DNA Double Helix Molecule.

DNA Double Helix Molecule

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Only a very elementary outline can be presented here.

There is a remarkable similarity between the DNA molecule and a computer program.

The foundations of modern computer science were laid down by Janos von Neumann (1903–1957)

Unlike computer binary systems, the DNA molecule uses four basic units for storing information which are often shown in illustrations as the four aces of a deck of playing cards. Four types of data are essential to the working of the molecule.

The four bases or nucleotides are as follows:

A adenine Pairs with thymine in DNA or uracil in RNA

T thymine Pairs with adenine.

C cytosine recently found use in quantum computation. the classical bit —with additional dimensions associated to the quantum properties of a physical atom. The first time any quantum mechanical properties were harnessed to process information took place on August 1st in 1998 when researchers at Oxford implemented David Deutsch's algorithm on a two qubit NMRQC (Nuclear Magnetic Resonance Quantum Computer) based on the cytosine molecule. This molecule has found a place in Molecular Computing.

G guanine – in concentration from guano: sea-fowl excrement.Guanine is used as an additive to cosmetics and shampoo to give a pearly lustre.

The nucleotides bond together in four ways to make the rungs of the ladder: A+T, T+A, C+G and G+C, so that both sides of the ladder will have all four nucleotides. The backbones of the ladder consist of alternate sugar (deoxyribose) and phosphate molecules. The nucleotides bond to the sugar molecules. It is the sequence of the four types of ladder rungs that make up the program of the molecule in much the same way as ones and zeroes make up a computer program. The DNA molecule is in effect a Turing machine. The basic grouping of the base pairs is in groups of three called codons. The codon corresponds to a byte in computermemory. The three pair codon provides sixty four possible values. Some codons (UAA, UGA and UAG) act as delimiters and serve no other purpose. This corresponds to the NOP (no-operation) instruction of a computer program. When referring to a codon as UGA this implies the base pairs U+A, G+C and A+T but it is sufficient to mention only one side of the ladder.

A most astonishing feature of the molecule is that a trivial chemical reaction or heat can split the molecule right down the middle. The nucleotides are bonded by double or triple hydrogen bonds which can easily be broken. An enzyme called polymerase synthesises new chains of nucleotides. An enzyme called ligase links these fragments into a continuous strand and matches them to the original. The split DNA polymer is thus repaired into two identical molecules. This process can be performed in vitro (in glass) so that forensic scientists can increase the quantity of DNA when only an extremely small sample is available.

If any mistakes occur in the replication, this will result in a mutation. It should not be supposed that the molecule actually looks like a ladder. If the thread of the molecule could be seen in detail it would appear as a compact conglomeration of atoms. The molecule is of course too thin to be observed in detail by any microscopic means but it can be observed as a thread if heavily stained. The diameter is about two nanometres but the total unrolled length about two metres. In other words, an invisible but imaginable thread two meters long if stretched. Totaling more than 3Billion atoms string together in a orderly way. If you change one you can imagine the effect if all is known.

The genome occupies only about five centimetres of the molecule – no purpose for the rest of the molecule has been discovered. This is not to say that it is not very useful. This is the part that is used by forensic scientists for DNA fingerprinting. This is most useful for identifying criminals and settling paternity disputes. The DNA molecule would not survive very well as a long thread but is fortunately very compactly coiled up around spoollike proteins in chromosomes known as histones.

The spiral structure of DNA was discovered by Rosalind Franklin by means of X-Ray crystallography. The DNA ladder is twisted into a right hand spiral much the same as a right hand screw thread. The DNA polymers are directional; the one end has an exposed hydroxyl group on the deoxyribose and the other end an exposed phosphate group. This directionality is vitally important to the working of the molecule. It should be noted that DNA is not ‘alive’ but is only the specification for a Life form. Alive starts with an Electric pulse that continue the rest of your Life until your hart stop that beat or two.

Despite its extreme complexity, DNA has a remarkable ability for survival. DNA has actually been extracted from 30 000 year old ground sloth dung and it has even been suggested that DNA can be extracted from million year old samples! Studies of DNA taken from the extinct Mauritian Dodo have showed that it is related to the common pigeon. DNA has also been extracted from a quick-frozen ice age woolly mammoth. A most significant result of a DNA study was announced in 1997 which confirmed that the Neanderthals were a distinct species which had become extinct and did not contribute to the DNA of modern humans.

All plants and animals have chromosomes which form part of the cell nucleus of living tissue. The chromosomes in turn contains a vast number of genes along its length which define protein production. The name chromosome (coloured body) is a misnomer – an object of this size is much smaller than light wavelengths and cannot therefore have colour, but they can be microscopically observed if heavily stained. From the table given here, it will be seen that the number of chromosomes bears little relation to the size or complexity of the organism.

The cells of the human body each have twenty three pairs of chromosomes with matching shapes.One of these pairs will be the sex chromosomes which are designated XX in the case of females and XY for males. As the chromosomes come in pairs, the DNA molecules, and consequently genes, from each parent will also be paired. Males and females form sex cells which are contained in ova and sperm in the case of humans. The offspring develops when the chromosomes of the ova and sperm combine. Obviously the number of chromosomes cannot double with each new generation, so that the ova and sperm cells must each have only half the number of chromosomes. When sex cells are formed the process starts with two similar chromosomes which then exchange DNA material, split and then form four individual ovum or sperm cells. During reproduction the crossing over of genes results in offspring having DNA with genes from both parents.

The XX and XY arrangement ensures that there will be an equal chance of male or female offspring being produced. In humans, the males and females are physically quite different from head to toe, as well as mentally and emotionally, yet the only genetic difference is in one out of forty six chromosomes.

Individual variations of a gene are called alleles. The alleles are structurally similar but differ in nucleotide arrangement. The alleles can be either dominant or recessive. For example we can have AA, Aa, aA or aa alleles for a trait. The capital letter denotes dominant and the lower case recessive. If a flower is produced with ‘A’ representing blue petals and ‘a’ for white, and both parent chromosomes have Aa alleles, then three out of four flowers are likely to have blue petals. It is interesting to note that a recessive trait can be passed on to offspring without being apparent in the parents. The different alleles in humans determine inherited traits such as hair and eye colour, susceptibility to illness, bodily stature etc. Some traits such as height can also be influenced by environmental factors, such as the need for exercise, nutrition availability etc., other traits such as eye colour are not.

The DNA molecule is not directly involved in the expression of genes. The genes are transcribed into a second type of nucleic acid, RNA (Ribonucleic acid) which is typically single stranded and with the sugar ribose instead of deoxyribose. This molecule is much less stable than DNA. Not all parts of a gene are used for encoding products. Regions called introns are removed from the messenger RNA in a process called splicing and regions encoding products are called exons. A significant portion of gene coding is devoted to controlling and switching off protein production. This is somewhat similar to computer data transmission where a significant portion of the data stream exercises controlling, handshaking and data integrity functions. This is curiously referred to as ‘line protocol’. The control aspect of genes is obviously necessary – genes responsible for the growth of an ear should not produce fingers, toes or eyes like a Picasso painting.

Some viruses do not have DNA but store their entire genome as RNA. This allows their cellular hosts to directly synthesise their proteins without transcribing DNA. Viruses such as HIV are RNA retroviruses which require reverse transcription of their RNA genome into the DNA of their hosts before their proteins can be synthesised.

The self-repair aspect of DNA is astonishing to the point of miraculous. It has been estimated that the DNA in a single cell can be damaged up to 10 000 times a day by carcinogens and radiation. The DNA can even be damaged by products within the cell. The DNA molecule will take this damage in its stride but occasionally the damage will remain unattended resulting in the start of mutation or cancerous growth.

Shown here is DNA ligase repairing chromosomal damage. The three visable protein structures are:

The DNA binding domain (DBD) which is bound to the DNA minor groove both upstream and downstream of the damaged area.
The OB-fold domain (OBD) unwinds the DNA slightly over a span of six base pairs and is generally involved in nucleic acid binding.
The Adenylation domain (AdD) contains enzymatically active residues that join the broken nucleotides together by catalyzing the formation of a phosphodiester bond between a phosphate and hydroxyl group

Esters are chemical compounds derived by reacting an oxoacid (one containing an oxo group, X=O) with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH (hydroxyl) group is replaced by an -O-alkyl (alkoxy) group, and most commonly from carboxylic acids and alcohols. Basically, esters are formed by condensing an acid with an alcohol.Esters are ubiquitous. Many naturally occurring fats and oils are the fatty acid esters of glycerol. Esters with low molecular weight are commonly used as fragrances and found in essential oils and pheromones. Phosphoesters form the backbone of DNA molecules. Nitrate esters, such as nitroglycerin, are known for their explosive properties, while polyesters are important plastics, with monomers linked by ester moieties.

Development of the first synthetic cell by reconstructing the genome of a bacterium and producing a synthetic chromosome. The team started with the bacterium M. genitalium, an obligate intracellular parasite whose genome consists of 482 genes comprising 582,970 base pairs, arranged on one circular chromosome (the smallest genome of any known natural organism that can be grown in free culture). They then systematically removed genes to find a minimal set of 382 genes that can sustain life. This effort was also known as the Minimal Genome Project. Mycoplasma laboratorium is a planned partially synthetic species of bacterium derived from the genome of Mycoplasma genitalium

For each successive human generation the offspring will have a new DNA configuration. In addition to the DNA molecules that make up the chromosomes within the cell nuclei, the cells also have many organelles called mitochondria which contain circular DNA loops called mitochondrial DNA. The mitochondrial DNA does not express traits and does not change from one generation to the next unless mutations occur. Mitochondrial DNA is contained in ova but not in sperm so that this DNA can only be transmitted to the next generation by the female parent. Mitochondria therefore provide a useful means of tracing female ancestry back for as many generations as DNA can be found.

A remarkable project was launched in 2005 to study historical human migration patterns by analyzing DNA samples from hundreds of thousands of people from all parts of the world. This is a privately funded collaboration between IBM, the National Geographic Society and the Waitt Family Foundation. This huge anthropology project is expected to run for five years. The samples are taken by means of mouth swabs (buccal swabs). The project also includes the sale of selftesting kits which can be purchased through the post. People purchasing the kits can have the migration of their early ancestors determined either by mitochondrial DNA or chromosome-Y DNA. The mitochondrial DNA trace will give results for female ancestry and the chromosome Y test will show male ancestry. Women wishing to trace their male ancestry must obtain the swab from a close male family member. Profits from the sale of kits are ploughed into a Legacy Fund which will be spent on cultural preservation projects. This exciting project has already produced fascinating results but sadly it has also met with opposition from people who feel their tribal identity under threat.

The Human Genome Diversity Project (HGDP) was originally proposed by geneticist Luigi Cavalli-Sforza. A remarkable discovery was made when the mitochondrial DNA of Cheddar Man was compared with that of living local residents. The DNA was extracted from a molar of a 9 000 year old Briton who was found in Gough’s Cave in Cheddar Gorge, Somerset. The tests showed that many present day locals were descended from ancient Britons and not only from later invading foreigners as was widely believed.

The huge advances made in the sequencing and manipulation of DNA have resulted in the science of Genetic Engineering. The use of GM (genetically modified) crops is now widespread. We have here a similar situation to the discovery of nuclear fission. This was hoped to provide wonderful benefits including the availability of cheap and inexhaustible power. The manipulation of DNA has the potential of becoming a Pandora’s Box Constructing new life forms at bacterial level has already been Proved and shall continue. Intelegence and reason must make Triple sure and never loose control of the good and healthy. If we find we have lost control do not hesitate to use a Gama ray

The computer program aspect of the DNA molecule has not been lost on computer scientists. An enormous amount of research is being done on molecular computing using DNA molecules. This is the interface with our electronic computers so no one need have any fears that their bank balance will depend on a DNA molecule. In the original von Neumann / Turing design the computer instructions would always be performed in sequence, one at a time. The instructions could of course perform decision making and jump to various parts of the program as required and also perform repetitive loops. A way of increasing performance would be to have several processors working together in parallel but only specific applications can be speeded up in this way. By contrast, molecular computing would be massively parallel with thousands or even millions of processes being performed simultaneously.this mean a interface with real Life.The molecular computer holds out some hope that this can be performed in a more reasonable time.

Another remarkable possibility is the use of molecules for data storage. Information stored in DNA-like molecules would mean that millions of digitised photographs could be stored in a piece of material scarcely large enough to be visible. Finding a workable storage and retrieval method to access this data is a matter still in the realm of science fiction.This is where I am now. To find a way to unload al this images of Frozen moments in time.

The human genome contains 3.2 billion chemical nucleotide base pairs (A, C, T, and G).

· The average gene consists of 3,000 base pairs, but sizes vary greatly, with the largest known human gene being dystrophin at 2.4 million base pairs.

Functions are unknown for more than 50% of discovered genes.

The human genome sequence is almost exactly the same (99.9%) in all people.

· About 2% of the genome encodes instructions for the synthesis of proteins.

· Repeat sequences that do not code for proteins make up at least 50% of the human genome.

· Repeat sequences are thought to have no direct functions, but they shed light on chromosome structure and dynamics. Over time, these repeats reshape the genome by rearranging it, thereby creating entirely new genes or modifying and reshuffling existing genes.

· The human genome has a much greater portion (50%) of repeat sequences than the mustard weed (11 %), the worm (7%), and the fly (3%).

· Over 40°/o of predicted human proteins share similarity with fruit-fly or worm proteins.

· chromosome 1 (the largest human chromosome) has the most genes (3,168), and Y chromosome has the fewest (344).

· Particular gene sequences have been associated with numerous diseases and disorders, including breast cancer, muscle disease, deafness, and blindness.