What Is Genetics?

Genetics is the science of genes, heredity, and the variation of organisms. Humans began applying knowledge of genetics in prehistory with the domestication and breeding of plants and animals. In modern research, genetics provides important tools in the investigation of the function of a particular gene, e.g. analysis of genetic interactions. Within organisms, genetic information generally is carried in chromosomes, where it is represented in the chemical structure of particular DNA molecules.

Genes encode the information necessary for synthesizing proteins, which, in turn play a large role in influencing, although, in many instances, do not completely determine, the final phenotype of the organism. The phrase to code for is often used to mean a gene contains the instructions on how to build a particular protein, as in the gene codes for the protein. Note that the "one gene, one protein" concept is now known to be simplistic. For example, a single gene may produce multiple products, depending on how its transcription is regulated.

Areas of genetics Classical genetics Main articles: Classical genetics, Mendelian inheritance

Classical genetics consists of the techniques and methodologies of genetics that predate the advent of molecular biology. After the discovery of the genetic code and such tools of cloning as restriction enzymes, the avenues of investigation open to geneticists were greatly broadened. Some classical genetic ideas have been supplanted with the mechanistic understanding brought by molecular discoveries, but many remain intact and in use, such as the Mendel's laws.

Molecular genetics Main article: Molecular genetics

Molecular genetics builds upon the foundation of classical genetics but focuses on the structure and function of genes at a molecular level. Molecular genetics employs the methods of both classical genetics (such as hybridization) and molecular biology. It is so-called to differentiate it from other sub fields of genetics such as ecological genetics and population genetics. An important area within molecular genetics is the use of molecular information to determine the patterns of descent, and therefore the correct scientific classification of organisms: this is called molecular systematics. The study of inherited features not strictly associated with changes in the DNA sequence is called epigenetics.

Some take the view that life can be defined, in molecular terms, as the set of strategies which RNA polynucleotides have used and continue to use to perpetuate themselves. This definition grows out of work on the origin of life, specifically the RNA world hypothesis.

Population, quantitative and ecological genetics Main articles: Population genetics, Quantitative genetics, Ecological genetics

Population, quantitative and ecological genetics are all very closely related subfields and also build upon classical genetics (supplemented with modern molecular genetics). They are chiefly distinguished by a common theme of studying populations of organisms drawn from nature but differ somewhat in the choice of which aspect of the organism on which they focus. The foundational discipline is population genetics which studies the distribution of and change in allele frequencies of genes under the influence of the four evolutionary forces: natural selection, genetic drift, mutation and migration. It is the theory that attempts to explain such phenomena as adaptation and speciation.

The related subfield of quantitative genetics, which builds on population genetics, aims to predict the response to selection given data on the phenotype and relationships of individuals. A more recent development of quantitative genetics is the analysis of quantitative trait loci. Traits that are under the influence of a large number of genes are known as quantitative traits, and their mapping to a location on the chromosome requires accurate phenotypic, pedigree and marker data from a large number of related individuals.

Ecological genetics again builds upon the basic principles of population genetics but is more explicitly focused on ecological issues. While molecular genetics studies the structure and function of genes at a molecular level, ecological genetics focuses on wild populations of organisms, and attempts to collect data on the ecological aspects of individuals as well as molecular markers from those individuals.

Genomics Main article: Genomics

A more recent development is the rise of genomics, which attempts the study of large-scale genetic patterns across the genome for (and in principle, all the DNA in) a given species.

Closely-related fields The science which grew out of the union of biochemistry and genetics is widely known as molecular biology. The term "genetics" is often widely conflated with the notion of genetic engineering, where the DNA of an organism is modified for some kind of practical end, but most research in genetics is aimed at understanding and explaining the effect of genes on phenotypes and in the role of genes in populations (see population genetics and ecological genetics), rather than genetic engineering.

History It was not until 1865 that Gregor Mendel first traced inheritance patterns of certain traits in pea plants and showed that they obeyed simple statistical rules. Although not all features show these patterns of Mendelian inheritance, his work acted as a proof that application of statistics to inheritance could be highly useful. Since that time many more complex forms of inheritance have been demonstrated.

From his statistical analysis Mendel defined a concept that he described as an allele, which was the fundamental unit of heredity. The term allele as Mendel used it is nearly synonymous with the term gene, whilst the term allele now means a specific variant of a particular gene.

The significance of Mendel's work was not understood until early in the twentieth century, after his death, when his research was re-discovered by other scientists working on similar problems.

Mendel was unaware of the physical nature of the gene. We now know that genetic information is normally carried on DNA. (Certain viruses store their genetic information in RNA). Manipulation of DNA can in turn alter the inheritance and features of various organisms.

Timeline of notable discoveries:

1859 Charles Darwin publishes The Origin of Species

1865 Gregor Mendel's paper, Experiments on Plant Hybridization

1903 Chromosomes are discovered to be hereditary units

1905 British biologist William Bateson coins the term "genetics" in a letter to Adam Sedgwick

1910 Thomas Hunt Morgan shows that genes reside on chromosomes

1918 Ronald Fisher publishes On the correlation between relatives on the supposition of Mendelian inheritance - the modern synthesis starts.

1913 Gene maps show chromosomes containing linear arranged genes

1927 Physical changes in genes are called mutations

1928 Frederick Griffith discovers a hereditary molecule that is transmissible between bacteria (see Griffiths experiment)

1931 Crossing over is the cause of recombination

1941 Edward Lawrie Tatum and George Wells Beadle show that genes code for proteins; see the original central dogma of genetics

1944 Oswald Theodore Avery, Colin McLeod and Maclyn McCarty isolate DNA as the genetic material (at that time called transforming principle)

1950 Erwin Chargaff shows that the four nucleotides are not present in nucleic acids in stable proportions, but that some general rules appear to hold (e.g., that the amount of adenine, A, tends to be equal to that of thymine, T).

1952 The Hershey-Chase experiment proves the genetic information of phages (and all other organisms) to be DNA

1953 DNA structure is resolved to be a double helix by James D. Watson and Francis Crick

1958 The Meselson-Stahl experiment demonstrates that DNA is semiconservatively replicated

1961 The genetic code is arranged in triplets

1977 DNA is sequenced

1997 First genome sequenced

2001 First draft sequences of the human genome are released simultaneously by the Human Genome Project and Celera Genomics.

2003 (14 April) Successful completion of Human Genome Project with 99% of the genome sequenced to a 99.99% accuracy

Genes are material entities that parents pass to offspring during reproduction. These entities encode information essential for the construction and regulation of polypeptides, proteins and other molecules that determine the growth and functioning of the organism.

The word "gene" is shared by many disciplines, including classical genetics, molecular genetics, evolutionary biology and population genetics. Because each discipline models the biology of life differently, the material entity that supports the gene in one discipline is not the same as in the other.

Following the discovery that DNA is the genetic material, and with the growth of biotechnology and the project to sequence the human genome, the common usage of the word "gene" has increasingly reflected its meaning in molecular biology. In the molecular-biological sense, genes are the segments of DNA which cells transcribe into RNA and translate, at least in part, into proteins.

In common speech, "gene" is often used to refer to the hereditary cause of a trait, disease or condition—as in "the gene for obesity." Speaking more precisely, a biologist might refer to an allele or a mutation that has been implicated in or is associated with obesity. This is because biologists know that many factors other than genes decide whether a person is obese or not: prenatal environment, upbringing, culture and the availability of food, for example.

Moreover, it is very unlikely that variations within a single gene—or single genetic locus—fully determine one's genetic predisposition for obesity. These aspects of inheritance—the interplay between genes and environment, the influence of many genes—appear to be the norm with regard to many and perhaps most ("complex" or "multifactoral") traits. The term phenotype refers to the characteristics that result from this interplay (see genotype-phenotype distinction).

Properties of genes In molecular biology, the DNA of a gene encodes the chemical structure of a protein. The genetic code determines the sequence of the amino acids that make up a protein. The coding of a three nucleotide DNA sequence to a specific amino acid is essentially the same for all known life, from bacteria to humans.

Through the proteins they encode, genes govern the cells in which they reside. In multicellular organisms they control the development of the individual from the fertilized egg and the day-to-day functions of the cells that make up tissues and organs. The instrumental roles of their protein products range from mechanical support of the cell structure to the transportation and manufacture of other molecules and to the regulation of other proteins' activities.

The genes that exist today are those that have reproduced successfully in the past. Often, many individual organisms share a gene; thus, the death of an individual need not mean the extinction of the gene. Indeed, if the sacrifice of one individual enhances the survivability of other individuals with the same gene, the death of an individual may enhance the overall survival of the gene. This is the basis of the selfish gene view, popularized by Richard Dawkins. He points out in his book, The Selfish Gene, that to be successful genes need have no other "purpose" than to propagate themselves, even at the expense of their host organism's welfare. A human that behaved in such a way would be described as "selfish," although ironically a selfish gene may promote altruistic behaviors. According to Dawkins, the possibly disappointing answer to the question "what is the meaning of life?" may be "the survival and perpetuation of ribonucleic acids and their associated proteins".

Types of genes Due to rare, spontaneous errors (e.g. in DNA replication) mutations in the sequence of a gene may arise. Once propagated to the next generation, this mutation may lead to variations within a species' population. Variants of a single gene are known as alleles, and differences in alleles may give rise to differences in traits, for example eye color. A gene's most common allele is called the wild type allele, and rare alleles are called mutants.

Normally, RNA is an intermediate product in the translation of a molecular gene into a protein. However, for some gene sequences, RNA molecules are actually the functional end products. For example, RNAs known as ribozymes are capable of enzymatic function, or small interfering RNAs have a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA, or RNA genes.

All living organisms carry their genes and transmit them to offspring as DNA, but some viruses carry only RNA. Because they use RNA, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription. On the other hand, RNA retroviruses, such as AIDS, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized.

In the early 1900s, Mendel's work received renewed attention from scientists. In 1910, Thomas Hunt Morgan showed that genes reside on specific chromosomes. He later showed that genes occupy specific locations on the chromosome. With this knowledge, Morgan and his students began the first chromosomal map of Drosophila. In 1928, Frederick Griffith showed that genes could be transferred. In what is now known as Griffith's experiment, injections into a mouse of a deadly strain of a bacteria that had been heat-killed transferred genetic information to a safe strain of the same bacteria, killing the mouse.

In 1941, George Wells Beadle and Edward Lawrie Tatum showed that mutations in genes caused errors in certain steps in metabolic pathways. This showed that specific genes code for specific proteins, leading to the "one gene, one enzyme" hypothesis. Oswald Avery, Collin Macleod, and Maclyn McCarty showed in 1944 that DNA holds the gene's information. In 1953, James D. Watson and Francis Crick demonstrated the molecular structure of DNA. Together, these discoveries established the central dogma of molecular biology, which states that proteins are transcribed from RNA which is translated from DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses.

Heredity (the adjective is hereditary) is the transfer of characters from parent to offspring, either through their genes or through the social institution called inheritance (for example, a title of nobility is passed from individual to individual according to relevant customs and/or laws).

Biology In biology, heredity refers to the transference of biological characteristics from a parent organism to offspring, and is practically a homonym for genetics, as genes are now recognized as the carriers of biological information. In humans, defining which characteristics of a final person are due to heredity and which are due to environmental influences is often a site of controversy (the nature versus nurture debate), especially regarding intelligence and race.

Genetic interactions, in genetics, are interactions that occur between two or more mutations that results in a new phenotype. Studying genetic interactions can reveal gene function, the nature of the mutations, functional redundancy, and protein interactions. Because protein complexes are responsible for most biological functions, genetic interactions are a powerful tool.

The phenotype of an individual organism is either its total physical appearance and constitution, or a specific manifestation of a trait, such as size or eye color, that varies between individuals. Phenotype is determined to some extent by genotype, or by the identity of the alleles that an individual carries at one or more positions on the chromosomes. Many phenotypes are determined by multiple genes and influenced by environmental factors. Thus, the identity of one or a few known alleles does not always enable prediction of the phenotype.

Nevertheless, because phenotypes are much easier to observe than genotypes (it doesn't take chemistry or sequencing to determine a person's eye color), classical genetics uses phenotypes to deduce the functions of genes. These inferences can then be checked by breeding experiments. In this way, early geneticists were able to trace inheritance patterns without any knowledge whatsoever of molecular biology.

The interaction between genotype and phenotype has often been described using a simple equation:

Phenotype = Genotype + Environment That is a phenotype is any detectable characteristics of an organism (i.e. structural, biochemical, physiological and behavioural) determined by an interaction between its genotype and environment (see genotype-phenotype distinction for a further elaboration of this distinction).

The idea of the phenotype as the product of the genotype has been generalised by Richard Dawkins in his book The Extended Phenotype.

The genotype is the specific genetic makeup (the specific genome) of an individual, usually in the form of DNA. It codes for the phenotype of that individual.

Typically, one refers to an individual's genotype with regard to a particular gene of interest and, in polyploid individuals, it refers to what combination of alleles the individual carries (see homozygous, heterozygous). Any given gene will usually cause an observable change in an organism, known as the phenotype. The terms genotype and phenotype are distinct for at least two reasons:

To distinguish the source of an observer's knowledge (one can know about genotype by observing DNA; one can know about phenotype by observing outward appearance of an organism). Genotype and phenotype are not always directly correlated. Some genes only express a given phenotype in certain environmental conditions. Conversely, some phenotypes could be the result of multiple genotypes. Inspired by the biological concept and usefulness of genotypes, computer science employs simulated genotypes in genetic programming and evolutionary algorithms. Such techniques can help evolve mathematical solutions to certain types of otherwise difficult problems.

The genotype-phenotype distinction refers to the fact that while genotype and phenotype of an organism are related, they do not necessarily coincide. The genotype of an organism represents its exact genetic makeup, that is, the particular set of genes it possesses. Two organisms whose genes differ at even one locus (position in their genome) are said to have different genotypes. The term "genotype" refers, then, to the full hereditary information of an organism. The phenotype of an organism, on the other hand, represents its actual physical properties, such as height, weight, hair color, and so on. The mapping of a set of genotypes to a set of phenotypes is sometimes referred to as the genotype-phenotype map.

An organism's genotype is the largest influencing factor in the development of its phenotype, but it is not the only one. Even two organisms with identical genotypes normally differ in their phenotypes. One experiences this in everyday life with monozygous (i.e. identical) twins. Identical twins share the same genotype, since their genomes are identical; but they never have the same phenotype, although their phenotypes may be very similar. This is apparent in the fact that their mothers and close friends can always tell them apart, even though others might not be able to see the subtle differences. Further, identical twins can be distinguished by their fingerprints, which are never completely identical.

The concept of phenotypic plasticity describes the degree to which an organism's phenotype is determined by its genotype. A high level of plasticity means that environmental factors have a strong influence on the particular phenotype that develops. If there is little plasticity, the phenotype of an organism can be reliably predicted from knowledge of the genotype, regardless of environmental peculiarities during development. An example of high plasticity can be observed in larval newts1 when these larvae sense the presence of predators such as dragonflies, they develop larger heads and tails relative to their body size and display darker pigmentation. Larvae with these traits have a higher chance of survival when exposed to the predators, but grow more slowly than other phenotypes.

In contrast to phenotypic plasticity, the concept of genetic canalization addresses the extent to which an organism's phenotype allows conclusions about its genotype. A phenotype is said to be canalized if mutations (changes in the genome) do not noticeably affect the physical properties of the organism. This means that a canalized phenotype may form from a large variety of different genotypes, in which case it is not possible to exactly predict the genotype from knowledge of the phenotype. If canalization is not present, small changes in the genome have an immediate effect on the phenotype that develops.

Classical genetics consists of the techniques and methodologies of genetics that predate the advent of molecular biology. A key disocvery of classical genetics in eukaryotes, was genetic linkage. The observation that some genes do not segregate independently at meiosis, broke the laws of Mendelian inheritance, and provided science with a way to map characteristics to a location on the chromosomes. Linkage maps are still used today, especially in breeding for plant improvement.

After the discovery of the genetic code and such tools of cloning as restriction enzymes, the avenues of investigation open to geneticists were greatly broadened. Some classical genetic ideas have been supplanted with the mechanistic understanding brought by molecular discoveries, but many remain intact and in use. Classical genetics is often contrasted with reverse genetics, and aspects of molecular biology are sometimes referred to as molecular genetics.

Genetic linkage occurs when particular alleles are inherited together. Typically, an organism can pass on a allele without regard to which allele was passed on for a different gene. This is because chromosomes are sorted randomly during meiosis. However, alleles which are on the same chromosome more likely to be inherited together and are said to be linked.

Because there is some crossing over of DNA when the chromosomes segregate, alleles on the same chromosome can be separated and go to different cells. There is much more chance of this happening if the alleles are far apart on the chromosome, as it is more likely that a cross-over will occur between them.

The physical distance between two genes can be calculated using the offspring of an organism showing two linked genetic traits, and finding the percentage of children where the two traits don't run together. The higher the percentage of offspring that don't show both traits, the further apart on the chromosome they are. A study of the linkages between many genes enables the creation of a linkage map.

Two phenotypes (height and texture) occur randomly with respect to one another in a manner known as independent assortment. Today scientists understand that independent assortment occurs when the genes affecting the phenotypes are found on different chromosomes.

An exception to independent assortment develops when genes appear near one another on the same chromosome. When genes occur on the same chromosome, they are inherited as a single unit. Genes inherited in this way are said to be linked. For example, in fruit flies the genes affecting eye color and wing length are inherited together because they appear on the same chromosome.

Human gene nomenclature. For each known human gene the HUGO Gene Nomenclature Committee (HGNC) approve a gene name and symbol (short-form abbreviation). All approved symbols are stored in Genew, the Human Gene Nomenclature Database. Each symbol is unique and each gene is only given one approved gene symbol. It is necessary to provide a unique symbol for each gene so that people can talk about them. This also facilitates electronic data retrieval from publications. In preference each symbol maintains parallel construction in different members of a gene family and can also be used in other species, especially the mouse. k, f. Estimates of the number of genes in an organism are somewhat controversial, because it is only possible to discover a gene, and no techniques currently exist to prove that a DNA sequence contains no gene. Nonetheless, estimates are made based on current knowledge.

But in many cases, genes on the same chromosome that are inherited together produce offspring with unexpected allele combinations. This results from a process called crossing over. Sometimes at the beginning of meiosis, a chromosome pair (made up of a chromosome from the mother and a chromosome from the father) may intertwine and exchange sections of chromosome. The pair then breaks apart to form two chromosomes with a new combination of genes that differs from the combination supplied by the parents. Through this process of recombining genes, organisms can produce offspring with new combinations of maternal and paternal traits that may contribute to or enhance survival.

An allele is any one of a number of alternative forms of the same gene occupying a given locus (position) on a chromosome. An example is the gene for blossom color in many species of flower - a single gene controls the color of the petals, but there may be several different versions of the gene. One version might result in red petals, while another might result in white petals.

Some organisms are diploid - that is, they have paired homologous chromosomes in their somatic cells, and thus contain two copies of each gene. An organism in which both copies of the gene are identical - that is, have the same allele - is said to be homozygous for that gene. An organism which has two different alleles of the gene is said to be heterozygous. Often one allele is "dominant" and the other is "recessive" - the "dominant" allele will determine what trait is expressed. For example, in the case of blossom color, if the "red" allele is dominant to the "white" allele, in a heterozygous flower (with one red and one white allele), the petals will be red. The recessive allele will only be expressed in a recessive homozygote.

One exception is incomplete dominance. Another exception is "codominance", where both alleles are active and both traits are expressed; for example, both red and white petals. Codominance is also apparent in human blood types. A gene containing the codominant pure blood type alles "AA" and "BB" would result in a blood type of "AB". A third exception is "blending inheritance", present in flower blossoms as well. Codominant "blue" and "purple" alleles would result in color blending and hence, violet flower petals.

A wild type allele is an allele which is considered to be "normal" for the organism in question, as opposed to a mutant allele which is usually a relatively new modification.

A chromosome is, minimally, a very long, continuous piece of DNA, which contains many genes, regulatory elements and other intervening nucleotide sequences. In the chromosomes of eukaryotes, the uncondensed DNA exists in a quasi-ordered structure inside the nucleus, where it wraps around histones (structural proteins, Fig. 1), and where this composite material is called chromatin. During mitosis (cell division), the chromosomes are condensed and called metaphasic chromosomes. This is the only natural context in which individual chromosomes are visible with an optical microscope. Prokaryotes do not possess histones or nuclei. a, l, g. In its relaxed state, the DNA can be accessed for transcription, regulation, and replication. Chromosomes were first observed by Karl Wilhelm von Nägeli in 1842 and their behavior later described in detail by Walther Flemming in 1882. In 1910, Thomas Hunt Morgan proved that chromosomes are the carriers of genes.

Eukaryotes possess multiple linear chromosomes contained in the cell's nucleus. Each chromosome has one centromere, with one or two arms projecting from the centromere. The ends of the chromosomes are special structures called telomeres. DNA replication begins at many different locations on the chromosome.

Chromosomes in bacteria Bacterial chromosomes are often circular but sometimes linear. Some bacteria have one chromosome, while others have a few. Bacterial DNA also exists as plasmids. The distinction between plasmids and chromosomes is poorly defined, though size and necessity are generally taken into account. Bacterial chromosomes initiate replication and one origin of replication.

Chromatin Two types of chromatin can be distinguished:

Euchromatin, which consists of DNA that is active, e.g., expressed as protein. Heterochromatin, which consists of mostly inactive DNA. It seems to serve structural purposes during the chromosomal stages. Heterochromatin can be further distinguished into two types: Constitutive heterochromatin, which is never expressed. It is located around the centromere and usually contains repetitive sequences. Facultative heterochromatin, which is sometimes expressed.

In the early stages of mitosis, the chromatin strands become more and more condensed. They cease to function as accessible genetic material and become a compact transport form. Eventually, the two matching chromatids (condensed chromatin strands) become visible as a chromosome, linked at the centromere. Long microtubules are attached at the centromere and two opposite ends of the cell. During mitosis, the microtubules pull the chromatids apart, so that each daughter cell inherits one set of chromatids. Once the cells have divided, the chromatids are uncoiled and can function again as chromatin. In spite of their appearance, chromosomes are highly structured (Fig. 2). For example, genes with similar functions are often kept close together in the nucleus, even if they are far apart on the chromosome. The short arm of a chromosome can be extended by a satellite chromosome that contains codes for ribosomal RNA.

Normal members of a particular species all have the same number of chromosomes (Table 1). Asexually reproducing species have one set of chromosomes, which is the same in all body cells. Sexually reproducing species have somatic cells (body cells), which are diploid [2n] (they have two sets of chromosomes, one from the mother, one from the father) or polyploid [Xn] (more than two sets of chromosomes), and gametes (reproductive cells) which are haploid [n] (they have only one set of chromosomes). Gametes are produced by meiosis of a diploid germ line cell. During meiosis, the matching chromosomes of father and mother can exchange small parts of themselves (crossover), and thus create new chromosomes that are not inherited solely from either parent. When a male and a female gamete merge (fertilization), a new diploid organism is formed.

To determine the (diploid) number of chromosomes of an organism, cells can be locked in metaphase in vitro (in a reaction vial) with colchicine. These cells are then stained (the name chromosome was given because of their ability to be stained), photographed and arranged into a karyotype (an ordered set of chromosomes, Fig. 3), also called karyogram. Like many sexually reproducing species, humans have special gonosomes (sex chromosomes, in contrast to autosomes for body functions). These are XX in females and XY in males. In females, one of the two X chromosomes is inactive and can be seen under a microscope as Barr bodies.

Chemical structure of a gene Four kinds of sequentially linked nucleotides compose a DNA molecule or strand (more at DNA). These four nucleotides constitute the genetic alphabet. A sequence of three consecutive nucleotides, called a codon, is the protein-coding vocabulary. The sequence of codons in a gene specifies the amino-acid sequence of the protein it encodes. In most eukaryotic species, very little of the DNA in the genome encodes proteins, and the genes may be separated by vast sequences of so-called junk DNA. a, c, f, k, l. Moreover, the genes are often fragmented internally by non-coding sequences called introns, which can be many times longer than the genes themselves. Introns are removed on the heels of transcription by splicing. In the primary molecular sense they represent parts of a gene, however.

Deoxyribonucleic acid (DNA) is a nucleic acid which carries genetic instructions for the biological development of all cellular forms of life and many viruses. DNA is sometimes referred to as the molecule of heredity as it is inherited and used to propagate traits. During reproduction, it is replicated and transmitted to offspring.

In bacteria and other simple cell organisms, DNA is distributed more or less throughout the cell. In the complex cells that make up plants, animals and in other multi-celled organisms, most of the DNA is found in the chromosomes, which are located in the cell nucleus. The energy-generating organelles known as chloroplasts and mitochondria also carry DNA, as do many viruses.

Although sometimes called "the molecule of heredity", pieces of DNA as people typically think of them are not single molecules. Rather, they are pairs of molecules, which entwine like vines to form a double helix (see the illustration at the right).

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 four kinds of Aromatic hydrocarbon "bases". Because DNA strands are composed of these nucleotide subunits, they are polymers.

The diversity of the bases means that there are four kinds of nucleotides, which are commonly referred to by the identity of their bases. These are adenine (A), thymine (T), cytosine (C), and guanine (G).

In a DNA double helix, two polynucleotide strands can associate through the hydrophobic effect. 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 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, and 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.

The role of the sequence Within a gene, the sequence of nucleotides along a DNA strand defines a protein, which 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 (eg. ACT, CAG, TTT). These codons can then be translated with messenger RNA and then transfer RNA, with a codon corresponding to a particular amino acid. Since there are 64 possible codons, most amino acids have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region.

In many species of organism, only a small fraction of the total sequence of the genome appears to encode protein. 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.

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 Main article: DNA replication

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 can result in a less than perfect copy (see mutation), 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, replication and termination.

Mechanical properties relevant to biology

Space-filling model of a section of DNA moleculeThe 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 (10 kilobase pairs, or 10 kbp). 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 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 helix makes one complete turn about its axis. This frequency of twist (known as the helical pitch) depends largely on stacking forces that each base exerts on its neighbors in the chain.

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 5 centimetres long for strands in a human chromosome. 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.

The B form of the DNA helix twists 360° per 10.6 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.

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 those used in crystallography 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.

DNA sequence reading 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 (the "ascending strand"), and the other way along the other strand (the "descending strand"). This arrangement of the strands is called antiparallel.

All the genes and intervening DNA together make up the genome of an organism, which in many species is divided among several chromosomes and typically present in two or more copies. The location (or locus) of a gene and the chromosome on which it is situated is in a sense arbitrary. Genes that appear together on the chromosomes of one species, such as humans, may appear on separate chromosomes in another species, such as mice. e, h, b, f, e. Two genes positioned near one another on a chromosome may encode proteins that figure in the same cellular process or in completely unrelated processes. As an example of the former, many of the genes involved in spermatogenesis reside together on the Y chromosome.

For reasons of chemical nomenclature, people who work with DNA refer to the asymmetric termini of each strand as the 5' and 3' ends (pronounced "five prime" and "three prime"). DNA workers and enzymes alike always read nucleotide sequences in the "5' to 3' direction". 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.

Some viruses blur the distinction between sense and antisense, because 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.

Topologists like to note that the juxtaposition of the 3' end of one DNA strand beside the 5' end of the other at both termini of a double-helical segment makes the arrangement a "crab canon".

Single-stranded DNA (ssDNA) and repair of mutations 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.

The discovery of DNA and the double helix Working in the 19th century, biochemists initially isolated DNA and RNA (mixed together) 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 (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.

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. (Delbrück and Salvador Luria were awarded the Nobel Prize in 1969 for their work on the genetic structure of viruses.) In 1943, Oswald Theodore Avery 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" (S) form available to the live "rough" (R) 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.

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 -- or, 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." Francis Crick, James D. Watson, Maurice Wilkins, Rosalind Franklin, Seymour Benzer, et al., took up the physicist'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.

Many species carry more than one copy of their genome within each of their somatic cells. These organisms are called diploid if they have two copies, or polyploid if they have more than two copies. In such organisms, the copies are practically never identical. With respect to each gene, the copies that an individual possesses are liable to be distinct alleles, which may act synergistically or antagonistically to generate a trait or phenotype. The ways that gene copies interact are explained by chemical dominance relationships (more at genetics, allele). Expression of molecular genes For various reasons, the relationship between DNA strand and a phenotype trait is not direct. j, l, c, f, b. The same DNA strand in 2 different individuals may result in different traits because of the effect of other DNA strands or the environment.

In the 1950s, only a few groups made it their goal to determine the structure of DNA. These included an American group led by Linus Pauling, and two groups in Britain. At the University of Cambridge, Crick and Watson were building 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, London, Maurice Wilkins and Rosalind Franklin were examining x-ray diffraction patterns of DNA fibers.

A key inspiration in the work of all of these teams was the discovery in 1948 by Pauling that many proteins included helical (see alpha helix) shapes. Pauling had deduced this structure from x-ray patterns. Even in the initial crude diffraction data from DNA, 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, and they saw that by reversing the directionality of one strand with respect to the other, they could provide an explanation for Chargaff's puzzling finding. This explanation was the complementary pairing of the bases, which also had the effect of ensuring that the distance between the phosphate chains did not vary along a sequence. Watson and Crick were able to discern that this distance was constant and to measure its exact value of 2 nanometres from an X-ray pattern obtained by Franklin. The same pattern also gave them the 3.4 nanometre-per-10 bp "pitch" of the helix. The pair quickly converged upon a model, which they announced before Franklin herself published any of her work.

The great assistance Watson and Crick derived from Franklin's data has become a subject of controversy, and it has angered people who believe Franklin has not received the credit due to her. The most controversial aspect is that Franklin's critical X-ray pattern was shown to Watson and Crick without Franklin's knowledge or permission. Wilkins showed it to them at his lab while Franklin was away.

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' 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 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 Medicine for discovering the molecular structure of DNA, by which time Franklin had died. Nobel prizes are not awarded posthumously.

A DNA sequence (sometimes genetic sequence) is a succession of letters representing the primary structure of a real or hypothetical DNA molecule or strand, The possible letters are A, C, G, and T, representing the four nucleotide subunits of a DNA strand (adenine, cytosine, guanine, thymine), and typically these are printed abutting one another without gaps, as in the sequence AAAGTCTGAC. This coded sequence is sometimes referred to as genetic information. A succession of any number of nucleotides greater than four is liable to be called a sequence. With regard to its biological function, which may depend on context, a sequence may be sense or anti-sense (see DNA), and either coding or noncoding. DNA sequences can also contain "junk DNA".

When a sequence motif appears in the exon of a gene, it may encode the "structural motif" of a protein; that is a stereotypical element of the overall structure of the protein. Nevertheless, motifs need not be associated with a distinctive secondary structure. "Noncoding" sequences are not translated into proteins and nucleic acids with such motifs need not deviate from the typical shape (e.g. the "B-form" DNA double helix).

Outside of gene exons, there exist regulatory sequence motifs and motifs within the "junk," such as satellite DNA. Some of these are believed to affect the shape of nucleic acids (see for example RNA self-splicing), but this is only sometimes the case. For example, many DNA binding proteins that have affinities for specific motifs only bind DNA in its double-helical form. They are able to recognize motifs through contact with the double helix's major or minor groove.

Short coding motifs, which appear to lack secondary structure, include those that label proteins for delivery to particular parts of a cell, or mark them for phosphorylation.

Within a sequence or database of sequences, researchers search and find motifs using computer-based techniques of sequence analysis, such as BLAST. Such techniques belong to the discipline of bioinformatics.

See also: consensus sequence.

Motif bioinformatics Consider the N-glycosylation site motif mentioned above:

Asn, followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro This pattern may be written as N{P}[ST]{P} where N=Asn, P=Pro, S=Ser, T=Thr; {X} means any amino acid except X; and [XY] means either X or Y.

The notation [XY] does not give any indication of the probability of X or Y occurring in the pattern. Sometimes patterns are defined in terms of a probabilistic model such as a hidden Markov model.

Motifs and consensus sequences The notation [XYZ] means X or Y or Z, but does not indicate the likelihood of any particular match. For this reason, two or more patterns are often associated with a single motif: the defining pattern, and various typical patterns.

For example, the defining sequence for the IQ motif may be taken to be:

[FILV]Qxxx[RK]Gxxx[RK]xx[FILVWY] where x signifies any amino acid, and the square brackets indicate an alternative (see below for further details about notation).

Usually, however, the first letter is I, and both [RK] choices resolve to R. Since the last choice is so wide, the pattern IQxxxRGxxxR is sometimes equated with the IQ motif itself, but a more accurate description would be a consensus sequence for the IQ motif.

The DNA strand is expressed into a trait only if it is transcribed to RNA. Because the transcription starts from a specific base-pair sequence (a promoter) and stops at another (a terminator), our DNA strand needs to be correctly placed between the two. If not, it is considered as junk DNA, and is not expressed. Cells regulate the activity of genes in part by increasing or decreasing their rate of transcription. Over the short term, this regulation occurs through the binding or unbinding of proteins, known as transcription factors, to specific non-coding DNA sequences called regulatory elements. So, to be expressed, our DNA strand needs to be properly regulated by other DNA strands. the DNA strand may also be silenced through DNA methylation or by chemical changes to the protein components of chromosomes (see histone). This is a permanent form of regulation of the transcription. the RNA is often edited before its translation into a protein. Eukaryotic cells splice the transcripts of a gene, by keeping the exons and removing the introns. So, the DNA strand needs to be in an exon to be expressed. Because of the complexity of the splicing process, one transcribed RNA may be spliced in alternate ways to produce not one but a variety of proteins (alternative splicing) from one pre-mRNA. g, h, j, a, g. Prokaryotes produce a similar effect by shifting reading frames during translation. the translation of RNA into a protein also starts with a specific start and stop sequence. once produced, the protein interacts with the many other proteins in the cell, according to the cell metabolism. This interaction finally produces the trait.

Software There are software programs which, given multiple input sequences, attempt to identify one or more candidate motifs. One example is MEME, which generates statistical information for each candidate.

Discovery through evolutionary conservation Motifs have been discovered by studying similar genes in different species. For example, by aligning the amino acid sequences specified by the GCM (glial cells missing) gene in man, mouse and D. melanogaster, Akiyama and others discovered a pattern which they called the GCM motif. It spans about 150 amino acid residues, and begins as follows:

WDIND*.*P..*...D.F.*W***.**.IYS**...A.*H*S*WAMRNTNNHN Here each . signifies a single amino acid or a gap, and each * indicates one member of a closely-related family of amino acids.

The authors were able to show that the motif has DNA binding activity.

In genetics, transcription is the process of copying DNA to RNA by an enzyme called RNA polymerase (RNAP).

Ribonucleic acid (RNA) is a nucleic acid consisting of a string of covalently-bound nucleotides. It is biochemically distinguished from DNA by the presence of an additional hydroxyl group, attached to each pentose ring; as well as by the use of uracil, instead of thymine. RNA transmits genetic information from DNA (via transcription) into proteins (by translation).

RNA has 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 may be because uracil is energetically less expensive to produce, although it easily degenerates into cytosine. Thus, uracil is appropriate for RNA, where quantity is important but lifespan is not, whereas thymine is appropriate for DNA.

Comparison to DNA Structurally, RNA is indistinguishable from DNA except for the critical presence of a hydroxyl group attached to the pentose ring in the 2' position (DNA has a hydrogen atom rather than a hydroxyl group). This hydroxyl gives the molecule far greater catalytic versatility and allows it to perform reactions that DNA is incapable of performing; but at the same time, it makes RNA sensitive to alkaline hydrolysis, to which DNA is not.

The other major difference between RNA and DNA is that RNA is almost exclusively found in the single-stranded form (an exception being the genetic material of some kinds of viruses). RNA molecules often fold into more complex structures by making use of complementary internal sequences; that is, one part of a single RNA molecule is the nucleic acid complement of another part of the same molecule (for example, 5'-ACUCGA-3' and 5'-UCGAGU-3'), so that the two strands bind together. This allows the formation of hairpin loops, coils, etc., which then direct the formation of higher-order structures.

Synthesis RNA is made by an enzyme, RNA polymerase, using DNA as a template. The synthesis begins when the enzyme binds special promoter regions in the DNA. The DNA double helix is unwound by the helicase activity of the enzyme. RNA is then synthesised so that it is complementary to one of strands in the DNA. A small stretch of DNA-RNA hybrid is present at the active site of the enzyme. The synthesis continues until a termination sequence is reached. The resulting RNA molecule is the primary transcript. Modulation of the rate of initiation of RNA synthesis is one of the most important ways in which gene expression is regulated.

RNA world hypothesis The RNA world hypothesis proposes that the universal ancestor to all life relied on RNA both to carry genetic information like DNA and to catalyze biochemical reactions like an enzyme. In effect, RNA was, before the emergence of the first cell, the dominant, and probably the only, form of life. This hypothesis is inspired by the fact that retroviruses use RNA as their sole genetic material, while peptide bond formation in the ribosome is carried out by an RNA-derived ribozyme. From this perspective, retroviruses and ribozymes are remnants, or molecular fossils, left over from that RNA world. Assuming that DNA is better suited for storage of genetic information and proteins are better suited for the catalytic needs of cells, one would expect reduced use of RNA in cells, and greater use of DNA and proteins.

Messenger RNA (mRNA) Main article: Messenger RNA

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 (in eukaryotes mRNA is "processed" before being exported), 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.

Non-coding RNA or "RNA genes" Main article: Non-coding RNA

RNA genes (sometimes referred to as non-coding RNA or small RNA) 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 (rRNA), 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.

Double-stranded RNA 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.

In biology, mitosis is the process of chromosome segregation and nuclear division that follows replication of the genetic material in eukaryotic cells. This process assures that each daughter nucleus receives a complete copy of the organism's genome. In most eukaryotes mitosis is accompanied with cell division or cytokinesis, but there are many exceptions, for instance among the fungi. There is another process called meiosis, in which the daughter nuclei receive half the chromosomes of the parent, which is involved in gamete formation and other similar processes.

Mitosis is divided into several stages, with the remainder of the cell's growth cycle considered interphase. Properly speaking, a typical cell cycle involves a series of stages: G1, the first growth phase; S, where the genetic material is duplicated; G2, the second growth phase; and M, where the nucleus divides through mitosis. Mitosis is divided into prophase, prometaphase, metaphase, anaphase, and telophase.

Plasmids are (typically) circular double stranded DNA molecules that are separate from the chromosomal DNA (Fig. 1). They usually occur in bacteria, sometimes in eukaryotic organisms (e.g., the 2-micrometre-ring in Saccharomyces cerevisiae). Their size varies from 1 to over 400 kilo base pairs (kbp). There are from one copy, for large plasmids, to hundreds of copies of the same plasmid present in a single cell.

This complex process helps explain the different meanings of "gene": a nucleotide sequence in a DNA strand; or the transcribed RNA, prior to splicing; or the transcribed RNA after splicing, i.e. without the introns The latter meaning of gene is the result of more "material entity" that the first one. Mutations and evolution Just as there are many factors influencing the expression of a particular DNA strand, there are many ways to have genetic mutations. For example, natural variations within regulatory sequences appear to underlie many of the heritable characteristics seen in organisms. The influence of such variations on the trajectory of evolution through natural selection may be as large as or larger than variation in sequences that encode proteins. a, l, d, j, i. Thus, though regulatory elements are often distinguished from genes in molecular biology, in effect they satisfy the shared and historical sense of the word. Indeed, a breeder or geneticist, in following the inheritance pattern of a trait, has no immediate way to know whether this pattern arises from coding sequences or regulatory sequences. Typically, he or she will simply attribute it to variations within a gene.

Plasmid often contain genes or gene-cassettes that confer a selective advantage to the bacterium harboring them, e.g., the ability to build an antibiotic resistance. Every plasmid contains at least one DNA sequence that serves as an origin of replication or ori (a starting point for DNA replication), which enables the plasmid DNA to be duplicated independently from the chromosomal DNA.

Plasmids that exist only as a single copy in each bacterium are, upon cell division, in danger of being lost in one of the segregating bacteria. Such single-copy plasmids have systems which attempt to actively distribute a copy to both daughter cells.

Some plasmids include an addiction system. They produce both a long-lived poison and its short-lived antidote. The cell that keeps a copy of the plasmid will survive, while the cell without the plasmid will die because it is running out of antidote shortly. This is an example of plasmids as selfish DNA.

Applications of plasmids Plasmids serve as important tools in genetics and biochemistry labs, where they are commonly used to multiply (make many copies of) or express particular genes. There are many plasmids that are commercially available for such uses. Initially, the gene to be replicated is inserted in a plasmid . These plasmids contain, in addition to the inserted gene, one or more genes capable of providing antibiotic resistance to the bacteria that harbors them. The plasmids are next inserted into bacteria by a process called transformation, which are then grown on specific antibiotic(s). Bacteria which took up one or more copies of the plasmid then express (make protein) the gene that confers antibiotic resistance. This is typically a protein which can break down any antibiotics that would otherwise kill the cell. As a result, only the bacteria with antibiotic resistance can survive, the very same bacteria containing the genes to be replicated. The antibiotic(s) will, however, kill those bacteria that did not receive a plasmid, because they have no antibiotic resistance genes. In this way the antibiotic(s) acts as a filter selecting out only the modified bacteria. Now these bacteria can be grown in large amounts, harvested and lysed to isolate the plasmid of interest.

Another major use of plasmids is to make large amounts of proteins. In this case you grow the bacteria containing a plasmid harboring the gene of interest. Just as the bacteria produces proteins to confer its antibiotic resistance, it can also be induced to produce large amounts of proteins from the inserted gene. This is a cheap and easy way of mass-producing a gene or the protein it then that codes for--for example, insulin or even antibiotics.

A bacterial artificial chromosome (BAC) is a DNA construct, based on a fertility plasmid, used for transforming and cloning in bacteria, usually E. coli. Its usual insert size is 150 kbp, with a range from 100 to 300 kbp.

BACs are often used in sequencing other organisms, in genome projects, for example the Human Genome Project. A short piece of the organisms DNA is amplified as an insert in BACs, then sequenced. Finally, the sequenced parts are rearranged in silico, resulting in the genome sequence of the sequenced organism.

In genetics terminology, sequencing is most often restricted to determining the nucleotides of a DNA or RNA strand. Currently, most such sequencing is performed using the chain termination method; however, this can only be used to identify fairly short sequences (around 300-1000 base pairs on ABI machine), and must therefore be used as the basis for more complex techniques, such as chromosome walking and shotgun sequencing.

The genetic code is a set of rules, which maps DNA sequences to proteins in the living cell, and is employed in the process of protein synthesis. Nearly all living things use the same genetic code, called the standard genetic code, although a few organisms use minor variations of the standard code.

The genetic information carried by an organism - its genome - is inscribed in a DNA molecule. Each functional portion of this molecule is referred to as a gene. Each gene is transcribed into a short template molecule of the related polymer RNA, which is better suited for protein synthesis. This in turn is translated, by mediation of a machinery consisting of ribosomes and a set of transfer RNAs and associated enzymes, into an amino acid chain (polypeptide).

The gene sequence inscribed in DNA, and thus in RNA, is composed of units called codons, each coding for an amino acid, hence the phrase genetic code. The polypeptide is ultimately folded into a 3-dimensional protein structure, which will go on to perform some specific function in the cell such as an enzyme subunit or cell membrane component. This chain of events involving RNA transcription, and polypeptide translation is referred to as gene expression. Some genes encode other elements such as ribosomal RNAs and transfer RNAs, both of which are involved in protein synthesis.

Both DNA and RNA are comprised of 4 nucleotide bases. In the case of DNA this is comprised of adenine (A), guanine (G), cytosine (C) and thymine (T). RNA is identical with the exception that thymine (T) is substituted with uracil (U). Codons are non-overlapping groups of the three bases. There are 43 = 64 codons. For example, the RNA sequence UUUAAACCC contains the codons UUU, AAA and CCC, each of which specifies one amino acid. So, this RNA sequence represents a protein sequence, three amino acids long. (DNA is also a sequence of nucleotide bases, but there thymine takes the place of uracil.)

In classical genetics, the stop codons were given names: UAG was amber, UGA was opal, and UAA was ocher. These names were originally the names of the specific genes in which mutation of each of these stop codons was first detected. Translation starts with a chain initiation codon (start codon). But unlike stop codons, these are not sufficient to begin the process; nearby initiation sequences are also required to induce transcription into mRNA and binding by ribosomes. The most notable start codon is AUG, which also codes for methionine. CUG and UUG, and in prokaryotes GUG and AUU, also work.

Errors during DNA replication may lead to the duplication of a gene, which may diverge over time. Though the two sequences may remain the same or be only slightly altered, they are typically regarded as separate genes (i.e. not as alleles of the same gene). The same is true when duplicate sequences appear in different species. Yet, though the alleles of a gene differ in sequence, nevertheless they are regarded as a single gene (occupying a single locus). History The existence of genes was first suggested by Gregor Mendel, who studied inheritance in pea plants and hypothesized a factor that conveys traits from parent to offspring. h, l, c, e, i. Although he did not use the term gene, he explained his results in terms of inherited characteristics. Mendel was also the first to hypothesize independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the difference between what would later be described as genotype and phenotype. Mendel's concept was finally named when Wilhelm Johannsen coined the word gene in 1909.

Many codons are redundant; i.e., two codons may code for the same amino acid. This redundancy is typically confined to the third position, e.g. both GAA and GAG code for the amino acid glutamine. A codon is said to be four-fold degenerate if any nucleotide at its third position specifies the same amino acid; it is said to be two-fold degenerate if only two of four possible nucleotides at its third position specify the same amino acid. In two-fold degenerate codons, the equivalent third position nucleotides are always either two purines (A/G) or two pyrimidines (C/T).

These properties of the genetic code make it more fault-tolerant for mutations. For example, four-fold degenerate codons can tolerate any mutation at the third position; two-fold degenerate codons can tolerate one out of the three possible mutations at the third position. Since transition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine to pyrimidine or vice-versa) mutations, the equivalence of purines or that of pyrimidines at two-fold degenerate sites adds a further fault-tolerance.

These variable codes for amino acids are possible because of modified bases in the first base of the anticodon, and the basepair formed is called a wobble base pair. The modified bases include inosine and the U-G basepair.

Only two amino acids are specified by a single codon; one of these is the amino-acid methionine, specified by the codon AUG, which also specifies the start of transcription; the other is tryptophan, specified by the codon UGG.

Origin of the genetic code Numerous variations of the standard genetic code are found in mitochondria, energy-burning organelles. Ciliate protozoa also have some variation in the genetic code: UAG and often UAA code for Glutamine (a variant also found in some green algae), or UGA codes for Cysteine. Another variant is found in some species of the yeast candida, where CUG codes for Serine. In some species of bacteria and archaea, a few non-standard amino acids are substituted for standard stop codons; UGA can code for selenocysteine and UAG can code for pyrrolysine. There may be other non-standard amino acids and codon interpretations that are not known.

Despite these variations, the genetic codes used by all known forms of life on Earth are very similar. Since there are many possible genetic codes that are thought to have similar utility to the one used by Earth life, the theory of evolution suggests that the genetic code was established very early in the history of life.

One can ask the question: is the genetic code completely random, just one set of codon-amino acid correspondences that happened to establish itself and be "frozen in" early in evolution, although functionally any other of the near-infinite set of possible transcription tables would have done just as well? Already a cursory look at the table shows patterns that suggest that this is not the case.

Recent aptamer experiments have shown, that amino acids have indeed a selective chemical affinity for the base triplets that code for them. This suggests, that the current, complex transcription mechanism involving tRNA and associated enzymes is a later development, and that originally, protein sequences were directly templated on base sequences. Also, evidence has been found originally the number of different amino acids used may have been considerably smaller than today.

Molecular genetics is the field of biology which studies the structure and function of genes at a molecular level. Molecular genetics employs the methods of genetics and molecular biology. It is so-called to differentiate it from other sub fields of genetics such as ecological genetics and population genetics. An important area within molecular genetics is the use of molecular information to determine the patterns of descent, and therefore the correct scientific classification or organisms: this is called molecular systematics.

Forward genetics One of the first tools available to molecular geneticists is the forward genetic screen. The aim of this technique is to identify mutations that produce a certain phenotype. A mutagen is very often used to accelerate this process. Once mutants have been isolated, the mutated gene can be molecularly identified.

Reverse genetics Main article: Reverse genetics

While forward genetic screens are productive, a more straightforward approach would be to determine the phenotype that results from mutating a given gene. This is called reverse genetics. In some organisms, such as yeast and mice, it is possible to induce the deletion of a particular gene, creating a gene knockout. Alternatives include the random induction of DNA deletions and subsequent selection for deletions in a gene of interest, the application of RNA interference and the creation of transgenic organisms that overexpress a gene of interest.

Since the late 1950s and early 1960s, molecular biologists have learned to characterise, isolate, and manipulate the molecular components of cells and organisms. These components include DNA, the repository of genetic information; RNA, a close relative of DNA whose functions range from serving as a temporary working copy of DNA to actual structural and enzymatic functions as well as a functional and structural part of the translational apparatus; and proteins, the major structural and enzymatic type of molecule in cells.

Expression cloning One of the most basic techniques of molecular biology to study protein function is expression cloning. In this technique, DNA coding for a protein of interest is cloned (using PCR and/or restriction enzymes) into a plasmid (known as an expression vector). This plasmid may have special promoter elements to drive production of the protein of interest, and may also have antibiotic resistance markers to help follow the plasmid.

This plasmid can be inserted into either bacterial or animal cells. Introducing DNA into bacterial cells is called transformation, and can be effected by several methods, including electroporation, microinjection and chemically. Introducing DNA into eukaryotic cells, such as animal cells, is called transfection. Several different transfection techniques are available, including calcium phosphate transfection, liposome transfection, and proprietary transfection reagents such as Fugene. DNA can also be introduced into cells using viruses as a carrier. In such cases, the technique is called viral transduction, and the cells are said to be transduced.

In either case, DNA coding for a protein of interest is now inside a cell, and the protein can now be expressed. A variety of systems, such as inducible promoters and specific cell-signaling factors, are available to help express the protein of interest at high levels. Large quantities of a protein can then be extracted from the bacterial or eukaryotic cell. The protein can be tested for enzymatic activity under a variety of situations, the protein may be crystallized so its tertiary structure can be studied, or, in the pharmaceutical industry, the activity of new drugs against the protein can be studied.

Polymerase chain reaction (PCR) Main article: Polymerase chain reaction

The polymerase chain reaction is an extremely versatile technique for copying DNA. In brief, PCR allows a single DNA sequence to be copied (millions of times), or altered in predetermined ways. For example, PCR can be used to introduce restriction enzyme sites, or to mutate (change) particular bases of DNA. PCR can also be used to determine whether a particular DNA fragment is found in a cDNA library.

Gel electrophoresis:

Gel electrophoresis is one of the principal tools of molecular biology. The basic principle is that DNA, RNA, and proteins can all be separated using an electric field. In agarose gel electrophoresis, DNA and RNA can be separated based on size by running the DNA through an agarose gel. Proteins can be separated based on size using an SDS-PAGE gel. Proteins can also be separated based on their electric charge, using what is known as an isoelectric gel...

Western blotting and immunochemistry Main article: Western blot

Antibodies to most proteins can be created by injecting small amounts of the protein into an animal such as a mouse, rabbit, sheep, or donkey. These antibodies can be used for a variety of analytical and preprative techniques.

In Western blotting, proteins are first separated by size, in a thin gel sandwiched between two glass plates. This technique is called SDS-PAGE (for Sodium Dodecyl Sulfate Poly-Acrylamide Gel Electrophoresis). The proteins in the gel are then transferred to a PVDF, nitrocellulose, nylon or other support membrane. This membrane can then be probed with solutions of antibodies. Antibodies that specifically bind to the protein of interest can then be visualized by a variety of techniques, including chemoluminescence or radioactivity.

Antibodies can also be used to purify proteins. Antibodies to a protein are generated and are often then coupled to "beads". After the antibody has bound to the protein of interest, this antibody-protein complex can be separated from all other proteins by centrifugation. During centrifugation, the beads, to which the antibody is coupled, will pellet (bringing the protein of interest down with it) whereas all other proteins will remain in the solution. Alternatively, antibodies coupled to a solid support matrix like Sephadex or Sepharose beads, for example, can be used to remove a protein of interest from a complex solution. After washing unbound and non-specifically bound materials away from the "beads", the protein of interest is then eluted from the matrix, usually by adding a solution with a high salt concentration, or by varying the pH of the solution in which the matrix is contained. The beads can either be suspended in solution (batch processing) or packed into a tube (column processing).

A body's genetic materials can be found within the nucleus of each of its cells. These genetic materials consist of coils of deoxyribonucleic acid or what is known as DNA. They are arranged in a complex way to form chromosomes of which there are 46 in pairs in each human cell. Of these pairs of chromosomes, one is the sex chromosome. The DNA molecule is a long double helix that when looked at under a microscope would remind one of a spiral stair case. The steps of this stair case are what determines a person's genetic code. These consist of pairs of four types of molecules which are called bases. In each of these steps guanine is paired with cytosine while thymine is paired with adenine. A person's genetic code is written in triplets, thus each step of the staircase codes the production of only one of the amino acids. These amino acids are the building blocks for proteins.

At any given time, when a part of the DNA molecule is controlling a function of the cell, its helix will split open along its length with one strand being inactive while the other strand acts as a template for a complementary strand of ribonucleic acid or RNA to form. The bases for the RNA are arranged in the same sequence as the bases of the inactive strand of DNA with the exception of the fact that RNA contains uracil and DNA contains thymine. This copy, which is called messenger RNA, will separate from the DNA leaving the nucleus and traveling into the cytoplasm of the cell. It then attaches to ribosomes which are the cell's factories for making proteins and instructs the ribosome as to the sequence of amino acids that are needed to construct a specific protein. These amino acids are brought to the ribosome by what are known as transfer RNA which is a much smaller type of RNA. Each molecule of the transfer RNA will bring one amino acid to be used in the growing chain of protein.

Each gene consists of a code that is needed to construct one protein. Depending on the size of the protein the genes will vary in size. All genes are arranged in a precise sequence on the chromosomes with the location of a specific gene called its locus. It is the two sex chromosomes that determine if a fetus will become male or female. Females will have two X chromosomes with only one being active while the male will have one X and one Y sex chromosomes. Since the Y chromosome carries very genes, one of which determines sex, in males all the genes on the X chromosome whether recessive or dominant are expressed. The genes on the X chromosome are called sex-linked or X- linked genes.

It is not uncommon for a person to have abnormalities of one or more gene and especially the recessive genes. Each human carries six to eight abnormal recessive genes but these genes do not cause cells to function abnormally except when two similar recessive genes are present. Generally the chance of a person having two similar recessive genes is minute but in the case of children of close relatives the chance becomes higher. This is also true with groups of people who inter-marry. The genetic make up of a person is known as a genotype. The expression of the genotype is known as the phenotype. Each inherited trait of a person is encoded by genes. In most cases characteristics such as hair color is not considered abnormal but any abnormal characteristics express by an abnormal gene can lead to hereditary disease.

Genetics is the study of what make up an animals or plants.DNA carries all the information needed for protein synthesis and replication of cells. In living organisms DNA is organized in chromosomes and is located in the nucleus of each cell. DNA is comprised in the parts shown The Phosphate links the sugar and base together There are 4 Bases, C, G, A, T these stand for cytosine, guanine, adenine and tymine respectively. Because DNA is comprised as a double helix the bases pair up. A and T pair up and C and G there are no other possible combinations of DNA bases. For DNA to be useful it first must be transcribed into mRNA, then translated into an amino acid. This is what makes up GENES.

Genes are found on chromosomes inside a cell. Chromosomes have two sides. One contains genes from your mother (grey) and the other side genes from your father (black). These chromosomes are identical and carry the same genes in the same place. However they may carry different form of a gene. For example part of the chromosomes codes for eye colour, your father’s gene might code for blue eyes while your mother’s codes for brown. Both show eye colour just different colours. The different forms of the genes are known as alleles.

When organisms reproduce the offspring tend to resemble their parents. They are not, however, identical to either parent, and they are not simply a mixture of the two parents.

For instance, in humans one parent is male and the other female, and their children are either male or female, not a mixture of the two traits. On the other hand a child might have her father’s eye colour, and her mother’s hair colour.

Genetics is concerned with explaining the behaviour of such inherited characteristics, in terms of the underlying genetic machinery which turns a single cell (the fertilised egg) into a worm, a carrot, or a human. So genetics explains how like begets like. It also explains how, over longer time scales, living things change, or evolve, to produce the dazzling diversity of life.

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Last modified: May 25, 2005