Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication Protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. binding proteins seem to stabilize single-stranded DNA and protect it from forming stem loops or being degraded by nucleases

GENE THERAPHY

Each gene has a special job to do. It carries blueprints(said to be instructions).
Each of our biological parents has two copies of each of their genes, and each parent passes along just one copy to make up the genes we have. Genes that are passed on to us determine many of our traits, such as our hair color and skin color and many other characteristics. Nowadays scientists are very busy studying genes.
Gene therapy uses the technology of genetic engineering to cure or treat a disease caused by a gene that has changed in some way. This is a new kind of medicine, and scientists are still doing experiments to see if it works. One method they are trying is replacing sick genes with healthy ones.Gene therapy is the insertion of genes into an individual's cells and tissues to treat diseases, such as hereditary diseases.Although the technology is still in its infancy, it has been used with some success. Scientific breakthroughs continue to move gene therapy toward mainstream medicine.The biology of human gene therapy remains complex and many techniques need further development.Gene therapy is nowadays the basis to many entertainment programs and popular video games.

PROPERTIES OF DNA

DNA is a long polymer made from repeating units called nucleotides.In living organisms, DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together.The backbone of the DNA strand is made from alternating phosphate and sugar residues.A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.
DNA can be twisted like a rope in a process called DNA supercoiling.DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms.
DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.
The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype.

GENETIC ENGINEERING

Genetic engineering ia a term that apply to the direct manipulation of an organism's genes. Genetic engineering uses the techniques of molecular cloning and transformation to alter the structure and characteristics.Genetic engineering techniques have been applied to various industries,medicine and agriculture.
Human genetic engineering is the modification of an individual's genotype with the aim of choosing the phenotype of a newborn or changing the existing phenotype of a child or adult.Genetic engineering is a laboratory technique used by scientists to change the DNA of living organisms. Genetic engineering is defined as a set of technologies that are used to change the genetic makeup of cells and move the genes from one species to another to produce new organisms. Genetic Enginering holds many promises for the future. It brings with it possibilities of longer, healthier lives.
With genetic engineering, we would have the ability to clone a loved one or a favorite pet, ending the pain of loss that comes from death. It would also give us the ability to grow replacement organs, limbs, skin, or virtually any other body part.

BIOLOGICAL FUNCTIONS

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.[64] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation which depends on the same interaction between RNA nucleotides. Alternatively, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here we focus on the interactions between DNA and other molecules that mediate the function of the genome.

DNA PROFILING

DNA profiling (also called DNA testing, DNA typing, or genetic fingerprinting) is a technique employed by forensic scientists to assist in the identification of individuals on the basis of their respective DNA profiles. DNA profiles are encrypted sets of numbers that reflect a person's DNA makeup, which can also be used as the person's identifier. The process begins with a sample of an individual's DNA Which is also called as Reference sample.
A reference sample is then analyzed to create the individual's DNA profile using one of a number of techniques, discussed below. The DNA profile is then compared against another sample to determine whether there is a genetic match.
The chemical structure of everyone's DNA is the same. The only difference between people (or any animal) is the order of the base pairs.DNA fingerprinting is a way of identifying a specific individual, rather than simply identifying a species or some particular trait. It is also known as genetic fingerprinting or DNA profiling.
The vast majority of a human's DNA will match exactly that of any other human, making distinguishing between two people rather difficult. DNA fingerprinting uses a specific type of DNA sequence, known as a microsatellite.

TRANSCRIPTION AND TRANSLATION

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA and TAG codons.

ALTERNATE DNA STRUCTURE

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.

The first published reports of A-DNA X-ray diffraction patterns— and also B-DNA used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, Watson and Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.

Although the `B-DNA form' is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription

QUADRUPLEX STRUCUTER OF DNA

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3' ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop

GENES AND GENOMES

Genomic DNA is located in the cell nucleus of eukaryotes, as well as small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequences such as promoters and enhancers, which control the transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma." However, DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.
T7 RNA polymerase (blue) producing a mRNA (green) from a DNA template (orange).

Some non-coding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes. An abundant form of non-coding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.

DNA BINDING PROTEINS

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.
The lambda repressor helix-turn-helix transcription factor bound to its DNA target

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter; this will change the accessibility of the DNA template to the polymerase.

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.

GENETIC ENGINEERING

Genetic engineering is a laboratory technique used by scientists to change the DNA of living organisms.

DNA is the blueprint for the individuality of an organism. The organism relies upon the information stored in its DNA for the management of every biochemical process. The life, growth and unique features of the organism depend on its DNA. The segments of DNA which have been associated with specific features or functions of an organism are called GENES

Molecular biologists have discovered many enzymes which change the structure of DNA in living organisms. Some of these enzymes can cut and join strands of DNA. Using such enzymes, scientists learned to cut specific genes from DNA and to build customized DNA using these genes. They also learned about vectors, strands of DNA such as viruses, which can infect a cell and insert themselves into its DNA.

With this knowledge, scientists started to build vectors which incorporated genes of their choosing and used the new vectors to insert these genes into the DNA of living organisms. Genetic engineers believe they can improve the foods we eat by doing this. For example, tomatoes are sensitive to frost. This shortens their growing season. Fish, on the other hand, survive in very cold water. Scientists identified a particular gene which enables a flounder to resist cold and used the technology of genetic engineering to insert this 'anti-freeze' gene into a tomato. This makes it possible to extend the growing season of the tomato.

FORENSIC

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is called genetic fingerprinting, or more accurately, DNA profiling. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.

People convicted of certain types of crimes may be required to provide a sample of DNA for a database. This has helped investigators solve old cases where only a DNA sample was obtained from the scene. DNA profiling can also be used to identify victims of mass casualty incidents. On the other hand, many convicted people have been released from prison on the basis of DNA techniques, which were not available when a crime had originally been committed.

BIOINFORMATICS

Bioinformatics the manipulation, searching, and data mining of DNA sequence data. The development of techniques to store and search DNA sequences have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory.[120] String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides. In other applications such as text editors, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near-worst-case behaviour due to their small number of distinct characters. The related problem of sequence alignment aims to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function. Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without annotations, which label the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products in an organism even before they have been isolated experimentally.

DNA NANOTECHNOLOGY

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.[124] DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based as well as using the "DNA origami" method) as well as three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.

HISTORY OF DNA RESEARCH

The discovery that DNA was the carrier of genetic information was a process that required many earlier discoveries. The existence of DNA was discovered in the mid 19th century. However, it was only in the early 20th century that researchers began suggesting that it might store genetic information.

Friedrich Miescher (1844-1895) discovered a substance he called "nuclein" in 1869. Somewhat later, he isolated a pure sample of the material now known as DNA from the sperm of salmon, and in 1889 his pupil, Richard Altmann, named it "nucleic acid". This substance was found to exist only in the chromosomes.

In 1929 Phoebus Levene at the Rockefeller Institute identified the components that make up a DNA Molecule. Those components are:

1. The four bases
   1. Adenine (A)
   2. Cytosine (C)
   3. Guanine (G)
   4. Thymine (T)
2. Sugar
3. Phosphate

He showed that the components of DNA were linked in the order phosphate-sugar-base. He called each of these units a nucleotide and suggested the DNA molecule consisted of a string of nucleotide units linked together through the phosphate groups, which are the 'backbone' of the molecule. However Levene thought the chain was short and that the bases repeated in the same fixed order. Torbjorn Caspersson and Einar Hammersten showed that DNA was a polymer.

This was only accepted after the structure of DNA was elucidated by James D. Watson and Francis Crick in their 1953 Nature publication. Watson and Crick proposed the central dogma of molecular biology in 1957, describing the process whereby proteins are produced from nucleic DNA. In 1962 Watson, Crick, and Maurice Wilkins jointly received the Nobel Prize for their determination of the structure of DNA. The Nobel Prize would not have been given to them if it hadn't been for Rosalind Franklin and her famous photograph, Photo Fifty-One. Franklin, however, did not get much attention until recently, because before the Nobel Prize was given to Watson, Crick, and Wilkins, Franklin died of ovarian cancer. The most probable reason Franklin contracted cancer was her exposure to radiation from X-ray diffraction which is what she had used to take the photograph, photo Fifty-one.

DNA profiling was developed in 1984 by English geneticist Alec Jeffreys of the University of Leicester, and was first used to convict Colin Pitchfork in 1988 in the Enderby murders case in Leicestershire, England. This has helped investigators solve old cases where the perpetrator was unknown and only a DNA sample was obtained from the scene (particularly in rape cases between strangers). This method is one of the most reliable techniques for identifying a criminal, but is not always perfect, for example if no DNA can be retrieved, or if the scene is contaminated with the DNA of several possible suspects.

DNA REPLICATION

Before a cell divides, its DNA is replicated (duplicated.) Because the two strands of a DNA molecule have complementary base pairs, the nucleotide sequence of each strand automatically supplies the information needed to produce its partner. If the two strands of a DNA molecule are separated, each can be used as a pattern or template to produce a complementary strand. Each template and its new complement together then form a new DNA double helix, identical to the original.

Before replication can occur, the length of the DNA double helix about to be copied must be unwound. In addition, the two strands must be separated, much like the two sides of a zipper, by breaking the weak hydrogen bonds that link the paired bases. Once the DNA strands have been unwound, they must be held apart to expose the bases so that new nucleotide partners can hydrogen-bond to them.

The enzyme DNA polymerase then moves along the exposed DNA strand, joining newly arrived nucleotides into a new DNA strand that is complementary to the template.

Each cell contains a family of more than thirty enzymes to insure the accurate replication of DNA.

Primers

Though DNA polymerase can elongate a polynucleotide strand by adding new nucleotides, it cannot start a strand from scratch because it can only bond new nucleotides to a free sugar (3') end of a nucleotide chain. DNA polymerase requires the assistance of a primer, a previously existing short strand of DNA (or RNA) that is complementary to the first part of the DNA segment being copied. This small strand of nucleotides anneals (binds) by complementary base pairing to the beginning of the area being copied. With the primer in place, DNA polymerase is then able to continue adding the rest of the pairs of the segment until a new double strand of DNA is completed. Primers are formed from free nucleotides in the cell by enzymes called DNA primases.

Replication occurs differently on antiparallel strands of DNA.

That nucleotides can be added only to the sugar or 3' end of the growing complementary chain presents no problem for the side of the DNA chain opening at its phosphate or 5' end. The primer that binds to the first few exposed bases will end with a sugar (3') where the phosphate of a new nucleotide can be attached. From there on, DNA polymerase can continuously synthesize the growing complementary strand. This strand of DNA is called the leading strand. A nice little animation of DNA synthesis on the leading strand can be seen at the Nobel Prize e-museum site at http://www.nobel.se/medicine/educational/dna/a/replication/replication_ani.html.

A different challenge faces DNA polymerase when the complementary side of the DNA molecule begins unzipping from its sugar (3') toward its phosphate (5') end. A primer of complementary molecules attaching to the opening end of this chain would have a phosphate not a sugar at its exposed end so that new nucleotides could not be joined. To get around this problem, this strand is synthesized in small pieces backward from the overall direction of replication. This strand is called the lagging strand. The short segments of newly assembled DNA from which the lagging strand is built are called Okazaki fragments. As replication proceeds and nucleotides are added to the 3' end of the Okazaki fragments, they come to meet each other. The primer fragments are then booted out by enzymes and replaced by appropriate DNA nucleotides. The whole thing is then stitched together by another enzyme called DNA ligase. The Nobel e-museum also has an animation of this process at http://www.nobel.se/medicine/educational/dna/a/replication/lagging_ani.html .

Replication occurs simultaeously at multiple places along a DNA strand.

Because human DNA is so very long (with up to 80 million base pairs in a chromosome) it unzips at multiple places along its length so that the replication process is going on simultaneously at hundreds of places along the length of the chain. Eventually these areas run together to form a complete chain. In humans, DNA is copied at about 50 base pairs per second. The process would take a month (rather than the hour it actually does) without these multiple places on the chromosome where replication can begin.

DNA replication is extraordinarily accurate.

DNA polymerase makes very few errors, and most of those that are made are quickly corrected by DNA polymerase and other enzymes that "proofread" the nucleotides added into the new DNA strand. If a newly added nucleotide is not complementary to the one on the template strand, these enzymes remove the nucleotide and replace it with the correct one. With this system, a cell's DNA is copied with less than one mistake in a billion nucleotides. This is equal to a person copying 100 large (1000 page) dictionaries word for word, and symbol for symbol, with only one error for the whole process!

STRUCTURE OF DNA MOLECULE

Although scientists as far back in history as Aristotle recognized that the features of one generation are passed on to the next (...like begets like...) it was not until the 1860's that the fundamental principles of genetic inheritance were described by Gregor Mendel. Mendel's work with common garden peas, pisum sativum, led him to hypothesize that phenotypic traits (physical characteristics) are the result of the interaction of discrete particles, which we now call genes, and that both parents provide particles which make up the characteristics of the offspring. His theories were, however, widely disregarded by scientists of the time. In the last quarter of the 19th century, however, microscopists and cytologists, interested in the process of cell division, developed both the equipment and the methods needed to visualize chromosomes and their division in the processes of mitosis (A. Schneider, 1873) and of meiosis (E. Beneden, 1883).

As the 20th century began many scientists noticed similarities in the theoretical behavior of Mendel's particles, and the visible behavior of the newly discovered chromosomes. It wasn't long before most scientists were convinced that the hereditary material responsible for giving living things their characteristic traits, and chromosomes must be one in the same. Yet, questions still remained. Chemical analysis of chromosomes showed them to be composed of both protein and DNA. Which substance carried the hereditary information? For many years most scientists favored the hypothesis that protein was the responsible molecule because of its comparative complexity when compared with DNA. After all, DNA is composed of a mere 4 subunits while protein is composed of 20, and DNA molecules are linear while proteins range from linear to multiply branched to globular. It appeared clear that the relatively simple structure of a DNA molecule could not carry all of the genetic information needed to account for the richly varied life in the world around us!

It was not until the late 1940's and early 1950's that most biologists accepted the evidence showing that DNA must be the chromosomal component that carries hereditary information. One of the most convincing experiments was that of Alfred Hershey and Martha Chase who, in 1952, used radioactive labeling to reach this conclusion(See Graphics). This team of biologists grew a particular type of phage, known as T2, in the presence of two different radioactive labels so that the phage DNA incorporated radioactive phosphorus (32P), while the protein incorporated radioactive sulfur (35S). They then allowed the labeled phage particles to infect non-radioactive bacteria and asked a very simple question: which label would they find associated with the infected cell? Their analysis showed that most of the 32P-label was found inside of the cell, while most of the 35S was found outside. This suggested to them that the proteins of the T2 phage remained outside of the newly infected bacterium while the phage-derived DNA was injected into the cell. They then showed that the phage derived DNA caused the infected cells to produce new phage particles. This elegant work showed, conclusively, that DNA is the molecule which holds genetic information. Meanwhile, much of the scientific world was asking questions about the physical structure of the DNA molecule, and the relationship of that structure to its complex functioning.