Life Science Essay

[Harley Scarow]

DNA (Deoxyribonucleic Acid)

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Deoxyribonucleic acid (DNA) is a nucleic acid —usually in the form of a double helix— that contains the genetic instructions specifying the biological development of all cellular forms of life, and most viruses. DNA is a long polymer of nucleotides and encodes the sequence of the amino acid residues in proteins using the genetic code, a triplet code of nucleotides. In complex eukaryotic cells such as those from plants, animals, fungi and protists, most of the DNA is located in the cell nucleus. By contrast, in simpler cells called prokaryotes, including the eubacteria and archaea, DNA is not separated from the cytoplasm by a nuclear envelope. The cellular organelles known as chloroplasts and mitochondria also carry DNA. DNA is often referred to as the molecule of heredity as it is responsible for the genetic propagation of most inherited traits. In humans, these traits can range from hair colour to disease susceptibility. During cell division, DNA is replicated and can be transmitted to offspring during reproduction. Lineage studies can be done based on the facts that the mitochondrial DNA only comes from the mother, and the male Y chromosome only comes from the father. Every person's DNA, their genome, is inherited from both parents. The mother's mitochondrial DNA together with twenty-three chromosomes from each parent combine to form the genome of a zygote, the fertilized egg. As a result, with certain exceptions such as red blood cells, most human cells contain 23 pairs of chromosomes, together with mitochondrial DNA inherited from the mother.

A strand of DNA contains genes, areas that regulate genes, and areas that either have no function, or a function which we don’t know; DNA is organized as two complementary strands, head-to-toe, with hydrogen bonds between them that can be unzipped like a zipper, separating the strands — contrary to a common misconception, DNA isn’t a single molecule, but rather a pair of molecules joined by these bonds; DNA is a chain of chemical "building blocks", called "bases", of which there are four types: these can be abbreviated A, T, C, and G. Each base can only "pair up" with one single predetermined other base: A+T, T+A, C+G and G+C are the only possible combinations; that is, an "A" on one strand of double-stranded DNA will "mate" properly only with a "T" on the other, complementary strand; U replaces T, notably in PBS1 phage DNA; U replaces T in RNA. The base components of nucleic acids can be polymerized in any order giving the molecules uniqueness; DNA is an acid because of phosphate groups between each deoxyribose. This is the main reason why DNA has a negative charge. The "polarity" of each pair is important: A+T is not the same as T+A, just as C+G is not the same as G+C; For each given base, there’s one possible complementary base, so naming the bases on the conventionally chosen side of the strand is enough to describe the double-strand sequence; The genetic information contained in a strand of DNA is determined by the sequence of bases along its length; The cell begins DNA replication by forcibly unzipping the DNA double strand down the middle, and then recreates the other half of each new single strand by exposing each half to a mixture of the four bases. An enzyme makes a new strand by finding the correct base in the mixture and pairing it with the original strand. In this way, the base on the old strand dictates which base will be on the new strand, and the cell ends up with an extra copy of its DNA. Mutations are simply chemical imperfections in this process: a base is accidentally skipped, inserted, or incorrectly copied, or the chain is trimmed, or added to; many basic mutations can be described as combinations of these accidental "operations". Mutations can also occur through chemical damage, light, or through other more complicated gene swapping events. DNA molecules that act as enzymes are known in laboratories, but none have been known to be found in life so far. In addition to the traditionally viewed duplex form of DNA, DNA can also acquire triplex and quadraplex forms. Here instead of the Watson Crick base pairing, Hoogsten base pairing comes into picture. DNA differs from ribonucleic acid by having a sugar 2-deoxyribose instead of ribose in its backbone. This is the basic chemical distinction of RNA and DNA.

Forensic scientists can use DNA located in blood, semen, skin, saliva or hair left at the scene of a crime to identify a possible suspect, a process called genetic fingerprinting or DNA profiling. In DNA profiling the relative lengths of sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared. DNA profiling was developed in 1984 by English geneticist Alec Jeffreys, and was first used to convict Colin Pitchfork in 1988 in the Enderby murders case in Leicestershire, England. Many jurisdictions require convicts of certain types of crimes to provide a sample of DNA for inclusion in a computerized database. This has helped investigators solve old cases where the perpetrator was unknown and only a DNA sample was obtained from the scene. 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. An extremely important note: Despite its biological origins, DNA plays an important role in computer science, both as a motivating research problem and as a method of computation in itself, called DNA computing, not only for biological origins.As a simple example, research on string searching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, was motivated by DNA research, where it is used to find specific sequences of nucleotides in a large sequence. In other applications like text editors, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near-worst-case behavior due to their small number of distinct characters. Databases have also been strongly motivated by DNA research, which requires special tools for storing and manipulating DNA sequences. Databases specialized for this purpose are called genomic databases, and have a number of unique technical challenges associated with the operations of approximate matching, sequence comparison, finding repeating patterns, and homology searching. In 1994, Leonard Adleman of the University of Southern California made headlines when he discovered a way of solving the directed Hamiltonian path problem, an NP-complete problem, using tools from molecular biology, in particular DNA. The new approach, dubbed DNA computing, has practical advantages over traditional computers in power use, space use, and efficiency, due to its ability to highly parallelize the computation, although there is labor worth mentioning involved in retrieving the answers. A number of other problems, including simulation of various abstract machines, the boolean satisfiability problem, and the bounded version of the Post correspondence problem, have since been analyzed using DNA computing. Due to its compactness, DNA also has a theoretical role in cryptography, where in particular it allows unbreakable one-time pads to be efficiently constructed and used. DNA research is also used to follow the course of human populations over time. DNA evidence is also being used to try to identify the Ten Lost Tribes of Israel DNA has also been used to look at fairly recent issues of family relationships, such as establishing some manner of familial relationship between the descendents of Sally Hemings and the family of Thomas Jefferson.

Sometimes called the molecule of heredity, DNA macromolecules as some think of them aren’t single molecules; They are pairs of molecules, which entwine like vines to form a double helix. Each vine-like molecule is a strand of DNA: a chemically linked chain of nucleotides, each of which consists of a sugar, a phosphate and one of five kinds of nucleobases. Because DNA strands are composed of these nucleotide subunits, they are polymers. The diversity of the bases means that there are five kinds of nucleotides, which are commonly referred to by the identity of their bases. These are adenine (A), thymine (T), uracil (U), cytosine (C), and guanine (G). U is rarely found in DNA except as a result of chemical degradation of C, but in some viruses, notably PBS1 phage DNA, U completely replaces the usual T in its DNA. Similarly, RNA usually contains U in place of T, but in certain RNAs such as transfer RNA, T is always found in some positions. Thus, the only true difference between DNA and RNA is the sugar, 2-deoxyribose in DNA and ribose in RNA. In a DNA double helix, two polynucleotide strands can associate through the hydrophobic effect and pi stacking. Specificity of which strands stay associated is determined by complementary pairing. Each base forms hydrogen bonds readily to only one other -- A to T and C to G -- so that the identity of the base on one strand dictates the strength of the association; the more complementary bases exist, the stronger and longer-lasting the association. The cell's machinery is capable of melting or disassociating a DNA double helix, and using each DNA strand as a template for synthesizing a new strand which is nearly identical to the previous strand. Errors that occur in the synthesis are known as mutations. The process known as PCR (polymerase chain reaction) mimics this process in vitro in a nonliving system. Because pairing causes the nucleotide bases to face the helical axis, the sugar and phosphate groups of the nucleotides run along the outside; the two chains they form are sometimes called the backbones of the helix. In fact, it is chemical bonds between the phosphates and the sugars that link one nucleotide to the next in the DNA strand.

Within a gene, the sequence of nucleotides along a DNA strand defines a messenger RNA sequence which then defines a protein, that an organism is liable to manufacture or express at one or several points in its life using the information of the sequence. The relationship between the nucleotide sequence and the amino-acid sequence of the protein is determined by simple cellular rules of translation, known collectively as the genetic code. The genetic code is made up of three-letter 'words' (termed a codon) formed from a sequence of three nucleotides. These codons can then be translated with messenger RNA and then transfer RNA, with a codon corresponding to a particular amino acid. There are 64 possible codons that encode 20 amino acids. Most amino acids, therefore, have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region, namely the UAA, UGA and UAG codons. In many species, only a small fraction of the total sequence of the genome appears to encode protein. For example, only about 1.5% of the human genome consists of protein-coding exons. The function of the rest is a matter of speculation. It is known that certain nucleotide sequences specify affinity for DNA binding proteins, which play a wide variety of vital roles, in particular through control of replication and transcription. These sequences are frequently called regulatory sequences, and researchers assume that so far they have identified only a tiny fraction of the total that exist. Junk DNA represents sequences that do not yet appear to contain genes or to have a function. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size among species represent a long-standing puzzle in DNA research known as the C-value enigma. Some DNA sequences play structural roles in chromosomes. Telomers and centromeres typically contain few protein-coding genes, but are important for the function and stability of chromosomes. Some genes code for RNA genes. Some RNA genes code for transcripts that function as regulatory RNAs that influence the function of other RNA molecules. The intron-exon structure of some genes is important for allowing alternative splicing of pre-mRNA which allows several different proteins to be made from the same gene. Some non-coding DNA represents pseudogenes that can be used as raw material for the creation of new genes with new functions. Some non-coding DNA provided hot-spots for duplication of short DNA regions; such sequence duplication has been the major form of genetic change in the human lineage. Exons interspersed with introns allows for exon shuffling and the creation of modified genes that might have new adaptive functions. Large amounts of non-coding DNA is probably adaptive in that it provides chromosomal regions where recombination between homologous portions of chromosomes can take place without disrupting the function of genes. Some biologists such as Stuart Kauffman have speculated that non-coding DNA may modify the rate of evolution of a species. Sequence also determines a DNA segment's susceptibility to cleavage by restriction enzymes, the quintessential tools of genetic engineering. The position of cleavage sites throughout an individual's genome determines one kind of an individual's DNA fingerprint.

DNA replication or DNA synthesis is the process of copying the double-stranded DNA prior to cell division. The two resulting double strands are generally almost perfectly identical, but occasionally errors in replication or exposure to chemicals, or radiation can result in a less than perfect copy, and each of them consists of one original and one newly synthesized strand. This is called semiconservative replication. The process of replication consists of three steps: initiation, elongation and termination.

The hydrogen bonds between the strands of the double helix are weak enough that they can be easily separated by enzymes. Enzymes known as helicases unwind the strands to facilitate the advance of sequence-reading enzymes such as DNA polymerase. The unwinding requires that helicases chemically cleave the phosphate backbone of one of the strands so that it can swivel around the other. The strands can also be separated by gentle heating, as used in PCR, provided they have fewer than about 10,000 base pairs. The intertwining of the DNA strands makes long segments difficult to separate. When the ends of a piece of double-helical DNA are joined so that it forms a circle, as in plasmid DNA, the strands are topologically knotted. This means they cannot be separated by gentle heating or by any process that does not involve breaking a strand. The task of unknotting topologically linked strands of DNA falls to enzymes known as topoisomerases. Some of these enzymes unknot circular DNA by cleaving two strands so that another double-stranded segment can pass through. Unknotting is required for the replication of circular DNA as well as for various types of recombination in linear DNA. The narrow breadth of the double helix makes it impossible to detect by conventional electron microscopy, except by heavy staining. At the same time, the DNA found in many cells can be macroscopic in length -- approximately 2 meters long for strands in a human chromosome [4]. Consequently, cells must compact or package DNA to carry it within them. This is one of the functions of the chromosomes, which contain spool-like proteins known as histones, around which DNA winds. When DNA is in solution, it undergoes conformational fluctuations due to the energy available in the thermal bath. For entropic reasons, more floppy states are thermally accessible than stretched out states; for this reason, a single molecule of DNA stretches similarly to a rubber band. Using optical tweezers, the entropic stretching behavior of DNA has been studied and analyzed from a polymer physics perspective, and it has been found that DNA behaves like the Kratky-Porod worm-like chain model with a persistence length of about 53 nm. Furthermore, DNA undergoes a stretching phase transition at a force of 65 pN; above this force, DNA is thought to take the form that Linus Pauling originally hypothesized, with the phosphates in the middle and bases splayed outward. This proposed structure for overstretched DNA has been called P-form DNA, in honor of Pauling. The DNA helix can assume one of three slightly different geometries, of which the B form described by James D. Watson and Francis Crick is believed to predominate in cells. It is 2 nanometres wide and extends 3.4 nanometres per 10 bp of sequence. This is also the approximate length of sequence in which the double helix makes one complete turn about its axis. This frequency of twist depends largely on stacking forces that each base exerts on its neighbors in the chain. The B form of the DNA helix twists 360° per 10 bp in the absence of strain. But many molecular biological processes can induce strain. A DNA segment with excess or insufficient helical twisting is referred to, respectively, as positively or negatively "supercoiled". DNA in vivo is typically negatively supercoiled, which facilitates the unwinding of the double-helix required for RNA transcription. There are four conformations that the ribofuranose rings in nucleotides can acquire: C-2' endo, C-2' exo, C-3' endo, and C-3' exo. Ribose is usually in C-3'endo, while deoxyribose is usually in the C-2' endo sugar pucker conformation. The A and B forms differ mainly in their sugar pucker. In the A form, the C3' configuration is above the sugar ring, whilst the C2' configuration is below it. Thus, the A form is described as C3'-endo. Likewise, in the B form, the C2' configuration is above the sugar ring, whilst C3' is below; this is called C2'-endo. Altered sugar puckering in A-DNA results in shortening the distance between adjacent phosphates by around one angstrom. This gives 11 to 12 base pairs to each helix in the DNA strand, instead of 10.5 in B-DNA. Sugar pucker gives uniform ribbon shape to DNA, a cylindrical open core, and also a deep major groove more narrow and pronounced that grooves found in B-DNA. The two other known double-helical forms of DNA, called A and Z, differ modestly in their geometry and dimensions. The A form appears likely to occur only in dehydrated samples of DNA, such as those used in crystallographic experiments, and possibly in hybrid pairings of DNA and RNA strands. Segments of DNA that cells have methylated for regulatory purposes may adopt the Z geometry, in which the strands turn about the helical axis like a mirror image of the B form. Other, including non-helical, forms of DNA have been described, for example a side-by-side configuration. Indeed, it is far from certain that the B-form double helix is the dominant form in living cells.

The asymmetric shape and linkage of nucleotides means that a DNA strand always has a discernible orientation or directionality. Because of this directionality, close inspection of a double helix reveals that nucleotides are heading one way along one strand, and the other way along the other strand. This arrangement of the strands is called antiparallel. For reasons of chemical nomenclature, people who work with DNA refer to the asymmetric ends of. Within a cell, the enzymes that perform replication and transcription read DNA in the 3 to 5 direction", while the enzymes that perform translation read in the opposite direction. However, because chemically produced DNA is synthesized and manipulated in the opposite or in non-directional manners, the orientation should not be assumed. In a vertically oriented double helix, the 3' strand is said to be ascending while the 5' strand is said to be descending. As a result of their antiparallel arrangement and the sequence-reading preferences of enzymes, even if both strands carried identical instead of complementary sequences, cells could properly translate only one of them. The other strand a cell can only read backwards. Molecular biologists call a sequence sense if it is translated or translatable, and they call its complement antisense. It follows then, somewhat paradoxically, that the template for transcription is the antisense strand. The resulting transcript is an RNA replica of the sense strand and is itself sense. A small proportion of genes in prokaryotes, and more in plasmids and viruses, blur the distinction made above between sense and antisense strands. Certain sequences of their genomes do double duty, encoding one protein when read 5' to 3' along one strand, and a second protein when read in the opposite direction along the other strand. As a result, the genomes of these viruses are unusually compact for the number of genes they contain, which biologists view as an adaptation. This merely confirms that there is no biological distinction between the two strands of the double helix. Indeed, typically each strand of a DNA double helix will act as sense and antisense in different regions. Topologists like to note that the juxtaposition of the 3′ end of one DNA strand beside the 5′ end of the other at both ends of a double-helical segment makes the arrangement a crab canon.

In some viruses DNA appears in a non-helical, single-stranded form. Because many of the DNA repair mechanisms of cells work only on paired bases, viruses that carry single-stranded DNA genomes mutate more frequently than they would otherwise. As a result, such species may adapt more rapidly to avoid extinction. The result would not be so favorable in more complicated and more slowly replicating organisms, however, which may explain why only viruses carry single-stranded DNA. These viruses presumably also benefit from the lower cost of replicating one strand versus two.

[Harley Scarow]

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. 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. Working in the 19th century, biochemists initially isolated DNA and RNA from cell nuclei. They were relatively quick to appreciate the polymeric nature of their nucleic acid isolates, but realized only later that nucleotides were of two types--one containing ribose and the other deoxyribose. It was this subsequent discovery that led to the identification and naming of DNA as a substance distinct from RNA. Friedrich Miescher 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 and 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. Max Delbrück, Nikolai V. Timofeeff-Ressovsky, and Karl G. Zimmer published results in 1935 suggesting that chromosomes are very large molecules the structure of which can be changed by treatment with X-rays, and that by so changing their structure it was possible to change the heritable characteristics governed by those chromosomes. In 1937 William Astbury produced the first X-ray diffraction patterns from DNA. He was not able to propose the correct structure but the patterns showed that DNA had a regular structure and therefore it might be possible to deduce what this structure was. In 1943, Oswald Theodore Avery and a team of scientists discovered that traits proper to the smooth form of the Pneumococcus could be transferred to the "rough" form of the same bacteria merely by making the killed smooth form available to the live rough form. Quite unexpectedly, the living R Pneumococcus bacteria were transformed into a new strain of the S form, and the transferred S characteristics turned out to be heritable. Avery called the medium of transfer of traits the transforming principle; he identified DNA as the transforming principle, and not protein as previously thought. He essentially redid Fredrick Griffith’s experiment. In 1953, Alfred Hershey and Martha Chase did an experiment that showed, in T2 phage, that DNA is the genetic material. Francis Crick's first sketch of the deoxyribonucleic acid double-helix pattern. In 1944, the renowned physicist, Erwin Schrödinger, published a brief book entitled What is Life?, where he maintained that chromosomes contained what he called the hereditary code-script" of life. He added: "But the term code-script is, of course, too narrow. The chromosome structures are at the same time instrumental in bringing about the development they foreshadow. They are law-code and executive power to use another simile, they are architect's plan and builder's craft -- in one. He conceived of these dual functional elements as being woven into the molecular structure of chromosomes. By understanding the exact molecular structure of the chromosomes one could hope to understand both the architect's plan and also how that plan was carried out through the builder's craft. Three groups took up Schrödinger's challenge to work out the structure of the chromosomes and the question of how the segments of the chromosomes that were conceived to relate to specific traits could possibly do their jobs. Just how the presence of specific features in the molecular structure of chromosomes could produce traits and behaviors in living organisms was unimaginable at the time. Because chemical dissection of DNA samples always yielded the same four nucleotides, the chemical composition of DNA appeared simple, perhaps even uniform. Organisms, on the other hand, are fantastically complex individually and widely diverse collectively. Geneticists did not speak of genes as conveyors of "information" in such words, but if they had, they would not have hesitated to quantify the amount of information that genes need to convey as vast. The idea that information might reside in a chemical in the same way that it exists in text--as a finite alphabet of letters arranged in a sequence of unlimited length--had not yet been conceived. It would emerge upon the discovery of DNA's structure, but few researchers imagined that DNA's structure had much to say about genetics. In the 1950s, three groups made it their goal to determine the structure of DNA. The first group to start was at King's College London and was led by Maurice Wilkins and was later joined by Rosalind Franklin. Another group consisting of Francis Crick and James D. Watson was at Cambridge. A third group was at Caltech and was led by Linus Pauling. Crick and Watson built physical models using metal rods and balls, in which they incorporated the known chemical structures of the nucleotides, as well as the known position of the linkages joining one nucleotide to the next along the polymer. At King's College Maurice Wilkins and Rosalind Franklin examined X-ray diffraction patterns of DNA fibers. Of the three groups, only the London group was able to produce good quality diffraction patterns and thus produce sufficient quantitative data about the structure.

In 1948 Pauling discovered that many proteins included helical shapes. Pauling had deduced this structure from X-ray patterns. Even in the initial diffraction data from DNA by Maurice Wilkins, it was evident that the structure involved helices. But this insight was only a beginning. There remained the questions of how many strands came together, whether this number was the same for every helix, whether the bases pointed toward the helical axis or away, and ultimately what were the explicit angles and coordinates of all the bonds and atoms. Such questions motivated the modeling efforts of Watson and Crick. In their modeling, Watson and Crick restricted themselves to what they saw as chemically and biologically reasonable. Still, the breadth of possibilities was very wide. A breakthrough occurred in 1952, when Erwin Chargaff visited Cambridge and inspired Crick with a description of experiments Chargaff had published in 1947. Chargaff had observed that the proportions of the four nucleotides vary between one DNA sample and the next, but that for particular pairs of nucleotides -- adenine and thymine, guanine and cytosine -- the two nucleotides are always present in equal proportions. Watson and Crick had begun to contemplate double helical arrangements, but they lacked information about the amount of twist and the distance between the two strands. Rosalind Franklin had to disclose some of her findings for the Medical Research Council and Crick saw this material through Max Perutz's links to the MRC. Franklin's work confirmed a double helix that was on the outside of the molecule and also gave an insight into its symmetry, in particular that the two helical strands ran in opposite directions. Watson and Crick were again greatly assisted by more of Franklin's data. This is controversial because Franklin's critical X-ray pattern was shown to Watson and Crick without Franklin's knowledge or permission. Wilkins showed the famous Photo 51 to Watson at his lab immediately after Watson had been unsuccessful in asking Franklin to collaborate to beat Pauling in finding the structure. From the data in photograph 51 Watson and Crick were able to discern that not only was the distance between the two strands constant, but also to measure its exact value of 2 nanometres. The same photograph also gave them the 3.4 nanometre-per-10 bp "pitch" of the helix. The final insight came when Crick and Watson saw that a complementary pairing of the bases could provide an explanation for Chargaff's puzzling finding. However the structure of the bases had been incorrectly guessed in the textbooks as the enol tautomer when they were more likely to be in the keto form. When Jerry Donohue pointed this fallacy out to Watson, Watson quickly realised that the pairs of adenine and thymine, and guanine and cytosine were almost identical in shape and so would provide equally sized rungs between the two strands. With the base-pairing, the Watson and Crick quickly converged upon a model, which they announced before Franklin herself had published any of her work.Franklin was two steps away from the solution. She had not guessed the base-pairing and had not appreciated the implications of the symmetry that she had described. However she had been working almost alone and did not have regular contact with a partner like Crick and Watson, and with other experts such as Jerry Donohoe. Her notebooks show that she was aware both of Jerry Donohue's work concerning tautomeric forms of bases and of Chargaff's work.The disclosure of Franklin's data to Watson has angered some people who believe Franklin did not receive due credit at the time and that she might have discovered the structure on her own before Crick and Watson. In Crick and Watson's famous paper in Nature in 1953, they said that their work had been stimulated by the work of Wilkins and Franklin, whereas it had been the basis of their work. However they had agreed with Wilkins and Franklin that they all should publish papers in the same issue of Nature in support of the proposed structure. Watson and Crick's model attracted great interest immediately upon its presentation. Arriving at their conclusion on February 21, 1953, Watson and Crick made their first announcement on February 28. Their paper 'A Structure for Deoxyribose Nucleic Acid' was published on April 25. In an influential presentation in 1957, Crick laid out the "Central Dogma", which foretold the relationship between DNA, RNA, and proteins, and articulated the sequence hypothesis. A critical confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 in the form of the Meselson-Stahl experiment. Work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of codons, and Har Gobind Khorana and others deciphered the genetic code not long afterward. These findings represent the birth of molecular biology. Watson, Crick, and Wilkins were awarded the 1962 Nobel Prize for Physiology or Medicine for discovering the molecular structure of DNA, by which time Franklin had died from cancer, at the age of 37. Nobel prizes are not awarded posthumously; had she lived, the difficult decision over whom to jointly award the prize would have been complicated as the prize can only be shared between two or three.

That is what DNA’s characteristics, discovery, and advances show. Hard to believe that all of DNA is what makes animals like us and others in nature, pretty strange that DNA is what controls how we act, don’t you think?

[Harley Scarow]

RNA (Ribonucleic Acid)

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Ribonucleic acid (RNA) is a nucleic acid polymer consisting of covalently bound nucleotides. RNA nucleotides contain ribose rings and uracil unlike deoxyribonucleic acid, which contains deoxyribose and thymine. It is transcribed from DNA by enzymes called RNA polymerases and further processed by other enzymes. RNA serves as the template for translation of genes into proteins, transferring amino acids to the ribosome to form proteins, and also translating the transcript into proteins.

Johann Friedrich Miescher, who called the material nuclein since it was found in the nucleus, discovered nucleic acids in 1869. It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis had been suspected since 1939, based on experiments carried out by Torbjörn Caspersson, Jean Brachet and Jack Schultz. The sequence of the 77 nucleotides of yeast tRNA was found by Robert W. Holley in 1964, winning Holley the 1968 Nobel Prize for Medicine.

RNA is primarily made up of four different bases: adenine, guanine, cytosine, and uracil. The first three are the same as those found in DNA, but uracil replaces thymine as the base complementary to adenine. This base is also a pyrimidine and is very similar to thymine. Uracil is energetically less expensive to produce than thymine, which may account for its use in RNA. In DNA, however, uracil is readily produced by chemical degradation of cytosine, so having thymine as the normal base makes detection and repair of such incipient mutations more efficient. Thus, uracil is appropriate for RNA, where quantity is important but lifespan is not, whereas thymine is appropriate for DNA where maintaining sequence with high fidelity is more critical. There are also numerous modified bases found in RNA that serve many different roles. Pseudouridine and the DNA base thymidine are found in various places. There are nearly 100 other naturally occurring modified bases, many of which are not fully understood.

Unlike DNA, RNA is almost always a single-stranded molecule and has a much shorter chain of nucleotides. RNA contains ribose, rather than the deoxyribose found in DNA. This hydroxyl group makes RNA less stable than DNA because it is more prone to hydrolysis. Several types of RNA (tRNA, rRNA) contain a great deal of secondary structure, which help promote stability.

An enzyme, RNA polymerase, using DNA as a template, usually catalyzes synthesis of RNA. Initiation of synthesis begins with the binding of the enzyme to a promoter sequence in the DNA. The DNA double helix is unwound by the helicase activity of the enzyme. The enzyme then progresses along the template strand in the 3’ -> 5’ direction, synthesizing a complementary RNA molecule with elongation occurring in the 5’ -> 3’ direction. The DNA sequence also dictates where termination of RNA synthesis will occur.

Messenger RNA is RNA that carries information from DNA to the ribosome sites of protein synthesis in the cell. Once mRNA has been transcribed from DNA, it is exported from the nucleus into the cytoplasm, where it is bound to ribosomes and translated into protein. After a certain amount of time the message degrades into its component nucleotides, usually with the assistance of RNases. Transfer RNA is a small RNA chain of about 74-93 nucleotides that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. It has sites for amino-acid attachment and an anticodon region for codon recognition that binds to a specific sequence on the messenger RNA chain through hydrogen bonding. It is a type of non-coding RNA. Ribosomal RNA (rRNA) is a component of the ribosomes, the protein synthetic factories in the cell. Eukaryotic ribosomes contain four different rRNA molecules: 18S, 5.8S, 28S, and 5S rRNA. Three of the rRNA molecules are synthesized in the nucleolus, and one is synthesized elsewhere. RRNA molecules are extremely abundant. They make up at least 80% of the RNA molecules found in a typical eukaryotic cell. RNA genes are genes that encode RNA that is not translated into a protein. The most prominent examples of RNA genes are transfer RNA (tRNA) and ribosomal RNA, both of which are involved in the process of translation. However, since the late 1990s, many new RNA genes have been found, and thus RNA genes may play a much more significant role than previously thought. In the late 1990s and early 2000, there has been persistent evidence of more complex transcription occurring in mammalian cells (and possibly others). This could point towards a more widespread use of RNA in biology, particularly in gene regulation. A particular class of non-coding RNA, micro RNA, has been found in many metazoans and clearly plays an important role in regulating other genes. Double-stranded RNA (or dsRNA) is RNA with two complementary strands, similar to the DNA found in all higher cells. DsRNA forms the genetic material of some viruses. In eukaryotes, it may play a role in the process of RNA interference and in microRNAs.

The RNA world hypothesis proposes that the earliest forms of life relied on RNA both to carry genetic information and to catalyze biochemical reactions like an enzyme. According to this hypothesis, descendents of these early lifeforms gradually integrated DNA and proteins.

Single stranded RNA molecules tend to form hydrogen bonds with itself in order to reach the minimum energy state. This leads to several recognizable "domains" of secondary structure like hairpin loops, bulges and internal loops. Secondary structure of RNA molecule can be predicted computationally by calculating free energies for different combinations of hydrogen bondings and domains. This is what and how RNA works.

[Harley Scarow]

What is a Clone?

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Cloning is the process of creating an identical copy of an original. A clone in the biological sense, therefore, is a single cell or multi-cellular organism that is genetically identical to another living organism. Sometimes this can refer to "natural" clones made either when an organism reproduces asexually or when two genetically identical individuals are produced by accident, but in common parlance the clone is an identical copy by some conscious design. Also see clone. The term clone is derived from êëùí, the Greek word for "twig". In horticulture, the spelling clon was used until the twentieth century; the final e came into use to indicate the vowel is a "long o" instead of a "short o". Since the term entered the popular lexicon in a more general context, the spelling clone has been used exclusively.

Cloning a gene means to extract a gene from one organism and insert it into a second organism, where it can be used and studied. Cloning a gene sometimes can refer to success in identifying a gene associated with some phenotype. For example, when biologists say that the gene for disease X has been cloned, they mean that the gene's location and DNA sequence has been identified, although the ability to specifically copy the physical DNA is a side-effect of its identification. A related technique called subcloning refers to transferring a gene from one plasmid into another for further study. Cloned reproductive organs have been known to be able to grow back if damaged. Cloning a cell means to derive a population of cells from a single cell. This is an important in vitro procedure when the expansion of a single cell with certain characteristics is desired, for example in the production of gene-targeted ES cells. Most individuals began as a single cell and are therefore the result of clonal expansion in vivo. Cloning an organism broadly means to create a new organism with the same genetic information as a cell from an existing one. In a modern context, this can involve somatic cell nuclear transfer in which a cell of the organism to be cloned, with its nucleus containing the DNA, is transferred into an egg cell which has had its nucleus removed. As the nucleus contains almost all of the genetic information of a lifeform, the "host" egg cell will develop into an organism with genetically identical nuclear DNA to the nucleus "donor". However, this process does not conserve the mitochondrial genome unless the nucleus and egg cell donor were the same individual. Thus, nuclear transfer clones are not clones in the strictest sense because the mitochondrial genome is not the same as that of the nucleus donor cell from which it was produced. This may have important implications for cross-species nuclear transfer in which nuclear-mitochondrial incompatibilities may lead to inviability. The first animal clone was a frog cloned by Thomas J. King and Robert W. Briggs in 1952. The term clone is used in horticulture to mean all descendants of a single plant, produced by vegetative reproduction. Many horticultural varieties of plants are clones, having been derived from a single individual, multiplied by some process other than sexual reproduction. As an example, some European varieties of grapes represent clones that have been propagated for over two millennia. Other such examples are potatoes or bananas. Also grafting can be regarded as cloning, since all the shoots and branches coming from the graft are genetically a clone of a single individual. These are genuine examples of cloning in the broader biological sense, as they create genetically identical organisms by biological means, but this particular kind of cloning has not come under ethical scrutiny and is generally treated as an entirely different kind of operations. Cloning exists in nature in some species and is referred to as parthenogenesis. An example is the "Little Fire Ant," Wasmannia auropunctata, which is native to Central and South America but has spread throughout many tropical environments. In this species, circumstantial evidence from microsatellite DNA suggests that both queens and males may reproduce clonally in one population in Suriname.

Here are the species cloned so far: Tadpole, carp, sheep, rhesus monkey, cattle, cat, mule, horse, human, and a dog. These are all of the animals cloned so far, as more will be made in the future by scientists.

Christian views of cloning are diverse and sometimes conflicting. Roman Catholicism and other conservative Christian denominations believe that the soul enters the body at the moment of conception when the sperm and egg unite. They feel harvesting cells for embryonic cloning is tantamount to live human experimentation and contrary to God's will. Further, they maintain that producing cloned zygotes that are unlikely to survive is tantamount to murder. Some Christian conservatives express concern that cloned embryos would have no soul, since it was, in their view, born outside of God's parameters. Other Christian traditions like the United Church of Christ do not believe a fertilized ovum constitutes a person. They believe that cloning can be conducted ethically in order to help treat disease and improve the public health. Now, libertarian views on the subject suggest that it is in a person's constitutional rights to conduct this process, similar to abortion.

However, the success rate has been very low: Dolly was born after 276 failed attempts; 70 calves have been created from 9,000 attempts and one third of them died young; Prometea took 328 attempts, and, more recently, Paris Texas was created after 400 attempts. Notably, although the first clones were frogs, no adult cloned frog has yet been produced from a somatic adult nucleus donor cell. A surprising development to do with aging resulted from finds that Dolly was apparently subject to accelerated aging. Aging of this type is thought to be due to telomeres, regions at the tips of chromosomes which prevent genetic threads fraying every time a cell divides. Over time telomeres get worn down until cell-division is no longer possible - this is thought to be a cause of aging. However, when researchers cloned cows they appeared to age more slowly than expected. Analysis of the cow's telomeres showed they had not only been 'reset' to birth-length, but they were actually longer - suggesting these clones would live longer life spans than normal cows. Researchers think that this could eventually be developed to reverse aging in humans, provided that this is based chiefly on shortening of telomeres. Although some work has been performed on telomeres and aging in nuclear transfer clones, the evidence is contradictory and does not support any generalizable link. Dolly died in the year of 2003. Therapeutic cloning is the procedure for creating stem cells genetically compatible with the patient. Therapeutic cloning might provide a way to grow organs in host carrier, which become completely compatible with the original. Host carrier growing poses a risk of trans-species diseases if the host is of a different species. In human beings, this is a highly controversial issue, as it involves creating human embryos in vitro and then destroying them to obtain multipotent embryonic stem cells.

Human cloning is the creation of a genetically identical copy of an existing, or previously existing human or growing cloned tissue from that individual. The term is generally used to refer to artificial human cloning; human clones in the form of identical twins are commonplace, with their cloning occurring during the natural process of reproduction.

Cloning, or more precisely, the reconstruction of functional DNA from extinct species has, for decades, been a dream of some scientists. The possible implications of this were dramatized in the novel by Michael Crichton and high budget Hollywood thriller, "Jurassic Park". In real life, one of the most anticipated targets for cloning was once the Woolly mammoth, but attempts to extract DNA from frozen mammoths have been unsuccessful, though a Japanese team is currently working toward this goal. In 2000, a cow named Bessie gave birth to a cloned Asian gaur, an endangered species, but the calf died after 2 days; the attempt to clone a banteng was more successful and provided hope that similar techniques (using surrogate mothers of another species) might be used to clone extinct species; in anticipation of this possibility, the last bucardo, a Pyrenean ibex, was frozen immediately after it died (from illness after birth). Researchers are also considering cloning endangered species such as the giant panda, ocelot, and cheetah. See the discussion under "Dolly" for a discussion of the promises and limitations of this approach. In 2002, geneticists at the Australian Museum announced that they had replicated DNA of the Thylacine, extinct about 65 years previous, using polymerase chain reaction (PCR). However, on February 15, 2005 the museum announced that it was stopping the project after tests showed the specimens' DNA had been too badly degraded by the preservative. Most recently, on May 15, 2005, it was announced that the project would be revived, with new participation from researchers in New South Wales and Victoria. One of the continuing obstacles in the attempt to clone extinct species is the need for nearly perfect DNA. Cloning from a single specimen could not create a viable breeding population in sexually reproducing animals. Furthermore, even if males and females could be cloned, the question would remain open if they would be viable at all in the absence of parents that teach or show them natural behavior. Essentially, even if cloning an extinct species would succeed - it must be considered that cloning still is an experimental technology that succeeds only by chance -, it is far more likely than not that any resulting animals, even if they were healthy, would be little more than curios or museum pieces. Most conservation biologists are rather vehemently opposed to cloning and consider it a smokescreen fit for generating headlines, but detrimental to conservation success, as funds needed to preserve habitat and wild populations threaten to be diverted to such cloning projects and eventually might even cause the extinction of species in a wild state; the rule-of-thumb in animal conservation is that conservation attempts in captivity are not to be undertaken on a standalone basis if it is still feasible to conserve habitat and viable wild populations. The banteng cloning project was an exception, as the animal cloned was a distinct genetic lineage and the value of preserving this piece of genetic diversity of an already inbred species outweighed the uncertainties.

Dolly, an ewe, was the first mammal to have been successfully cloned from an adult cell. She was cloned at the Roslin Institute in Scotland and lived there until her death when she was 6. Her birth was announced on 22 February 1997. Ian Wilmut is the leader of the research team who created Dolly. The name "Dolly" came from a suggestion by Jesse Haase who helped with her birth, in honour of Dolly Parton, because it was a mammary cell that was cloned. The technique that was made famous by her birth is somatic cell nuclear transfer, in which a non-reproductive cell containing a nucleus is placed in a de-nucleated ovum (which then develops into a fetus). When Dolly was cloned in 1996 from a cell taken from a six-year-old ewe, she became the centre of much controversy that still exists today. On 9 April 2003 her stuffed remains were placed at Edinburgh's Royal Museum, part of the National Museums of Scotland.

While the promise of cloning extinct species has been a long standing justification for the development of cloning, there are many other applications, such as cloning animals, which appears to offer a much faster and more efficient way of propagating desirable genes than traditional breeding. Another application which has recently become feasible is the cloning of pets. The company Genetic Savings and Clone was established to provide such a service, using chromatid transfer which is arguably more effective than nuclear transfer, with Little Nicky being the first pet cloned by the company after the death of the original cat. The procedure is still very expensive and has little demand. However, demand could be generated from unexpected quarters, such as Hollywood movies studios, which could seek to store genetic samples of "animal actors" for the purpose of creating a clone to replace the original animal in a sequel. Since cloning is a costly business, only the people who are more economically successful can clone either themselves or have genetically modified children, usually what we call "Designer Babies". Consquently, this has the potential to create a division of human society: The rich who are genetically enhanced or who own backup clones of themselves, and the rest of mankind. Human cloning is currently prohibited. Cloning is quite inefficient and usually there are over 600 to 1000 nuclear transfers before one is able to grow into a stem cell. This inefficiency is thought to be due to genetic imprinting in the cloned adult cell that interferes with the correct gene expression in the embryo. Even those animals that are successfully cloned are not as heathly as the original animal. For example, Dolly had arthritis and sign of premature aging. Cloning and Stem Cells, published by Mary Ann Liebert, Inc., publishes peer-reviewed research papers on the remarkable new opportunities in medicine, biology, and agriculture that arise from the demonstration of far greater than expected developmental plasticity in mammalian cells. Papers cover all aspects of cloning along with the culture and differentiation of stem cells from all stages of development from embryo to adult.

Cloning is something that may seem like science-fiction only, but it’s indeed something that actually exists. Not all is known about cloning, but we know that it is something that is very mysterious, as it may someday be used for the good of mankind…or rather goes out of control and destroy mankind.