- Plural of gene
- Plural of gene
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. The physical development and phenotype of organisms can be thought of as a product of genes interacting with each other and with the environment. 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. "A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products".
Colloquially, the term gene is often used to refer to an inheritable trait which is usually accompanied by a phenotype as in ("tall genes" or "bad genes") -- the proper scientific term for this is allele.
In cells, genes consist of a long strand of DNA that contains a promoter, which controls the activity of a gene, and coding and non-coding sequence. Coding sequence determines what the gene produces, while non-coding sequence can regulate the conditions of gene expression. When a gene is active, the coding and non-coding sequence is copied in a process called transcription, producing an RNA copy of the gene's information. This RNA can then direct the synthesis of proteins via the genetic code. But some RNAs are used directly, for example as part of the ribosome. These molecules resulting from gene expression, whether RNA or protein, are known as gene products.
Genes often contain regions that do not encode products, but regulate gene expression. The genes of eukaryotic organisms can contain regions called introns that are removed from the messenger RNA in a process called splicing. The regions encoding gene products are called exons. In eukaryotes, a single gene can encode multiple proteins, which are produced through the creation of different arrangements of exons through alternative splicing. In prokaryotes (bacteria and archaea), introns are less common and genes often contain a single uninterrupted stretch of DNA, called a cistron, that codes for a product. Prokaryotic genes are often arranged in groups called operons with promoter and operator sequences that regulate transcription of a single long RNA. This RNA contains multiple coding sequences. Each coding sequence is preceded by a Shine-Dalgarno sequence that ribosomes recognize.
The total set of genes in an organism is known as its genome. An organism's genome size is generally lower in prokaryotes, both in number of base pairs and number of genes, than even single-celled eukaryotes. However, there is no clear relationship between genome sizes and complexity in eukaryotic organisms. One of the largest known genomes belongs to the single-celled amoeba Amoeba dubia, with over 670 billion base pairs, some 200 times larger than the human genome. The estimated number of genes in the human genome has been repeatedly revised downward since the completion of the Human Genome Project; current estimates place the human genome at just under 3 billion base pairs and about 20,000–25,000 genes. A recent Science article gives a number of 20,488 protein-coding genes, with perhaps 100 more yet to be discovered. The gene density of a genome is a measure of the number of genes per million base pairs (called a megabase, Mb); prokaryotic genomes have much higher gene densities than eukaryotes. The gene density of the human genome is roughly 12–15 genes per megabase pair.
The existence of genes was first suggested by Gregor Mendel (1822-1884), who, in the 1860s, studied inheritance in pea plants 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 and phenotype. 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". 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". while the related word genetics was first used by William Bateson in 1905. itself a derivative of the word pangenesis coined by Darwin (1868). The word pangenesis is made from the Greek words pan (a prefix meaning "whole", "encompassing") and genesis ("birth") or genos ("origin").
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, while 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 definitionsThe 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'; consequently 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, while 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 genesIn 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. 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
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. 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.
ChromosomesThe 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.
While 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, while the genomes of complex multicellular organisms, including humans, contain an absolute majority of DNA without an identified function. Computational gene finding methods are still significantly more reliable than earlier techniques that required mapping the locations of specific mutations that gave rise to distinguishable alleles. Moreover, the genes are often fragmented internally by non-coding sequences called introns, which can be many times longer than the coding sequence but are spliced during post-transcriptional modification of pre-mRNA.
Genetic and genomic nomenclatureGene 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 geneGeorge 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' The Selfish Gene and The Extended Phenotype 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 implicationsGene 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, 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.
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.
The concept of the gene has changed considerably (see history section). Originally considered a "unit of inheritance" to a usually 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 has been overthrown by the discovery of alternative splicing and trans-splicing. In plants, cases of traits reappearing after several generations of absence have led researchers to hypothesise RNA-directed overwriting of genomic DNA. 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.
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. 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. 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.
Tutorial and news
- Science aid: Genetics for beginners
- Recount slashes number of human genes (from New Scientist magazine)
- National Human Genome Research Institute — News Release
References and databases
- Bioinformatic Harvester A Meta search engine (29 databases) for gene and protein information.
- HUGO Gene Nomenclature Committee, HGNC
- OMIM NIH's National Library of Medicine NCBI website link to Online Mendelian Inheritance in Man.
- Human Genome Organisation, HUGO
- iHOP - Information Hyperlinked over Proteins
- Entrez Gene - A searchable database of genes
- IDconverter - Map your ids to other known public DBs
- GeneCards - the Human Gene Compendium
- Gene Therapy Net
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