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Gene

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For a non-technical introduction to the topic, see Introduction to genetics. For other uses, see Gene (disambiguation).
DNA and gene diagram
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. The diagram labels a region of only 55 or so bases as a gene. In reality, most genes are hundreds of times longer.

A gene is the molecular unit of heredity of a living organism. The word is used extensively by the scientific community for stretches of deoxyribonucleic acids (DNA) and ribonucleic acids (RNA) that code for a polypeptide or for an RNA chain that has a function in the organism.[1][a] Living beings depend on genes, as they specify all proteins and functional RNA chains. Genes hold the information to build and maintain an organism's cells and pass genetic traits to offspring. All organisms have genes corresponding to various biological traits, some of which are instantly visible, such as eye color or number of limbs, and some of which are not, such as blood type, increased risk for specific diseases, or the thousands of basic biochemical processes that comprise life. The word gene was coined by Wilhelm Johannsen in 1909 and is indirectly derived (via pangene) from the Ancient Greek word γένος (génos) meaning "race, offspring".[2]

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 ".[3][4] Colloquial usage of the term gene (e.g., "good genes", "hair color gene") may actually refer to an allele: a gene is the basic instruction— a sequence of nucleic acids (DNA or, in the case of certain viruses RNA), while an allele is one variant of that gene. Thus, when the mainstream press refers to "having a gene" for a specific trait, this is customarily inaccurate. In most cases, all people would have a gene for the trait in question, although certain people will have a specific allele of that gene, which results in the trait variant. Further, genes code for proteins, which might result in identifiable traits, but it is the gene (genotype), not the trait (phenotype), which is inherited.

History[edit]

Photograph of Gregor Mendel
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). From 1857 to 1864, he studied inheritance patterns in 8000 common edible pea plants (Pisum), 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, which used the term gemmule to describe hypothetical particles that would mix during reproduction.

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 claimed to have reached similar conclusions in their own research. Danish botanist Wilhelm Johannsen coined the word "gene" ("gen" in Danish and German) in 1909 to describe the fundamental physical and functional units of heredity,[5] while the related word genetics was first used by William Bateson in 1905.[6]

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.[7][8] The structure of DNA was studied by Rosalind Franklin using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication.[9][10] 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 in retroviruses. 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 MS2 coat protein.[11] The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool.[12] An automated version of the Sanger method was used in early phases of the Human Genome Project.[13]

Modern synthesis[edit]

The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the modern evolutionary synthesis. The term was first used by Julian Huxley in his seminal work on the subject, Evolution: The Modern Synthesis. Evolutionary biologists have subsequently refined this concept, as in George C. Williams' gene-centric view of evolution presented in his 1966 book Adaptation and Natural Selection. He proposed an evolutionary concept of the gene as a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency." 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 in Richard Dawkins' books The Selfish Gene (1976) and The Extended Phenotype (1982).

Molecular basis[edit]

DNA[edit]

DNA chemical structure diagram showing how the double helix consists of two chains of sugar-phosphate backbone with bases pointing inwards and specifically base pairing A to T and C to G with hydrogen bonds.
The chemical structure of a four base pair fragment of a DNA 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.

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 four bases adenine, cytosine, guanine, and thymine.[1][b]

Two chains of DNA twist around each other to form 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 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.[1][c]

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 two strands of a double-helix run in opposite directions. Nucleic acid synthesis, including 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.

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.[1][d]

Chromosomes[edit]

fluorescent microscopy image of 46 pairs of chromosomes striped with red and yellow bands. The largest chromosomes are around 10 times the size of the smallest.
A karyotype of a human female, showing 46 paired chromosomes with regions rich in housekeeping genes stained in green.[14]

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.[1][e].

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 called chromatin.[1][f] The manner in which DNA is stored on the histones, as well as chemical 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.[1][g] 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.[15] The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division.

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. 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, via horizontal gene transfer.

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.[16] 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.[4]

RNA genes[edit]

A protein-coding gene in DNA being transcribed and translated to a functional protein or a non-protein-coding gene being transcribed to a functional RNA
Protein coding genes are transcribed to an mRNA intermediate, then translated to a functional protein. RNA-coding genes are transcribed to a functional non-coding RNA. (PDB 3BSE, 1OBB, 3TRA)

A typical protein-coding gene is first copied into RNA as an intermediate in the manufacture of the final protein product.[1][h] 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 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. RNA-mediated epigenetic inheritance has also been observed in plants and very rarely in animals.[17]

Gene expression[edit]

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.[1][i][j] 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[edit]

Main article: Genetic code
Codon position diagram
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 information encoded within a gene is translated into a functional protein. Each gene consists of a specific sequence of nucleotides encoded in DNA or RNA. The nucleotide being made up of a sugar, a phosphate molecule and a specific base (adenine, thymine, cytosine, guanine or sometimes uracil; thymine is replaced with uracil in some viruses[18]); 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, just as a specific set of 3 bases, "AUG", known as the "start codon", signifies the gene to start transcribing. 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[edit]

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 via the spliceosomal pathway 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[edit]

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 attaches 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.

Regulation[edit]

As gene expression draws on limited resources, it is desirable for genes to be expressed only when the product is needed. A number of different mechanisms have evolved to accomplish this. François Jacob, Jacques Monod and colleagues in 1961 published the first complete description of such a mechanism, the lac operon of E. coli.

Functional structure of a gene[edit]

The structure of a eukaryotic protein-coding gene. Regulatory sequence controls when and where expression occurs for the protein coding region (red). Promoter and enhancer regions (yellow) regulate the transcription of the gene into a pre-mRNA which is modified to add a 5' cap and poly-A tail (grey) and remove introns. The mRNA 5' and 3' untranslated regions (blue) regulate translation into the final protein product.
The structure of a prokaryotic operon of protein-coding genes. Regulatory sequence controls when expression occurs for the multiple protein coding regions (red). Promoter, operator and enhancer regions (yellow) regulate the transcription of the gene into an mRNA. The mRNA untranslated regions (blue) regulate translation into the final protein products.

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.[19] 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.[20]

Functional definitions[edit]

Early work in molecular genetics suggested that one gene makes one protein; this hypothesis was disproved by the discovery of alternative splicing and trans-splicing, through which many different proteins can be produced from a single gene,[6] and by the existence of RNA genes that have no protein product.

The definition of a gene at the molecular level continues to be refined. For example, 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. 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.[21] Even the coding sequence of a gene itself doesn't have to be all on the same chromosome: in the mitochondria of the protist Diplonema papillatum, "genes are systematically fragmented into small pieces that are encoded on separate chromosomes, transcribed individually, and then concatenated into contiguous messenger RNA molecules".[22]

The assumption that genes are discrete and 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 phenomenon is more frequent than previously thought.[23] Furthermore, some proteins can be composed of exons from far away regions and even different chromosomes.[4][24] Such phenomena have inspired a revised operational definition of a gene as "a union of genomic sequences encoding a coherent set of potentially overlapping functional products".[6] 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.[6]

Inheritance[edit]

Illustration of autosomal recessive inheritance. Each parent has one blue allele and one white allele. Each of their 4 children inherit one allele from each parent such that one child ends up with two blue alleles, one child has two white alleles and two children have one of each allele. Only the child with both blue alleles shows the trait because the trait is recessive.
Inheritance of a gene that has two different alleles (blue and white). The gene is located on an autosomal chromosome. The blue allele is recessive to the white allele. The probability of each outcome in the children's generation is one quarter, or 25 percent.

Mendelian inheritance and classical genetics[edit]

According to the theory of Mendelian inheritance, variations in phenotype—the observable physical and behavioral characteristics of an organism—are due in part 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 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 take into account the physical processes of DNA replication and cell division.

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 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.[25]

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[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. 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.

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.

Molecular evolution[edit]

Mutation[edit]

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.[25] (In prokaryotes and viruses, the rate is much higher.) 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. Common types of mutations include point mutations in which a single base is altered; frame shift mutations in which a single base is inserted or deleted; and nonsense mutations in which a stop codon is introduced, terminating transcription at this point.

Due to the degeneracy of the genetic code, some mutations in protein-coding genes are synonymous, or produce no change in the amino acid sequence of the protein for which they code. For example, the codons UCU and UCC both code for serine, so the U→C mutation has no effect on the sequence of the protein. Mutations that have no phenotypic effects – such as the large majority of synonymous mutations – are called silent mutations.

Mutations that do have phenotypic effects are most often neutral or deleterious to the organism. However, such variants may occasionally 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. Variation in the relative frequencies of different alleles can be attributed to both natural selection and genetic drift.

Sequence homology[edit]

The relationship between genes can be evaluated by examining their DNA sequences. This first requires that the sequences be aligned. Genes that have shared evolutionary ancestry are known as homologs, which can be divided into two categories: orthologs are genes whose ancestry involves a speciation event, while paralogs are genes whose ancestry involves a gene duplication event. Often, orthologous genes perform the same or similar functions in related organisms, so comparison of their sequences in different organisms can be used to calculate models for how the organisms are related. The degree of sequence similarity among homologous genes is called sequence conservation. It is often assumed that the functions of orthologous genes are more similar than those of paralogous genes, although this view has been disputed[26] and recent evidence suggests the effect is significant but weak.[27]

Genome[edit]

Chromosomal organization[edit]

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[edit]

Human genome pie chart
The protein-encoding component of the human genome, categorized by function of each gene product, given both as number of genes and as percentage of all genes.[28]

Early estimates of the number of human genes that used expressed sequence tag data put it at 50,000–100,000.[29] 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[30]) encode all the proteins in an organism.[31] These protein-coding sequences make up 1–2% of the human genome.[32] A large part of the genome is transcribed however, to introns, retrotransposons and seemingly a large array of noncoding RNAs.[31][32] Total number of proteins (the Earth's proteome) is estimated to be 5 million sequences.[33]

Essential genes[edit]

Main article: Essential genes

Essential genes are those genes that are thought to be critical for an organism's survival. This definition usually assumes the abundant availability of all relevant nutrients and the absence of environmental stress. Relatively few genes have been shown to be absolutely essential for the survival of bacteria. Many studies have attempted to characterize the essential gene complement of the common model bacterium Escherichia coli, producing estimates of around 10% of the approximately 4300 genes in the bacterium's genome.[34][35] As of a 2014 study, 295 protein-coding genes in E. coli and 253 in the bacterium Bacillus subtilis were considered essential, with about half of these genes representing orthologs in both organisms. The plurality of each organism's essential genes, and a majority of shared orthologs, are involved in protein synthesis.[36] In Saccharomyces cerevisiae (budding yeast), 1110 genes (around 20% of the genome) have been determined to be essential.[37] Estimates for the number of essential human genes vary from around 2500[38] to around 3800.[39]

Housekeeping genes are constitutive genes (that is, they are always expressed, at roughly the same level) that are critical for carrying out basic cell functions. Housekeeping genes are often used as experimental controls in studies of gene expression and as benchmarks for estimating organisms' shared ancestry. They may also be used as proxies for essential genes.[40] However, essential genes need not be housekeeping genes; they may instead be developmentally regulated and expressed at certain times during the organism's life cycle.[41]

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-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. 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.

Genetic engineering[edit]

Main article: Genetic engineering

Genetic engineering consists of modifying an organism's genome through biotechnology. Genes can be added to or removed from an organism, or its existing complement of genes can be altered. Deliberate genetic modification of organisms has been possible since the 1970s and has applications in research, agriculture, industrial biotechnology, and medicine. Bacteria were the first organisms to be genetically modified, and adding genes to bacteria through introduction of plasmids is now a routine procedure in molecular biology research.

A variety of techniques have been developed for precise manipulation of specific genes in an organism's chromosomes, often applied to altering or disrupting genes in model organisms. Mice are particularly common model organisms; a mouse line in which a specific gene's function has been disrupted is called a knockout mouse.

The technique of gene targeting exploits homologous recombination in embryonic stem cells to manipulate mouse genes[42] and has proved to be a productive tool for studying the in vivo effects of a variety of types of genetic modifications.[43][44]

Genome editing or genome engineering techniques are recently developed tools that take advantage of engineered nuclease enzymes (sometimes called "molecular scissors") to create double-strand breaks in a chromosome at a specific targeted location. Endogenous non-homologous end-joining (NHEJ) and homology-directed repair (HDR) processes then repair the site. Nucleases used for this purpose include zinc finger nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), the CRISPR/Cas system, and engineered meganucleases.[45][46][47][48]

See also[edit]

Notes and references[edit]

  1. ^ a b c d e f g h i Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular Biology of the Cell (Fourth ed.). New York: Garland Science. ISBN 978-0-8153-3218-3. 
  2. ^ "gene". Oxford English Dictionary (3rd ed.). Oxford University Press. September 2005. 
  3. ^ Pearson H (May 2006). "Genetics: what is a gene?". Nature 441 (7092): 398–401. Bibcode:2006Natur.441..398P. doi:10.1038/441398a. PMID 16724031. 
  4. ^ a b c Pennisi E (June 2007). "Genomics. DNA study forces rethink of what it means to be a gene". Science 316 (5831): 1556–1557. doi:10.1126/science.316.5831.1556. PMID 17569836. 
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