Genes

=**Gene**=

A **gene** is the basic unit of __[|heredity]__ in a living __[|organism]__. All living things depend on genes. Genes hold the information to build and maintain their __[|cells]__ and pass genetic __[|traits]__ to offspring. A modern working definition of a gene is "//a__[|locatable region]__ of __[|genomic]__ sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions, and or other functional sequence regions// ".__[|[1]][|[2]]__ Incorrect colloquial usage of the term //gene// may actually refer to an __[|allele]__: a //gene// is the basic instruction, a sequence of DNA, while an//allele// is one variant of that instruction. The notion of a gene__[|[3]]__ is evolving with the science of __[|genetics]__, which began when __[|Gregor Mendel]__ noticed that biological variations are inherited from parent organisms as specific, discrete traits. The biological entity responsible for defining traits was termed a //gene//, but the biological basis for inheritance remained unknown until __[|DNA]__ was identified as the genetic material in the 1940s. All organisms have many genes corresponding to many different biological traits, some of which are immediately visible, such as __[|eye color]__ or number of limbs, and some of which are not, such as __[|blood type]__ or increased risk for specific diseases, or the thousands of basic __[|biochemical]__ processes that comprise __[|life]__. In __[|cells]__, a gene is a portion of __[|DNA]__ that contains both "coding" sequences that determine what the gene does, and "__[|non-coding]__" sequences that determine when the gene is active (__[|expressed]__). When a gene is active, the coding and non-coding sequences are copied in a process called __[|transcription]__, producing an __[|RNA]__ copy of the gene's information. This piece of RNA can then direct the synthesis of __[|proteins]__ via the __[|genetic code]__. In other cases, the RNA is used directly, for example as part of the __[|ribosome]__. The molecules resulting from gene expression, whether RNA or protein, are known as __[|gene products]__, and are responsible for the development and functioning of all living things. The physical __[|development]__ and __[|phenotype]__ of organisms can be thought of as a product of genes interacting with each other and with the environment.__[|[4]]__ A concise definition of a gene, taking into account complex patterns of regulation and transcription, genic conservation and non-coding RNA genes, has been proposed by Gerstein et al.:__[|[5]]__ "A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products".
 * [[image:http://upload.wikimedia.org/wikipedia/commons/thumb/0/07/Gene.png/270px-Gene.png height="216" link="http://en.wikipedia.org/wiki/File:Gene.png"]] This stylistic diagram shows a gene in relation to the double helix structure of __[|DNA]__ and to a__[|chromosome]__ (right). The chromosome is X-shaped because it is dividing. __[|Introns]__ are regions often found in __[|eukaryote]__ genes that are removed in the __[|splicing]__ process (after the DNA is transcribed into RNA): Only the __[|exons]__encode the __[|protein]__. This diagram labels a region of only 50 or so bases as a gene. In reality, most genes are hundreds of times larger. ||

** History **
//Main article: __[|History of genetics]__// The existence of genes was first suggested by __[|Gregor Mendel]__ (1822–1884), who, in the 1860s, studied inheritance in __[|peaplants]__ (//Pisum sativum//) and __[|hypothesized]__ a factor that conveys traits from parent to offspring. He spent over 10 years of his life on one experiment. 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]__ (the genetic material of an organism) and__[|phenotype]__ (the visible traits of that organism). Mendel's concept was given a name by __[|Hugo de Vries]__ in 1889, who, at that time probably unaware of Mendel's work, in his book //Intracellular Pangenesis// coined the term "pangen" for "the smallest particle [representing] one hereditary characteristic".__[|[6]] [|Wilhelm Johannsen]__ abbreviated this term to "gene" ("gen" in Danish and German) two decades later. 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 the fruit fly//__[|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 __[|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 specific steps in __[|metabolic pathways]__. This showed that specific genes code for specific proteins, leading to the "__[|one gene, one enzyme]__" hypothesis.__[|[7]] [|Oswald Avery]__, __[|Colin Munro MacLeod]__, and __[|Maclyn McCarty] [|showed in 1944]__ that DNA holds the gene's information.__[|[8]]__ 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 translated from __[|RNA]__ which is transcribed from DNA. This dogma has since been shown to have exceptions, such as __[|reverse transcription]__ in __[|retroviruses]__. In 1972, __[|Walter Fiers]__ and his team at the Laboratory of Molecular Biology of the __[|University of Ghent]__ (__[|Ghent]__, __[|Belgium]__) were the first to determine the sequence of a gene: the gene for __[|Bacteriophage MS2]__ coat protein.__[|[9]] [|Richard J. Roberts]__ and __[|Phillip Sharp]__ discovered in 1977 that genes can be split into segments. This leads to the idea that one gene can make several proteins. Recently (as of 2003–2006), __[|biological]__ results let the notion of gene appear more slippery. In particular, genes do not seem to sit side by side on __[|DNA]__ like discrete beads. Instead, __[|regions]__ of the DNA producing distinct proteins may overlap, so that the idea emerges that "genes are one long __[|continuum]__".__[|[1]]__

** Mendelian inheritance and classical genetics **
//Main articles: __[|Mendelian inheritance]__ and __[|Classical genetics]__// Darwin used the term __[|Gemmule]__ to describe a microscopic unit of inheritance, and what would later become known as __[|Chromosomes]__ had been observed separating out during cell division by __[|Wilhelm Hofmeister]__ as early as 1848. The idea that chromosomes are the carriers of inheritance was expressed in 1883 by __[|Wilhelm Roux]__. The modern conception of the gene originated with work by __[|Gregor Mendel]__, a 19th-century __[|Augustinian]__ monk who systematically studied heredity in pea plants. Mendel's work was the first to illustrate __[|particulate inheritance]__, or the theory that inherited traits are passed from one generation to the next in discrete units that interact in well-defined ways. __[|Danish] [|botanist] [|Wilhelm Johannsen]__ coined the word "gene" in 1909 to describe these fundamental physical and functional units of heredity,__[|[10]]__ while the related word __[|genetics]__ was first used by __[|William Bateson]__ in 1905.__[|[7]]__ The word was derived from __[|Hugo de Vries]__' 1889 term //pangen// for the same concept,__[|[6]]__ itself a derivative of the word //__[|pangenesis]__// coined by __[|Darwin]__ (1868).__[|[11]]__ The word pangenesis is made from the __[|Greek]__ words //pan// (a prefix meaning "whole", "encompassing") and //genesis// ("birth") or //genos// ("origin"). Crossing between two pea plants __[|heterozygous]__ for purple (B, dominant) and white (b, recessive) blossoms According to the theory of __[|Mendelian inheritance]__, variations in __[|phenotype]__—the observable physical and behavioral characteristics of an organism—are due to variations in __[|genotype]__, or the organism's particular set of genes, each of which specifies a particular trait. Different forms of a gene, which may give rise to different phenotypes, are known as __[|alleles]__. Organisms such as the pea plants Mendel worked on, along with many plants and animals, have two alleles for each trait, one inherited from each parent. Alleles 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 found that alleles assort independently in the production of __[|gametes]__, or __[|germ cells]__, ensuring variation in the next generation. Prior to Mendel's work, the dominant theory of heredity was one of __[|blending inheritance]__, which proposes that the traits of the parents blend or mix in a smooth, continuous gradient in the offspring. Although Mendel's work was largely unrecognized after its first publication in 1866, it was rediscovered in 1900 by three European scientists, __[|Hugo de Vries]__, __[|Carl Correns]__, and __[|Erich von Tschermak]__, who had reached similar conclusions from their own research. However, these scientists were not yet aware of the identity of the 'discrete units' on which genetic material resides. A series of subsequent discoveries led to the realization decades later that __[|chromosomes]__ within __[|cells]__ are the carriers of genetic material, and that they are made of __[|DNA]__(deoxyribonucleic acid), a __[|polymeric]__ molecule found in all cells on which the 'discrete units' of Mendelian inheritance are encoded. The modern study of __[|genetics]__ at the level of DNA is known as __[|molecular genetics]__ and the synthesis of molecular genetics with traditional __[|Darwinian] [|evolution]__ is known as the __[|modern evolutionary synthesis]__.

** Physical definitions **
The chemical structure of a four-base fragment of a__[|DNA]__ double helix. The vast majority of living organisms encode their genes in long strands of __[|DNA]__. DNA consists of a chain made from four types of __[|nucleotide]__ subunits: __[|adenine]__, __[|cytosine]__, __[|guanine]__, and __[|thymine]__. Each nucleotide subunit consists of three components: a __[|phosphate]__ group, a __[|deoxyribose]__ sugar ring, and a __[|nucleobase]__. Thus, nucleotides in DNA or RNA are typically called 'bases'; as a consequence, they are commonly referred to simply by their __[|purine]__ or__[|pyrimidine]__ original base components adenine, cytosine, guanine, thymine. Adenine and guanine are purines, and cytosine and thymine are pyrimidines. The most common form of DNA in a cell is in a __[|double helix]__ structure, in which two individual DNA strands twist around each other in a right-handed spiral. In this structure, the __[|base pairing]__ rules specify that __[|guanine]__ pairs with __[|cytosine]__ and __[|adenine]__ pairs with __[|thymine]__ (each pair contains one purine and one pyrimidine). The base pairing between guanine and cytosine forms three __[|hydrogen bonds]__, whereas the base pairing between adenine and thymine forms two hydrogen bonds. The two strands in a double helix must therefore be //complementary//, that is, their bases must align such that the adenines of one strand are paired with the thymines of the other strand, and so on. 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 exposed __[|phosphate]__ group; this is the __[|5' end]__. The directionality of DNA is vitally important to many cellular processes, since double helices are necessarily directional (a strand running 5'-3' pairs with a complementary strand running 3'-5'), and processes such as __[|DNA replication]__ occur in only one direction. All nucleic acid synthesis in a cell occurs in the 5'-3' direction, because new monomers are added via a__[|dehydration]__ reaction that uses the exposed 3' hydroxyl as a __[|nucleophile]__. 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 than __[|deoxyribose]__. 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 and __[|amino acids]__. The genetic code is nearly the same for all known organisms.

** RNA genes and genomes **
In some cases, __[|RNA]__ is an intermediate product in the process of manufacturing proteins from genes. However, for other gene sequences, the RNA molecules are the actual functional products. For example, RNAs known as __[|ribozymes]__ are capable of __[|enzymatic function]__, and __[|miRNAs]__ have a regulatory role. The __[|DNA]__ sequences from which such RNAs are transcribed are known as __[|RNA genes]__. Some __[|viruses]__ store their entire genomes in the form of RNA, and contain no DNA at all. 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. 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. In 2006, French researchers came across a puzzling example of RNA-mediated inheritance in mouse. Mice with a __[|loss-of-function mutation]__ in the gene Kit have white tails. Offspring of these mutants can have white tails despite having only normal Kit genes. The research team traced this effect back to mutated Kit RNA.__[|[12]]__ While RNA is common as genetic storage material in viruses, in mammals in particular RNA inheritance has been observed very rarely.

** Functional structure of a gene **
Diagram of the "typical" __[|eukaryotic]__ protein-coding **gene**. __[|Promoters]__and __[|enhancers]__ determine what portions of the __[|DNA]__ will be__[|transcribed]__ into the __[|precursor mRNA]__ (pre-mRNA). The pre-mRNA is then spliced into __[|messenger RNA]__ (mRNA) which is later __[|translated]__into __[|protein]__. All genes have regulatory regions in addition to regions that explicitly code for a protein or RNA product. A __[|regulatory region]__ shared by almost all genes is known as the __[|promoter]__, which provides a position that is recognized by the transcription machinery when a gene is about to be transcribed and expressed. A gene can have more than one promoter, resulting in RNAs that differ in how far they extend in the 5' end.__[|[13]]__ Although promoter regions have a __[|consensus sequence]__ that is the most common sequence at this position, some genes have "strong" promoters that bind the transcription machinery well, and others have "weak" promoters that bind poorly. These weak promoters usually permit a lower rate of transcription than the strong promoters, because the transcription machinery binds to them and initiates transcription less frequently. Other possible regulatory regions include __[|enhancers]__, which can compensate for a weak promoter. Most regulatory regions are "upstream"—that is, before or toward the 5' end of the transcription initiation site. __[|Eukaryotic] [|promoter]__ regions are much more complex and difficult to identify than __[|prokaryotic]__ promoters. Many prokaryotic genes are organized into __[|operons]__, or groups of genes whose products have related functions and which are transcribed as a unit. By contrast, __[|eukaryotic genes]__ are transcribed only one at a time, but may include long stretches of DNA called __[|introns]__ which are transcribed but never translated into protein (they are spliced out before translation). Splicing can also occur in prokaryotic genes, but is less common than in eukaryotes.__[|[14]]__

** Chromosomes **
The total complement of genes in an organism or cell is known as its __[|genome]__, which may be stored on one or more __[|chromosomes]__; the region of the chromosome at which a particular gene is located is called its __[|locus]__. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. __[|Prokaryotes]__ - __[|bacteria]__ and __[|archaea]__ - typically store their genomes on a single large, circular chromosome, sometimes supplemented by additional small circles of DNA called __[|plasmids]__, which usually encode only a few genes and are easily 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, via __[|horizontal gene transfer]__. Although some simple eukaryotes also possess plasmids with small numbers of genes, the majority of eukaryotic genes are stored on multiple linear chromosomes, which are packed within the __[|nucleus]__ in complex with storage proteins called __[|histones]__. The manner in which DNA is stored on the histone, as well as chemical modifications of the histone itself, are regulatory mechanisms governing whether a particular region of DNA is accessible for __[|gene expression]__. The ends of eukaryotic chromosomes are capped by long stretches of repetitive sequences called __[|telomeres]__, which do not code for any gene product but are present to prevent degradation of coding and regulatory regions during __[|DNA replication]__. The length of the telomeres tends to decrease each time the genome is replicated in preparation for cell division; the loss of telomeres has been proposed as an explanation for cellular __[|senescence]__, or the loss of the ability to divide, and by extension for the __[|aging]__ process in organisms.__[|[15]]__ Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain so-called "__[|junk DNA]__", or 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.__[|[16]]__ However it now appears that, although protein-coding DNA makes up barely 2% of the__[|human genome]__, about 80% of the bases in the genome may be being expressed, so the term "junk DNA" may be a misnomer.__[|[2]]__

** Gene expression **
//Main article: __[|Gene expression]__// In all organisms, there are two major steps separating a protein-coding gene from its protein: First, the DNA on which the gene resides must be //__[|transcribed]__// from DNA to __[|messenger RNA]__ (mRNA); and, second, it must be //__[|translated]__// from mRNA to protein. RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called __[|gene expression]__, and the resulting molecule itself is called a__[|gene product]__.

** Genetic code **
//Main article: __[|Genetic code]__// Schematic diagram of a single-stranded RNA molecule illustrating the position of three-base codons. The genetic code is the set of rules by which a gene is translated into a functional protein. Each gene consists of a specific sequence of nucleotides encoded in a DNA (or sometimes RNA) strand; a correspondence between nucleotides, the basic building blocks of genetic material, and amino acids, the basic building blocks of proteins, must be established for genes to be successfully translated into functional proteins. Sets of three nucleotides, known as __[|codons]__, each correspond to a specific amino acid or to a signal; three codons are known as "stop codons" and, instead of specifying a new amino acid, alert the translation machinery that the end of the gene has been reached. There are 64 possible codons (four possible nucleotides at each of three positions, hence 43 possible codons) and only 20 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 organisms.

** Transcription **
The process of genetic __[|transcription]__ produces a single-stranded __[|RNA]__ molecule known as __[|messenger RNA]__, whose nucleotide sequence is complementary to the DNA from which it was transcribed. The DNA strand whose sequence matches that of the RNA is known as the __[|coding strand]__ and the strand from which the RNA was synthesized is the __[|template strand]__. Transcription is performed by an __[|enzyme]__ called an __[|RNA 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 of 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. 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 necessarily occurs in the nucleus, where the cell's DNA is sequestered; the RNA molecule produced by the polymerase is known as the__[|primary transcript]__ and must undergo __[|post-transcriptional modifications]__ before being exported to the cytoplasm for translation. The __[|splicing]__ of __[|introns]__ present within the transcribed region is a modification unique to eukaryotes; __[|alternative splicing]__ mechanisms 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.

** Translation **
__[|Translation]__ is the process by which a __[|mature mRNA]__ molecule is used as a template for synthesizing a new __[|protein]__. Translation is carried out by __[|ribosomes]__, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new __[|amino acids]__ to a growing __[|polypeptide chain]__ by the formation of __[|peptide bonds]__. The genetic code is read three nucleotides at a time, in units called __[|codons]__, via interactions with specialized RNA molecules called __[|transfer RNA]__ (tRNA). Each tRNA has three unpaired bases known as the __[|anticodon]__ that are complementary to the codon it reads; 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 ligates its amino acid cargo to the new polypeptide chain, which is synthesized from __[|amino terminus]__ to __[|carboxyl terminus]__. During and after its synthesis, the new protein must __[|fold]__ to its active __[|three-dimensional structure]__before it can carry out its cellular function.

** DNA replication and inheritance **
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 replication]__. The copies are made by specialized __[|enzymes]__ 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.__[|[17]]__ After DNA replication is complete, the cell must physically separate the two copies of the genome and divide into two distinct membrane-bound cells. 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 __[|invaginates]__ to 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]__. In many single-celled eukaryotes such as__[|yeast]__, reproduction by __[|budding]__ is common, which results in asymmetrical portions of cytoplasm in the two daughter cells.

** Molecular inheritance **
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. The gametes produced by females are called__[|eggs]__ or ova, and those produced by males are called __[|sperm]__. Two gametes fuse to form a __[|fertilized egg]__, a single cell that once again has a __[|diploid]__ number of genes—each with one copy from the mother and one copy from the father. During the process of meiotic cell division, an event called __[|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. 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]__.

** Mutation **
//Main article: __[|Mutation]__// DNA replication is for the most part extremely accurate, with an error rate per site of around 10−6 to 10−10 in __[|eukaryotes]__.__[|[17]]__ Rare, spontaneous alterations in the base sequence of a particular gene arise from a number of sources, such as errors in __[|DNA replication]__ and the aftermath of __[|DNA damage]__. These errors are called __[|mutations]__. The cell contains many __[|DNA repair]__ mechanisms for preventing mutations and maintaining the integrity of the genome; however, in some cases—such as breaks in both DNA strands of a chromosome — repairing the physical damage to the molecule is a higher priority than producing an exact copy. Due to the degeneracy of the genetic code, some mutations in protein-coding genes are //silent//, or produce no change in the __[|amino acid sequence]__ of the protein for which they code; for example, the codons__[|UCU]__ and __[|UUC]__ both code for __[|serine]__, so the U↔C mutation has no effect on the protein. Mutations that do have phenotypic effects are most often neutral or deleterious to the organism, but sometimes they confer benefits to the organism's __[|fitness]__. Mutations propagated to the next __[|generation]__ 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. Although it is rare for the variants in a single gene to have clearly distinguishable phenotypic effects, certain well-defined traits are in fact controlled by single genetic loci. A gene's most common allele is called the __[|wild type]__ allele, and rare alleles are called __[|mutants]__. However, this does not imply that the wild-type allele is the __[|ancestor]__ from which the __[|mutants]__ are descended.

** Chromosomal organization **
The total complement of genes in an organism or cell is known as its __[|genome]__. In __[|prokaryotes]__, the vast majority of genes are located on a single chromosome of __[|circular DNA]__, while __[|eukaryotes]__ usually possess multiple individual linear DNA helices packed into dense DNA-protein complexes called __[|chromosomes]__. Genes that appear together on one chromosome of one species may appear on separate chromosomes in another species. Many species carry more than one copy of their genome within each of their __[|somatic cells]__. Cells or organisms with only one copy of each chromosome are called __[|haploid]__; those with two copies are called __[|diploid]__; and those with more than two copies are called __[|polyploid]__. The copies of genes on the chromosomes are not necessarily identical. In sexually reproducing organisms, one copy is normally inherited from each parent.

** Number of genes **
Early estimates of the number of human genes that used __[|expressed sequence tag]__ data put it at 50 000–100 000.__[|[18]]__ Following the __[|sequencing of the human genome]__ and other genomes, it has been found that rather few genes (~20 000 in human, mouse and fly, ~13 000 in roundworm, >46 000 in rice) encode all the __[|proteins]__ in an organism.__[|[19]]__ These protein-coding sequences make up 1–2% of the human genome.__[|[20]]__ Most of the genome gives rise to RNA products however, but not much is known about the function of these __[|non-coding RNAs]__.__[|[19]][|[20]]__

** Genetic and genomic nomenclature **
__[|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-form __[|abbreviation]__). All approved symbols are stored in the [|HGNC 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 be used in other __[|species]__, especially the __[|mouse]__.

** Evolutionary concept of a gene **
__[|George C. Williams]__ first explicitly advocated the __[|gene-centric view of evolution]__ in his 1966 book //__[|Adaptation and Natural Selection]__//. He proposed an evolutionary concept of gene to be used when we are talking about __[|natural selection]__ favoring some genes. The definition is: "that which segregates and recombines with appreciable frequency." According to this definition, even an __[|asexual]__ genome could be considered a gene, insofar that it have an appreciable permanency through many generations. The difference is: the molecular gene //transcribes// as a unit, and the evolutionary gene //inherits// as a unit. __[|Richard Dawkins]__' books //__[|The Selfish Gene]__// (1976) and //__[|The Extended Phenotype]__// (1982) defended the idea that the gene is the only __[|replicator]__ in living systems. This means that only genes transmit their structure largely intact and are potentially immortal in the form of copies. So, genes should be the __[|unit of selection]__. In //The Selfish Gene// Dawkins attempts to redefine the word 'gene' to mean "an inheritable unit" instead of the generally accepted definition of "a section of DNA coding for a particular protein". In //__[|River Out of Eden]__//, Dawkins further refined the idea of gene-centric selection by describing life as a river of compatible genes flowing through __[|geological time]__. Scoop up a bucket of genes from the river of genes, and we have an __[|organism]__ serving as temporary bodies or __[|survival machines]__. A river of genes may fork into two branches representing two non-__[|interbreeding] [|species]__ as a result of geographical separation.

** Gene targeting and implications **
//Main article: __[|Gene targeting]__// Gene targeting is commonly referred to techniques for altering or disrupting mouse genes and provides the mouse models for studying the roles of individual genes in__[|embryonic development]__, human disorders, aging and diseases. The mouse models, where one or more of its genes are deactivated or made inoperable, are called__[|knockout mice]__. Since the first reports in which __[|homologous recombination]__ in __[|embryonic stem cells]__ was used to generate gene-targeted mice,__[|[21]]__ gene targeting has proven to be a powerful means of precisely manipulating the mammalian genome, producing at least ten thousand mutant mouse strains and it is now possible to introduce mutations that can be activated at specific time points, or in specific cells or organs, both during development and in the adult animal.__[|[22]][|[23]]__ Gene targeting strategies have been expanded to all kinds of modifications, including __[|point mutations]__, isoform deletions, mutant allele correction, large pieces of chromosomal DNA __[|insertion]__ and __[|deletion]__, tissue specific disruption combined with spatial and temporal regulation and so on. It is predicted that the ability to generate mouse models with predictable phenotypes will have a major impact on studies of all phases of development, __[|immunology]__, __[|neurobiology]__, __[|oncology]__, __[|physiology]__,__[|metabolism]__, and human diseases. Gene targeting is also in theory applicable to species from which __[|totipotent]__ embryonic stem cells can be established, and therefore may offer a potential to the improvement of domestic animals and plants.__[|[23]][|[24]]__

** Changing concept **
The concept of the gene has changed considerably (see __[|history section]__). From the original definition of a "unit of inheritance", the term evolved to mean a __[|DNA]__-based unit that can exert its effects on the organism through __[|RNA]__ or __[|protein]__ products. It was also previously believed that one gene makes one protein; this concept was overthrown by the discovery of __[|alternative splicing]__ and __[|trans-splicing]__.__[|[7]]__ The definition of a gene is still changing. The first cases of RNA-based __[|inheritance]__ have been discovered in mammals.__[|[12]]__ Evidence is also accumulating that the __[|control regions]__ of a gene do not necessarily have to be close to the __[|coding sequence]__ on the linear molecule or even on the same chromosome. Spilianakis and colleagues discovered that the __[|promoter region]__ of the __[|interferon-gamma]__ gene on chromosome 10 and the regulatory regions of the T(H)2 __[|cytokine]__ locus on chromosome 11 come into close proximity in the __[|nucleus]__ possibly to be jointly regulated.__[|[25]]__ The concept that genes are clearly delimited is also being eroded. There is evidence for fused proteins stemming from two adjacent genes that can produce two separate protein products. While it is not clear whether these fusion proteins are functional, the phenomena is more frequent than previously thought.__[|[26]]__ Even more ground-breaking than the discovery of fused genes is the observation that some proteins can be composed of __[|exons]__ from far away regions and even different chromosomes.__[|[2]][|[27]]__ This new data has led to an updated, and probably tentative, definition of a gene as "a union of genomic sequences encoding a coherent set of potentially overlapping functional products."__[|[7]]__ This new definition categorizes genes by functional products, whether they be proteins or RNA, rather than specific DNA loci; all regulatory elements of DNA are therefore classified as //gene-associated// regions.__[|[7]]__ > Wikipedia® is a registered trademark of the __[|Wikimedia Foundation, Inc.]__, a non-profit organization.
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