. et al, 2002, Molecular Biology Of The Cell, Garland Science, Chapter 5, DNA Replication Mechanisms.
8
Kunal Ray, CUSAT
DNA Computing – Seminar

These origins are targeted by proteins that separate the two strands and
initiate DNA synthesis. A schematic showing DNA replication can be given
below.

Fig: DNA Replication – Schematic10

DNA Extraction: In this method, it is possible to separate and bring

together different strands of DNA that are of the same type. Suppose that
we have a test tube containing DNA in which some of the molecules contain
the strand “s”. Then it is possible to separate all the strands in the test tube
that contain “s” as a subsequence and separate from those strands that do not
contain these subsequences. A schematic for the above operation is shown
below and the operation of separation and effectively extraction of DNA
molecules illustrated.

10
DNA Replication And Synthesis, http://library.thinkquest.org/C006188/basics/replication.htm
Retrieved On July 6th, 2009.
9
Kunal Ray, CUSAT
DNA Computing – Seminar

Fig: Separation & Extraction, DNA Strands. 11

DNA Annealing: This is the method by which two DNA strands can be
brought together and then paired together or melted to form one single
entity. A highly simplistic model can be shown below.

Fig: Two strands bearing s-subsequence coming closer.

11
DNA Separation, http://chemistry2.csudh.edu/rpendarvis/NuclAcids.html
Retrieved On July 6th, 2009.
10
Kunal Ray, CUSAT
DNA Computing – Seminar

Fig: Annealed Pair resulting in Single Entity.

The concept behind this is that “the hydrogen bonding between two
complementary sequences is weaker than the one that links nucleotides of
the same sequence. It is therefore possible to pair (anneal) or separate (melt)
to anti parallel and complementary single strands”.

Understanding DNA Computing – Hamiltonian Problem: There exists a

classical problem, known as the Hamiltonian problem or the “Travelling Salesman
Problem”, which can be used to explain the usefulness of DNA computing and its
definite edge over conventional silicon based microprocessors.

Problem Statement: Consider a salesman who has to travel to a number of cities

on a daily basis. Now the problem is to find for him the fastest route, without
taking him through the same city twice. A schematic for the problem can be shown
below. Now the problem seems to be simple enough if the number of cities is 5.
But what if the number of cities is 25 or for that matter 500 or even more. In such
cases, the conventional computer shall invariably take years to find out the
accurate answer. The reason for this is that it must generate a list of all the possible
paths and then search out the shortest path, an extremely time consuming task. But
using the DNA computing mechanism, the answer can be found accurately within
hours.

11
Kunal Ray, CUSAT
DNA Computing – Seminar

Delhi
(Source)

Mumbai
Kolkata

Bangalore
Kochi
(Destination)
Solution: The solution to the above problem can be found out using the
property of replication of DNA and by using the fact that we can use fluorescent
labeling to tag individual molecules in DNA. A single strand of DNA cannot yield
much power. But since DNAs can replicate themselves, so one can have as much
DNA as required to perform complex tasks like the one explained above. And
since DNA works on the principle of parallel processing, a number of options can
be checked simultaneously and the right answer can be arrived at instantly. So far,
this method has been successfully applied up to 15 cities. With advances taking
place almost daily, the number of cities shall shoot up, provided we have enough
DNA to go around with!! So let us see Adleman’s algorithm used to solve the
problem at hand.

o Generate all possible routes.

o Select itineraries that start with the proper city and end with the final city.

12
Kunal Ray, CUSAT
DNA Computing – Seminar

o Select itineraries with the correct number of cities.

o Select itineraries which contain each city only once.

Let us explain all the above steps one by one.

 Generating all possible routes: For this purpose, we encode all the cities
one by one as shown below.
Delhi GCTACG

Mumbai CTAGTA

Kolkata TCGTAC

Bangalore CTACGG

Kochi ATGCCG

The short single DNA is synthesized by a technology called DNA synthesizer. In

the next step, we encode all the itineraries by connecting the city sequences for
which routes exist. This can be shown below.

Bangalore

Bangalore Kochi Bangalore to

(CTACGG) Kochi
CGG ATG GCCTAG
Kochi

(ATGCCG)

GCCTAG

(After Hybridization)

13
Kunal Ray, CUSAT
DNA Computing – Seminar

 Select the desired itineraries: The next step is to select the itineraries that
start and end with the correct route. The strategy is to selectively cope and
amplify only that DNA which starts with Delhi and end with Kochi. This
can be shown below.

CGATGC TACGGC
(Start Primer) (End Primer)

Delhi Kochi
(source) (destination)

GCTACG ATGCCG

The technique used for the above operation is Polymerase Chain Reaction
(PCR). This technique allows the production of many copies of a specific
sequence of DNA.

 Select itineraries with correct no. of cities: Sort the DNA by length and
select the DNA whose length equals to 5 cities. The process can be shown
below. Generally, the DNA is a negatively charged molecule, having a
constant charge density. The GEL slows down the passing of DNA
depending on the lengths therefore, producing bands. “The technique used is
GEL Electrophoresis. It is used to differentiate between DNA molecules
having different lengths”.12

12
Gene Almanac, GEL Electrophoresis, http://www.dnalc.org/ddnalc/resources/electrophoresis.html
14
Kunal Ray, CUSAT
DNA Computing – Seminar

Fig: GEL Electrophoresis.

 Select the paths having complete set of cities: In this section, the DNA
molecules are successively filtered city by city, one city at a time. The
technique used for the above process is Affinity Purification. It is done by
attaching the compliment of the sequence in question to a substrate like
magnetic bead. The DNA which is contained in the sequence hybridizes
with the complement sequence on the beads. Graduated PCRs can be used if
we already have the city encodings. The procedure can be shown below.

Retrieved On July 7th, 2009.

15
Kunal Ray, CUSAT
DNA Computing – Seminar

CGATGC GATCAT AGCATG GATGCC TACGGC

GCTACG CTAGTA TCGTAC CTACGG ATGCCG

Delhi to Mumbai to Kolkata to Bangalore to

Mumbai Kolkata Bangalore Kochi

Hence, as shown above, through DNA computing, the shortest path from one city
to another can be calculated and the Hamiltonian problem be solved.

Biological Implementation of Computer Logic: The question which arises after

all this explanation is that how is it possible to implement the various computer
operations with the help of DNA strands. As an answer to this query, scientists
have successfully developed mechanisms, which can replicate the logical and
computational operations of a conventional computer. "The recent discovery of
DNA Logic Gates is the first step towards creating a DNA computer which has a
structure similar to an electronic PC”. 13 Given below is a comparison of the various
operations in a conventional computer and their biological implementation.

13
DNA Computing Technology, How Stuff Works?, http://computer.howstuffworks.com/dna-computer1.htm
Retrieved On July 7th, 2009.
16
Kunal Ray, CUSAT
DNA Computing – Seminar

Conventional Logic Biological Implementation

Sum: This adds a value x to all the Sum: In this a number is added to all the
numbers inside a set S. strands using the RST method.
Subtraction: This operation subtracts a Subtraction: In this, the same number is
value x from all numbers in a set S. removed from all the strands using RST.
Division: This step will separate the set Division: The necessary operation for
S into two different sets based on the this step of DNA computing is to
criteria C. If no criterion is given, then separate one tube of strands into two
components in these two sets are tubes. Each resultant tube will have
randomly picked from set S and S will approximately half of the strands of the
be evenly distributed into two sets S1 original tube. The criteria C can be
and S2. containing or not containing a certain
segment, e.g. ATTCG, and we may use
the metal bead method to extract them.
Union: The operation combines, in Union: This operation will simply pour
parallel, all the components of sets S1 two tubes of strands into one.
and S2 into set S.
Copy: This will produce a copy of S: Copy: We need to make copies of DNA
S1. strands of the original tube and double
the number of strands we have for this
copy operation. Best and easiest method
is PCR (explained above).
Select: This operation will select an Select: This procedure will actually
element of S following criteria C. If no extract out the strand we are looking for.
C is given, then an element is selected So, it will extract strands from tube S
randomly. following certain criteria C.

17
Kunal Ray, CUSAT
DNA Computing – Seminar

A schematic of the different logic cells can be given below as per their biological
implementation.

Fig: The Genetic NOT Gate.

Fig: The Genetic AND Gate.

As shown above, similar genetic analogy exists for other logic gates as well.
Finally, we can give a comparison of the conventional and DNA computers.

18
Kunal Ray, CUSAT
DNA Computing – Seminar

DNA Based Computers Classical Computers

Slow at individual operations. Fast at individual operations.
Can do billions of operations Can do substantially fewer operations
simultaneously. simultaneously.
Can provide huge memory in small Smaller memory. At most 10^14 bits.
space. One cubic centimeter of DNA
soup could store as much as 10^21bits
of information.
Setting up a problem may require Setting up only requires keyboard input.
considerable preparations.
DNA is sensitive to chemical Electronic data is vulnerable but can be
deterioration. backed up easily.

Conclusion: DNA, the genetic code of life itself has been the molecule of this
century and certainly for the next one. The future of DNA manipulation is speed,
automation and miniaturization. Perhaps it will not be good enough to play games
or surf the web, things traditional computers are good at, but it certainly might be
used in the study of logic, encryption, genetic programming and algorithms,
automata and lots of other things that haven’t even been invented yet!!

Therefore, it won’t be an exaggeration to state that DNA computing is

definitely the technology to watch out for in the coming years is certainly here to
stay.

19
Kunal Ray, CUSAT