3 - DNA.docx

DNA From Wikipedia, the free encyclopedia For a non-technical introduction to the topic, see Introduction to genetics. For other uses, see DNA (disambiguation). The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structure of two base pairs are shown in the bottom right. The structure of part of a DNA double helix Deoxyribonucleic acid (i/diˈɒksiˌraɪboʊnjʊˌkliːɪk, -ˌkleɪɪk/;[1] DNA) is a molecule that carries most of the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA and RNA are nucleic acids; alongside proteins and complex carbohydrates (polyre essential for all known forms of life. Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix. The two DNA strands are known as polynucleotides since they are composed of simpler uni).[4] DNA stores biological information. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information. Biological information is replicated as the two str, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes biological information. Under the genetic code, rocess called transcription. Within cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts.[5] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones cand Francis Crick in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the s and helicases · 4.2.3Polymerases · 5Genetic recombination · 6Evolution · 7Uses in technology · 7.1Genetic engineering · 7.2DNA profiling · 7.3DNA enzymes or catalytic DNA · 7.4Bioinformatics · 7.5DNA nanotechnology · 7.6History and anthropology · 7.7Information storage · 8History of DNA research · 9See also · 10References · 11Further reading · 12External links Properties Chemical structure of DNA; hydrogen bondsshown as dotted lines DNA is a long polymer made from repeating units called nucleotides.[7][8] The structure of DNA is non-static,[9] all species comprises two helical chains each coiled round the same axis, and each/phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs withthymine and guanine pairs with cytosine. It was represented by A-T base pairs and G-C base pairs.[19][20] Nucleobase clae pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or hand specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.[8] Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Nwn as dashed lines. The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable thngest for G,C stacks. The two strands can come apart – a process known as melting – to form two single-stranded DNA molecules (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNAcentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices witnt, making the strands easier to pull apart.[36] In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also callex melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.[37] SenseA DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.[38] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisenseiring.[40] A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes.[41] In these cases, some DNA sequences do dn read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription,[42] while in viruses, overlapping genes increase the amount of information that mall viral genome.[43] Supercoiling Further information: DNA supercoil DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helixt DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.[f highly hydrated DNA fibers in terms of squares of Bessel functions.[50] In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that thly of related DNA conformations[52] that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a signif a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsthe DNA backbone and other biomolecules.[62] Quadruplex structures Further information: G-quadruplex At the ends of the the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the c Base modifications and DNA packaging Further information: DNA methylation and Chromatin remodeling The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifn usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried oulight can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases.[79] On the other hand, oxidants such as free radicals orhydrogen peroxide produce multiple forms of damage, including base utations, insertions and deletions from the DNA sequence, as well as chromosomal translocations.[82] These mutations can cause cancer. Because of inherent limitations in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.[83][84] DNA damages that arryote nuclear DNA within the chromosomes. DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approx] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell usestion between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions betw and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequences such as promoters and enhancers, which control the transcription oe transcription of the of the open reading frame. In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences.[94] The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordiwn as the "C-value enigma".[95] However, some DNA sequences that do not code protein may still encode functional non-coding RNAmolecules, which are involved in the regulation of regulation of gene expression.[96] TRNA polymerase (blue) producing a mRNA (green) from a DNA template (orange).[97] Some noncodingsenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known cgenetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by anger RNA to transfer RNA, which carries amino acids. Since there are bases in 3-letter combinations, there are possible codons (combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' coon. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antture called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.[109][110] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence.[111] Chemical modifications strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors  transcription factors and changing the rate of transcription.[113] Other non-specific DNA-binding proteins in chromatin include best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair.[116] These binding proteins seem to stabilize single-stranded DNA an accessibility of the DNA template to the polymerase.[119] As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.[120]Conserocesses that control responses to environmental changes or cellular differentiation and development. The specificity of y of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of tA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.[123] Topoisomerases and helicases Topoisomerases are enzymes with both nuclease and ligase activitreducing its level of supercoiling; the enzyme then seals the DNA break.[45] Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.[124] Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.[46] Helicases are proteins that are a type of molecular motor. They use the chemical energy in nuck hydrogen bonds between bases and unwind the DNA double helix into single strands.[125] These enzymes are essential for most processes where enzymes need to access the DNA bases. Polymerases Polymerases are enzymes that tial that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mie, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres.[63][129] Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.[64] Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the genes in the human genome the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.[130] Gen (Cand C2). A DNA helix usually does not interact with other segments of DNA, and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".[132] This physical separa times chromosomes interact is in chromosomal crossover which occurs duringsexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin. Recombin exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selectionnatural selection and can be important in the rapid evolution of new proteins.[133] Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.[134] The most common form of chromosomal crossover is homologous recombination, where the two chromosed the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication nterstellar dust and gas clouds.[149] Uses in technology Sculpture of DNA made out of shopping carts Genetic engineering Further information: Molecular biology, Nucleic acid methods, and Genetic engineering Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratto organisms in the form of plasmids or in the appropriate format, by using a viral vector.[150] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,[1nity testing in order to determine if someone is the biologicalparent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal Dion/dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.[161]The most extensively studied class of nces and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment sequence alignment, are used in studying phylogenetic relationships and protein function.[166] Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with pr which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally.[167]Entire genomes may also be compared, which story and anthropology Further information: Phylogenetics and Genetic genealogy Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, gen Hershey–Chase experiment showed that DNA is the genetic material of the Tphage.[188] In 1953, James Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journr model of DNA was then based on a single X-ray diffraction image (labeled as "Photo 51")[189] taken by Rosalind Franklin andRaymond Gosling in May 1952, as well as the information that the DNA bases are paired. Experiment his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the should receive credit for the discovery.[193] In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between

7 - gene.docx

Gene From Wikipedia, the free encyclopedia This article is about the heritable unit for transmission of biological traits. For other uses, see Gene (disambiguation). A gene is a locus (or region) of DNA which is made up of nucleotides and is the molecular unit of heredity.[1][2]:Glossary The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. Most biological traits are under the influence ofpolygenes (many different genes) as well as the gene–environment interactions. Some genetic traits are instantly visible, such as eye colour or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemicalprocesses that comprise life. Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotype traits. Colloquial usage of the term "having a gene" (e.g., "good genes," "hair colour gene") typically refers to having a different allele of the gene. Genes evolve due to natural selection or survival of the fittest of the alleles. The concept of a gene continues to be refined as new phenomena are discovered.[3] For example, regulatory regions of a gene can be far removed from its coding regions, and coding regions can be split into several exons. Some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. Therefore, a broad, modern working definition of a gene is any discrete locus of heritable, genomic sequence which affect an organism's traits by being expressed as a functional product or byregulation of gene expression.[4][5] Contents [hide]  · 1History · 1.1Discovery of discrete inherited units · 1.2Discovery of DNA · 1.3Modern evolutionary synthesis · 2Molecular basis · 2.1DNA · 2.2Chromosomes · 3Structure and function · 3.1Functional definitions · 4Gene expression · 4.1Genetic code · 4.2Transcription · 4.3Translation · 4.4Regulation · 4.5RNA genes · 5Inheritance · 5.1Mendelian inheritance · 5.2DNA replication and cell division · 5.3Molecular inheritance · 6Molecular evolution · 6.1Mutation · 6.2Sequence homology · 6.3Origins of new genes · 7Genome · 7.1Number of genes · 7.2Essential genes · 7.3Genetic and genomic nomenclature · 8Genetic engineering · · 9See also · 10References · 10.1Main textbook · 10.2References · 10.3Further reading · 11External links History[edit] Gregor Mendel Main article: History of genetics Discovery of discrete inherited units[edit] The existence of discrete inheritable units was first suggested by Gregor Mendel (1822–1884).[6] From to 1864, he studied inheritance patterns in common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured the distinction between genotype (the genetic material of an organism) and phenotype (the visible traits of that organism). Mendel was also the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which suggested that each parent contributed fluids to the fertilisation process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan ("all, whole") and genesis ("birth") / genos ("origin").[7][8] Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction. Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th-century by Hugo de Vries, Carl Correns, and Erich von Tschermak, who (claimed to have) reached similar conclusions in their own research.[9] Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis,[10] in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" (Pangens in German), after Darwin's pangenesis theory. Sixteen years later, in 1905, the word genetics was first used by William Bateson,[11] while Eduard Strasburger, amongst others, still used the term pangene for the fundamental physical and functional unit of heredity.[12] In the Danish botanist Wilhelm Johannsen shortened the name to "gene".[13] Discovery of DNA[edit] Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA) was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s.[14][15] The structure of DNA was studied by Rosalind Franklin by Rosalind Franklin using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded le-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication.[16][17] Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since been shown to have exceptions, such as reverse transcription inretroviruses. The modern study of genetics at the level of DNA is known as molecular genetics. In 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene: the gene for Bacteriophage MScoat protein.[18] The subsequent development ofchain-termination DNA sequencing in by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool.[19] An automated version of the Sanger method was used in early phases of the Human Genome Project.[20] Modern evolutionary synthesis[edit] Main article: Modern evolutionary synthesis The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the modern evolutionary synthesis, a term introduced by Julian Huxley.[21]Evolutionary biologists subsequently refined this concept, such as George C. Williams' gene-centric view of evolution. He proposed an evolutionary concept of the gene as a unit of natural selectionwith the definition: "that which segregates and recombines with appreciable frequency."[22]:In this view, the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit. Related ideas emphasizing the centrality of genes in evolution were popularized by Richard Dawkins.[23][24] Molecular basis[edit] Main article: DNA The chemical structure of a four base pair fragment of aDNA double helix. The  sugar-phosphate backbone chains run in opposite directions with the bases pointing inwards, base-pairing A to T and C to G with hydrogen bonds. DNA[edit] The vast majority of living organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar (2'-deoxyribose), a phosphate group, and one of the fourbases adenine, cytosine, guanine, and thymine.[2]:Two chains of DNA twist around each other to form a D a DNA double helix with the phosphate-sugar backbone spiralling around the outside, and the bases pointing inwards with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form two hydrogen bonds, whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must therefore be complementary, with their sequence of bases matching such that the adenines of one strand are paired with the thymines of the other strand, and so on.[2]:Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose; this is known as the 3' end of the molecule. The other end contains an exposedphosphate group; this is the 5' end. The two strands of a double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication DNA replication and transcription occurs in the 5'→3' direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile.[25]:The expression of genes encoded in DNA begins by transcribing the gene into RNA, a second type of nucleic acid that is very similar to DNA, but whose monomers contain the sugar ribose rather thandeoxyribose. RNA also contains the base uracil in place of thymine. RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three-nucleotide sequences called codons, which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons andamino acids. The genetic code is nearly the same for all known organisms.[2]:Chromosomes[edit] Fluorescent microscopy image of a human femalekaryotype, showing pairs of chromosomes . The DNA isstained red, with regions rich in housekeeping genes further stained in green. The largest chromosomes are around times the size of the smallest.[26] The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded.[2]:The region of the chromosome at which a particular gene is located is called its locus. Each locus contains one allele of a gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence. The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome. DNA packaged and condensed in this way is calledchromatin.[2]:The manner in which DNA is stored on the histones, as well as chemical modifications of the modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression. In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division:replication origins, telomeres and the centromere.[2]:Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequence that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication. The length of the telomeres decreases each time the genome is replicated and has been implicated in the aging process.[27] The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division.[2]:Prokaryotes (bacteria and archaea) typically store their genomes on a single large, circular chromosome. Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes.[2]:Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids, which usually encode only a few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, viahorizontal gene transfer.[28] Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas the genomes of complex multicellular organisms, including humans, contain an absolute majority of DNA without an identified function.[29] This DNA has often been referred to as "junk DNA". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome, about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer.[5] Structure and function[edit] The structure of a gene consists of many elements of which the actual protein coding sequenceis often only a small part. These include DNA regions that are not transcribed as well as untranslated regions of the RNA. Firstly, flanking the open reading frame, all genes contain a regulatory sequence that is required for their expression. In order to be expressed, genes require a promoter sequence. The promoter is recognized and bound by transcription factors and RNA polymerase to initiate transcription.[2]:A gene can have more than one promoter, resulting in messenger RNAs (mRNA) that differ in how far they extend in the 5' end.[30] Promoter regions have a consensus sequence, however highly transcribed genes have "strong" promoter sequences that bind the transcription machinery well, whereas others have "weak" promoters that bind poorly and initiate transcription less frequently.[2]:Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters.[2]:Additionally, genes can have regulatory regions many kilobases upstream or downstream of the open reading frame. These act by binding to transcription factors which then cause the DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site.[31] For example, enhancers increase transcription by binding anactivator protein which then helps to recruit the RNA polymerase to the promoter; converselysilencers bind repressor proteins and make the DNA less available for RNA polymerase.[32] The transcribed pre-mRNA contains untranslated regions at both ends which contain a ribosome binding site, terminator and start and stop codons.[33] In addition, most eukaryotic open reading frames contain untranslated introns which are removed before the exons are translated. The sequences at the ends of the introns, dictate the splice sites to generate the final mature mRNAwhich encodes the protein or RNA product.[34] Many prokaryotic genes are organized into operons, with multiple protein-coding sequences that are transcribed as a unit.[35][36] The products of operon genes typically have related functions and are involved in the same regulatory network.[2]:Functional definitions[edit] Defining exactly what section of a DNA sequence comprises a gene is difficult.[3] Regulatory regions of a gene such as enhancers do not necessarily have to be close to the coding sequenceon the linear molecule because the intervening DNA can be looped out to bring the gene and its regulatory region into proximity. Similarly, a gene's introns can be much larger than its exons. Regulatory regions can even be on entirely different chromosomes and operate in trans to allow regulatory regions on one chromosome to come in contact with target genes on another chromosome.[37][38] Early work in molecular genetics suggested the model that one gene makes one protein. This model has been refined since the discovery of genes that can encode multiple proteins byalternative splicing and coding sequences split in short section across the genome whose mRNAs are concatenated by trans-splicing.[5][39][40] A broad operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products.[11] This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified asgene-associated regions.[11] Gene expression[edit] Main article: Gene expression In all organisms, two steps are required to read the information encoded in a gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA (mRNA).[2]:6.1Second, that mRNA is translated to protein.[2]:RNA-coding genes must still go through the first step, but are not translated into protein.[41] The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule is called a gene product. Genetic code[edit] Schematic of a single-stranded RNA molecule illustrating a series of three-base codons. Each three-nucleotide codon corresponds to an amino acid when translated to protein The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code. Sets of three nucleotides, known as codons, each correspond to a specific amino acid.[2]:Additionally, a "start codon", and three "stop codons" indicate the beginning and end of the protein coding region. There are possible codons (four possible nucleotides at each of three positions, hence possible codons) and only standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organismsn living organisms.[42] Transcription[edit] Transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed.[2]:The mRNA acts as an intermediate between the DNA gene and its final protein product. The gene's DNA is used as a template to generate a complementarymRNA. The mRNA matches the sequence of the gene's DNA coding strand because it is synthesised as the complement of the template strand. Transcription is performed by an enzyme called anRNA polymerase, which reads the template strand in the 3' to 5' direction and synthesizes the RNA from 5' to 3'. To initiate transcription, the polymerase first recognizes and binds a promoter region of the gene. Thus, a major mechanism of gene regulation is the blocking or sequestering the promoter region, either by tight binding by repressor molecules that physically block the polymerase, or by organizing the DNA so that the promoter region is not accessible.[2]:In prokaryotes, transcription occurs in the cytoplasm; for very long transcripts, translation may begin at the 5' end of the RNA while the 3' end is still being transcribed. In eukaryotes, transcription occurs in the nucleus, where the cell's DNA is stored. The RNA molecule produced by the polymerase is known as the primary transcript and undergoes post-transcriptional modifications before being exported to the cytoplasm for translation. One of the modifications performed is the splicing of introns which are sequences in the transcribed region that do not encode protein. Alternative splicingmechanisms can result in mature transcripts from the same gene having different sequences and thus coding for different proteins. This is a major form of regulation in eukaryotic cells and also occurs in some prokaryotes.[2]:7.5[43] Translation[edit] Protein coding genes are transcribed to an mRNAintermediate, then translated to a functional protein. RNA-coding genes are transcribed to a functional non-coding RNA. (PDB: 3BSE, 1OBB, 3TRA​) Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein.[2]:Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acidsto a growing polypeptide chain by the formation of peptide bonds. The genetic code is read three nucleotides at a time, in units calledcodons, via interactions with specialized RNA molecules called transfer RNA (tRNA). Each tRNA has three unpaired bases known as theanticodon that are complementary to the codon it reads on the mRNA. The tRNA is also covalently attached to the amino acid specified by the complementary codon. When the tRNA binds to its complementary codon in an mRNA strand, the ribosome attaches its amino acid cargo to the new polypeptide chain, which is synthesized from amino terminus to carboxyl terminus. During and after synthesis, most new proteins must folds to their active three-dimensional structure before they can carry out their cellular functions.[2]:Regulation[edit] Genes are regulated so that they are expressed only when the product is needed, since expression draws on limited resources.[2]:A cell regulates its gene expression depending on its external environment (e.g. available nutrients, temperature and other stresses), its internal environment (e.g. cell division cycle, metabolism, infection status), and its specific role if in a multicellular organism. Gene expression can be regulated at any step: from transcriptional initiation, to RNA processing, to post-translational modification of the protein. The regulation of lactose metabolism genes in E. coli (lac operon) was the first such mechanism to be described in 1961.[44] RNA genes[edit] A typical protein-coding gene is first copied into RNA as an intermediate in the manufacture of the final protein product.[2]:In other cases, the RNA molecules are the actual functional products, as in the synthesis of ribosomal RNA and transfer RNA. Some RNAs known as ribozymes are capable of enzymatic function, and microRNA has a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA genes.[41] Some viruses store their entire genomes in the form of RNA, and contain no DNA at all.[45][46] Because they use RNA to store genes, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription.[47] On the other hand, RNA retroviruses, such as HIV, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized. RNA-mediated epigenetic inheritance has also been observed in plants and very rarely in animals.[48] Inheritance[edit] Inheritance of a gene that has two different alleles (blue and white). The gene is located on an autosomal chromosome. The blue allele isrecessive to the white allele. The probability of each outcome in the children's generation is one quarter, or percent. Main articles: Mendelian inheritance and Heredity Organisms inherit their genes from their parents. Asexual organisms simply inherit a complete copy of their parent's genome. Sexual organisms have two copies of each chromosome because they inherit one complete set from each parent.[2]:Mendelian inheritance[edit] According to Mendelian inheritance, variations in an organism's phenotype (observable physical and behavioral characteristics) are due in part to variations in its genotype (particular set of genes). Each gene specifies a particular trait with different sequence of a gene (alleles) giving rise to different phenotypes. Most eukaryotic organisms (such as the pea plants Mendel worked on) have two alleles for each trait, one inherited from each parent.[2]:Alleles at a locus may be dominant or recessive; dominant alleles give rise to their corresponding phenotypes when paired with any other allele for the same trait, whereas recessive alleles give rise to their corresponding phenotype only when paired with another copy of the same allele. For example, if the allele specifying tall stems in pea plants is dominant over the allele specifying short stems, then pea plants that inherit one tall allele from one parent and one short allele from the other parent will also have tall stems. Mendel's work demonstrated that alleles assort independently in the production of gametes, or germ cells, ensuring variation in the next generation. Although Mendelian inheritance remains a good model for many traits determined by single genes (including a number of well-known genetic disorders) it does not include the physical processes of DNA replication and cell division.[49][50] DNA replication and cell division[edit] The growth, development, and reproduction of organisms relies on cell division, or the process by which a single cell divides into two usually identical daughter cells. This requires first making a duplicate copy of every gene in the genome in a process called DNA  in a process called DNA replication.[2]:The copies are made by specializedenzymes known as DNA polymerases, which "read" one strand of the double-helical DNA, known as the template strand, and synthesize a new complementary strand. Because the DNA double helix is held together by base pairing, the sequence of one strand completely specifies the sequence of its complement; hence only one strand needs to be read by the enzyme to produce a faithful copy. The process of DNA replication is semiconservative; that is, the copy of the genome inherited by each daughter cell contains one original and one newly synthesized strand of DNA.[2]:After DNA replication is complete, the cell must physically separate the two copies of the genome and divide into two distinct membrane-bound cells.[2]:In prokaryotes (bacteria and archaea) this usually occurs via a relatively simple process called binary fission, in which each circular genome attaches to the cell membrane and is separated into the daughter cells as the membrane invaginatesto split the cytoplasm into two membrane-bound portions. Binary fission is extremely fast compared to the rates of cell division in eukaryotes. Eukaryotic cell division is a more complex process known as the cell cycle; DNA replication occurs during a phase of this cycle known as S phase, whereas the process of segregating chromosomes and splitting the cytoplasm occurs during M phase.[2]:Molecular inheritance[edit] The duplication and transmission of genetic material from one generation of cells to the next is the basis for molecular inheritance, and the link between the classical and molecular pictures of genes. Organisms inherit the characteristics of their parents because the cells of the offspring contain copies of the genes in their parents' cells. In asexually reproducing organisms, the offspring will be a genetic copy or clone of the parent organism. In sexually reproducing organisms, a specialized form of cell division called meiosis produces cells called gametes or germ cells that are haploid, or contain only one copy of each gene.[2]:The gametes produced by females are called eggs or ova, and those produced by males are called sperm. Two gametes fuse to form a diploid fertilized egg, a single cell that has two sets of genes, with one copy of each gene from the mother and one from the father.[2]:During the process of meiotic cell division, an event called genetic recombination genetic recombination or crossing-over can sometimes occur, in which a length of DNA on one chromatid is swapped with a length of DNA on the corresponding sister chromatid. This has no effect if the alleles on the chromatids are the same, but results in reassortment of otherwise linked alleles if they are different.[2]:The Mendelian principle of independent assortment asserts that each of a parent's two genes for each trait will sort independently into gametes; which allele an organism inherits for one trait is unrelated to which allele it inherits for another trait. This is in fact only true for genes that do not reside on the same chromosome, or are located very far from one another on the same chromosome. The closer two genes lie on the same chromosome, the more closely they will be associated in gametes and the more often they will appear together; genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them. This is known as genetic linkage.[51] Molecular evolution[edit] Main article: Molecular evolution Mutation[edit] DNA replication is for the most part extremely accurate, however errors (mutations) do occur.[2]:The error rate in eukaryotic cells can be as low as 10−per nucleotide per replication,[52][53] whereas for some RNA viruses it can be as high as 10−3.[54] This means that each generation, each human genome accumulates 1–new mutations.[54] Small mutations can be caused by DNA replication and the aftermath of DNA damage and include point mutations in which a single base is altered and frameshift mutations in which a single base is inserted or deleted. Either of these mutations can change the gene by missense (change a codon to encode a different amino acid) or nonsense (a premature stop codon).[55] Larger mutations can be caused by errors in recombination to cause chromosomal abnormalities including the duplication, deletion, rearrangement or inversion of large sections of a chromosome. Additionally, the DNA repair mechanisms that normally revert mutations can introduce errors when repairing the physical damage to the molecule is more important than restoring an exact copy, for example when repairing double-strand breaks.[2]:When multiple different alleles for a gene are present in a species's population it is called polymorphic. Most different alleles are functionally equivalent, however some alleles can give rise to differentphenotypic traits. A gene's most common allele is called the wild type, and rare alleles are called mutants. The genetic variation in relative frequencies of different alleles in a population is due to bothnatural selection and genetic drift.[56] The wild-type allele is not necessarily the ancestor of less common alleles, nor is it necessarily fitter. Most mutations within genes are neutral, having no effect on the organism's phenotype (silent mutations). Some mutations do not change the amino acid sequence because multiple codons encode the same amino acid (synonymous mutations). Other mutations can be neutral if they lead to amino acid sequence changes, but the protein still functions similarly with the new amino acid (e.g.conservative mutations). Many mutations, however, are deleterious or even lethal, and are removed from populations by natural selection. Genetic disorders are the result of deleterious mutations and can be due to spontaneous mutation in the affected individual, or can be inherited. Finally, a small fraction of mutations are beneficial, improving the organism's fitness and are extremely important for evolution, since their directional selection leads to adaptive evolution.[2]:Sequence homology[edit] A sequence alignment, produced by ClustalO, of mammalian histoneproteins Genes with a most recent common ancestor, and thus a shared evolutionary ancestry, are known as homologs.[57] These genes appear either from gene duplication within an organism's genome, where they are known as paralogous genes, or are the result of divergence of the genes after a speciation event, where they are known as orthologous genes,[2]:and often perform the same or similar functions in related organisms. It is often assumed that the functions of orthologous genes are more similar than those of paralogous genes, although the difference is minimal.[58][59] The relationship between genes can be measured by comparing the sequence alignment of their DNA.[2]:The degree of sequence similarity between homologous genes is called conserved sequence. Most changes to a gene's sequence do not affect its function and so genes accumulate mutations over time by neutral molecular evolution. Additionally, any selection on a gene will cause its sequence to diverge at a different rate. Genes under stabilizing selection are constrained and so change more slowly whereas genes under directional selection change sequence more rapidly.[60] The sequence differences between genes can be used for phylogenetic analyses to study how those genes have evolved and how the organisms they come from are related.[61][62] Origins of new genes[edit] Evolutionary fate of duplicate genes The most common source of new genes in eukaryotic lineages is gene duplication, which creates copy number variation of an existing gene in the genome.[63][64] The resulting genes (paralogs) may then diverge in sequence and in function. Sets of genes formed in this way comprise a gene family. Gene duplications and losses within a family are common and represent a major source of evolutionary biodiversity.[65] Sometimes, gene duplication may result in a nonfunctional copy of a gene, or a functional copy may be subject to mutations that result in loss of function; such nonfunctional genes are called pseudogenes.[2]:De novo or "orphan" genes, whose sequence shows no similarity to existing genes, are extremely rare. Estimates of the number of de novo genes in the human genome range from 18[66] to 60.[67] Such genes are typically shorter and simpler in structure than most eukaryotic genes, with few if any introns.[63] Two primary sources of orphan protein-coding genes are gene duplication followed by extremely rapid sequence change, such that the original relationship is undetectable by sequence comparisons, and formation through mutation of "cryptic" transcription start sites that introduce a new open reading frame in a region of the genome that did not previously code for a protein.[68][69] Horizontal gene transfer refers to the transfer of genetic material through a mechanism other than reproduction. This mechanism is a common source of new genes in prokaryotes, sometimes thought to contribute more to genetic variation than gene duplication.[70] It is a common means of spreading antibiotic resistance, virulence, and adaptive metabolic functions.[28][71] Although horizontal gene transfer is rare in eukaryotes, likely examples have been identified of protist and alga genomes containing genes of bacterial origin.[72][73] Genome[edit] The genome is the total genetic material of an organism and includes both the genes and non-coding sequences.[74] Number of genes[edit] Representative genome sizes for plants (green), vertebrates (blue), invertebrates (red), fungus (yellow),bacteria (purple), and viruses (grey). An inset on the right shows the smaller genomes expanded 100-fold.[75][76][77][78][79][80][81][82] The genome size, and the number of genes it encodes varies widely between organisms. The smallest genomes occur in viruses (which can have as few as protein-coding genes),[83] andviroids (which act as a single non-coding RNA gene).[84] Conversely, plants can have extremely large genomes,[85] with rice containing >46,protein-coding genes.[86] The total number of protein-coding genes (the Earth's proteome) is estimated to be million sequences.[87] Although the number of base-pairs of DNA in the human genome has been known since the 1960s, the estimated number of genes has changed over time as definitions of genes, and methods of detecting them have been refined. Initial theoretical predictions of the number of human genes were as high as 2,000,000.[88] Early experimental measures indicated there to be 50,000–100,transcribed genes (expressed sequence tags).[89] Subsequently, the sequencing in the Human Genome Project indicated that many of these transcripts were alternative variants of the same genes, and the total number of protein-coding genes was revised down to ~20,000[82]with genes encoded on the mitochondrial genome.[80] Of the human genome, only 1–2% consists of protein-coding genes,[90] with the remainder being 'noncoding' DNA such as introns, retrotransposons, and noncoding RNAs.[90][91]Every organism has all his genes in all cells of his body but it is not important that every gene must function in every cell . Essential genes[edit] Main article: Essential gene Gene functions in the minimal genome of thesynthetic organism, Syn 3.[92] Essential genes are the set of genes thought to be critical for an organism's survival.[93] This definition assumes the abundant availability of all relevant nutrients and the absence of environmental stress. Only a small portion of an organism's genes are essential. In bacteria, an estimated 250–genes are essential for Escherichia coli and Bacillus subtilis, which is less than 10% of their genes.[94][95][96] Half of these genes are orthologs in both organisms and are largely involved in protein synthesis.[96] In the budding yeast Saccharomyces cerevisiae the number of essential genes is slightly higher, at genes (~20% of their genes).[97] Although the number is more difficult to measure in higher eukaryotes, mice and humans are estimated to have around essential genes (~10% of their genes).[98] The synthetic organism, Syn 3, has a minimal genome of essential genes and quasi-essential genes (necessary for fast growth), although have unknown function.[92] Essential genes include Housekeeping genes (critical for basic cell functions)[99] as well as genes that are expressed at different times in the organisms development or life cycle.[100] Housekeeping genes are used as experimental controls when analysing gene expression, since they areconstitutively expressed at a relatively constant level. Genetic and genomic nomenclature[edit] Gene nomenclature has been established by the HUGO Gene Nomenclature Committee (HGNC) for each known human gene in the form of an approved gene name and symbol (short-formabbreviation), which can be accessed through a database maintained by HGNC. Symbols are chosen to be unique, and each gene has only one symbol (although approved symbols sometimes change). Symbols are preferably kept consistent with other members of a gene family and with homologs in other species, particularly the mouse due to its role as a common model organism.[101] Genetic engineering[edit] Comparison of conventional plant breeding with transgenic and cisgenic genetic modification. Main article: Genetic engineering Genetic engineering is the modification of an organism's genome through biotechnology. Since the 1970s, a variety of techniques have been developed to specifically add, remove and edit genes in an organism.[102] Recently developed genome engineering techniques use engineerednuclease enzymes to create targeted DNA repair in a chromosome to either disrupt or edit a gene when the break is repaired.[103][104][105][106] The related term synthetic biology is sometimes used to refer to extensive genetic engineering of an organism.[107] Genetic engineering is now a routine research tool with model organisms. For example, genes are easily added to bacteria[108] and lineages ofknockout mice with a specific gene's function disrupted are used to investigate that gene's function.[109][110] Many organisms have been genetically modified for applications in agriculture, industrial biotechnology, and medicine. For multicellular organisms, typically the embryo is engineered which grows into the adult genetically modified organism