A chromosome and itspackaged long strand of DNA unraveled. The DNA'sbase pairs encode genes, which provide functions. A human DNA can have up to 500 million base pairs with thousands of genes.
Inbiology, the wordgene has two meanings. The Mendelian gene is a basic unit ofheredity. The molecular gene is a sequence ofnucleotides inDNA that is transcribed to produce a functionalRNA. There are two types of molecular genes: protein-coding genes and non-coding genes.[1][2][3] Duringgene expression (the synthesis ofRNA or protein from a gene), DNA is firstcopied into RNA. RNA can bedirectly functional or be the intermediatetemplate for the synthesis of a protein.
The transmission of genes to an organism'soffspring is the basis of the inheritance ofphenotypic traits from one generation to the next. These genes make up different DNA sequences, together called agenotype, that is specific to every given individual, within thegene pool of thepopulation of a givenspecies. The genotype, along with environmental and developmental factors, ultimately determines thephenotype of the individual.
There are many different ways to use the term "gene" based on different aspects of their inheritance, selection, biological function, or molecular structure but most of these definitions fall into two categories, the Mendelian gene or the molecular gene.[1][5][6][7][8]
The Mendelian gene is the classical gene of genetics and it refers to any heritable trait. This is the gene described inThe Selfish Gene.[9] More thorough discussions of this version of a gene can be found in the articlesGenetics andGene-centered view of evolution.
The molecular gene definition is more commonly used across biochemistry, molecular biology, and most of genetics—the gene that is described in terms of DNA sequence.[1] There are many different definitions of this gene—some of which are misleading or incorrect.[5][10]
Very early work in the field that becamemolecular genetics suggested the concept thatone gene makes one protein (originally 'one gene – one enzyme').[11][12] However, genes that produce repressor RNAs were proposed in the 1950s[13] and by the 1960s, textbooks were using molecular gene definitions that included those that specified functional RNA molecules such as ribosomal RNA and tRNA (noncoding genes) as well as protein-coding genes.[14]
This idea of two kinds of genes is still part of the definition of a gene in most textbooks. For example,
The primary function of the genome is to produce RNA molecules. Selected portions of the DNA nucleotide sequence are copied into a corresponding RNA nucleotide sequence, which either encodes a protein (if it is an mRNA) or forms a 'structural' RNA, such as a transfer RNA (tRNA) or ribosomal RNA (rRNA) molecule. Each region of the DNA helix that produces a functional RNA molecule constitutes a gene.[15]
We define a gene as a DNA sequence that is transcribed. This definition includes genes that do not encode proteins (not all transcripts are messenger RNA). The definition normally excludes regions of the genome that control transcription but are not themselves transcribed. We will encounter some exceptions to our definition of a gene - surprisingly, there is no definition that is entirely satisfactory.[16]
A gene is a DNA sequence that codes for a diffusible product. This product may be protein (as is the case in the majority of genes) or may be RNA (as is the case of genes that code for tRNA and rRNA). The crucial feature is that the product diffuses away from its site of synthesis to act elsewhere.[17]
The important parts of such definitions are: (1) that a gene corresponds to a transcription unit; (2) that genes produce both mRNA and noncoding RNAs; and (3) regulatory sequences control gene expression but are not part of the gene itself. However, there is one other important part of the definition and it is emphasized in Kostas Kampourakis' bookMaking Sense of Genes.
Therefore in this book I will consider genes as DNA sequences encoding information for functional products, be it proteins or RNA molecules. With 'encoding information', I mean that the DNA sequence is used as a template for the production of an RNA molecule or a protein that performs some function.[5]
The emphasis on function is essential because there are stretches of DNA that produce non-functional transcripts and they do not qualify as genes. These include obvious examples such as transcribed pseudogenes as well as less obvious examples such as junk RNA produced as noise due to transcription errors. In order to qualify as a true gene, by this definition, one has to prove that the transcript has a biological function.[5]
Early speculations on the size of a typical gene were based on high-resolution genetic mapping and on the size of proteins and RNA molecules. A length of 1500 base pairs seemed reasonable at the time (1965).[14] This was based on the idea that the gene was the DNA that was directly responsible for production of the functional product. The discovery of introns in the 1970s meant that many eukaryotic genes were much larger than the size of the functional product would imply. Typical mammalian protein-coding genes, for example, are about 62,000 base pairs in length (transcribed region) and since there are about 20,000 of them they occupy about 35–40% of the mammalian genome (including the human genome).[18][19][20]
In spite of the fact that both protein-coding genes and noncoding genes have been known for more than 50 years, there are still a number of textbooks, websites, and scientific publications that define a gene as a DNA sequence that specifies a protein. In other words, the definition is restricted to protein-coding genes. Here is an example from a 2021 article in American Scientist.
... to truly assess the potential significance of de novo genes, we relied on a strict definition of the word "gene" with which nearly every expert can agree. First, in order for a nucleotide sequence to be considered a true gene, an open reading frame (ORF) must be present. The ORF can be thought of as the "gene itself"; it begins with a starting mark common for every gene and ends with one of three possible finish line signals. One of the key enzymes in this process, the RNA polymerase, zips along the strand of DNA like a train on a monorail, transcribing it into its messenger RNA form. This point brings us to our second important criterion: A true gene is one that is both transcribed and translated. That is, a true gene is first used as a template to make transient messenger RNA, which is then translated into a protein.[21]
This restricted definition is so common that it has spawned many recent articles that criticize this "standard definition" and call for a new expanded definition that includes noncoding genes. However, some modern writers still do not acknowledge noncoding genes although this so-called "new" definition has been recognised for more than half a century.[22][23][24]
Although some definitions can be more broadly applicable than others, the fundamental complexity of biology means that no definition of a gene can capture all aspects perfectly. Not all genomes are DNA (e.g.RNA viruses),[25] bacterialoperons are multiple protein-coding regions transcribed into single large mRNAs,alternative splicing enables a single genomic region to encode multiple distinct products andtrans-splicing concatenates mRNAs from shorter coding sequence across the genome.[26][27][28] Since molecular definitions exclude elements such as introns, promotors, and otherregulatory regions, these are instead thought of as "associated" with the gene and affect its function.
An even broader operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products.[29] This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified asgene-associated regions.[29]
The existence of discrete inheritable units was first suggested byGregor Mendel (1822–1884).[30] From 1857 to 1864, inBrno,Austrian Empire (today's Czech Republic), he studied inheritance patterns in 8000 common ediblepea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the termgene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefiguredWilhelm Johannsen's distinction betweengenotype (the genetic material of an organism) andphenotype (the observable traits of that organism). Mendel was also the first to demonstrateindependent assortment, the distinction betweendominant andrecessive traits, the distinction between aheterozygote andhomozygote, and the phenomenon of discontinuous inheritance.
Prior to Mendel's work, the dominant theory of heredity was one ofblending inheritance,[31] which suggested that each parent contributed fluids to the fertilization process and that the traits of the parents blended and mixed to produce the offspring.Charles Darwin developed a theory of inheritance he termedpangenesis, fromGreek pan ("all, whole") and genesis ("birth") / genos ("origin").[32][33] Darwin used the termgemmule to describe hypothetical particles that would mix during reproduction.
Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century byHugo de Vries,Carl Correns, andErich von Tschermak, who (claimed to have) reached similar conclusions in their own research.[34] Specifically, in 1889, Hugo de Vries published his bookIntracellular Pangenesis,[35] in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" (Pangens in German), after Darwin's 1868 pangenesis theory.
Twenty years later, in 1909,Wilhelm Johannsen introduced the term "gene" (inspired by theancient Greek: γόνος,gonos, meaning offspring and procreation)[36] and, in 1906,William Bateson, that of "genetics"[37][29] whileEduard Strasburger, among others, still used the term "pangene" for the fundamental physical and functional unit of heredity.[35]: Translator's preface, viii
In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities arranged like beads on a string. The experiments ofBenzer usingmutants defective in therII region of bacteriophage T4 (1955–1959) showed that individual genes have a simple linear structure and are likely to be equivalent to a linear section of DNA.[42][43]
This view of evolution was emphasized byGeorge C. Williams'gene-centric view of evolution. He proposed that the Mendelian gene is aunit ofnatural selection with the definition: "that which segregates and recombines with appreciable frequency."[49]: 24 Related ideas emphasizing the centrality of Mendelian genes and the importance of natural selection in evolution were popularized byRichard Dawkins.[9][50]
The development of theneutral theory of evolution in the late 1960s led to the recognition that random genetic drift is a major player in evolution and that neutral theory should be the null hypothesis of molecular evolution.[51] This led to the construction ofphylogenetic trees and the development of themolecular clock, which is the basis of all dating techniques using DNA sequences. These techniques are not confined to molecular gene sequences but can be used on all DNA segments in the genome.
Two chains of DNA twist around each other to form a DNAdouble helix with the phosphate–sugar backbone spiralling around the outside, and the bases pointing inward with adeninebase pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form twohydrogen bonds, whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must, therefore, becomplementary, 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.[52]: 4.1
Due to the chemical composition of thepentose residues of the bases, DNA strands have directionality. One end of a DNApolymer contains an exposedhydroxyl group on thedeoxyribose; this is known as the3' end of the molecule. The other end contains an exposedphosphate group; this is the5' end. The two strands of a double-helix run in opposite directions. Nucleic acid synthesis, includingDNA replication andtranscription occurs in the 5'→3' direction, because new nucleotides are added via adehydration reaction that uses the exposed 3' hydroxyl as anucleophile.[53]: 27.2
Theexpression of genes encoded in DNA begins bytranscribing the gene intoRNA, a second type of nucleic acid that is very similar to DNA, but whose monomers contain the sugarribose rather thandeoxyribose. RNA also contains the baseuracil in place ofthymine. 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 calledcodons, which serve as the "words" in the genetic "language". Thegenetic code specifies the correspondence duringprotein translation between codons andamino acids. The genetic code is nearly the same for all known organisms.[52]: 4.1
The total complement of genes in an organism or cell is known as itsgenome, which may be stored on one or morechromosomes. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded.[52]: 4.2 The region of the chromosome at which a particular gene is located is called itslocus. Each locus contains oneallele of a gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence.
The majority ofeukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within thenucleus in complex with storage proteins calledhistones to form a unit called anucleosome. DNA packaged and condensed in this way is calledchromatin.[52]: 4.2 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 forgene 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 thecentromere.[52]: 4.2 Replication origins are the sequence regions whereDNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequences that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions duringDNA replication. The length of the telomeres decreases each time the genome is replicated and has been implicated in theaging process.[55] The centromere is required for bindingspindle fibres to separate sister chromatids into daughter cells duringcell division.[52]: 18.2
Prokaryotes (bacteria andarchaea) typically store their genomes on a single, large,circular chromosome. Similarly, some eukaryoticorganelles contain a remnant circular chromosome with a small number of genes.[52]: 14.4 Prokaryotes sometimes supplement their chromosome with additional small circles of DNA calledplasmids, which usually encode only a few genes and are transferable between individuals. For example, the genes forantibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, viahorizontal gene transfer.[56]
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 complexmulticellular organisms, including humans, contain an absolute majority of DNA without an identified function.[57] 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 thehuman genome, about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer.[26]
Thestructure of a protein-coding gene consists of many elements of which the actualprotein coding sequence is often only a small part. These include introns and untranslated regions of the mature mRNA. Noncoding genes can also contain introns that are removed during processing to produce the mature functional RNA.
All genes are associated withregulatory sequences that are required for their expression. First, genes require apromoter sequence. The promoter is recognized and bound bytranscription factors that recruit and helpRNA polymerase bind to the region to initiate transcription.[52]: 7.1 The recognition typically occurs as aconsensus sequence like theTATA box. A gene can have more than one promoter, resulting in messenger RNAs (mRNA) that differ in how far they extend in the 5' end.[59] Highly transcribed genes have "strong" promoter sequences that form strong associations with transcription factors, thereby initiating transcription at a high rate. Others genes have "weak" promoters that form weak associations with transcription factors and initiate transcription less frequently.[52]: 7.2 Eukaryoticpromoter regions are much more complex and difficult to identify thanprokaryotic promoters.[52]: 7.3
Additionally, genes can have regulatory regions many kilobases upstream or downstream of the gene that alter expression. These act bybinding to transcription factors which then cause the DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site.[60] For example,enhancers increase transcription by binding anactivator protein which then helps to recruit the RNA polymerase to the promoter; converselysilencers bindrepressor proteins and make the DNA less available for RNA polymerase.[61]
The mature messenger RNA produced from protein-coding genes containsuntranslated regions at both ends which contain binding sites forribosomes,RNA-binding proteins,miRNA, as well asterminator, andstart andstop codons.[62] In addition, most eukaryoticopen reading frames contain untranslatedintrons, which are removed andexons, which are connected together in a process known asRNA splicing. Finally, the ends of gene transcripts are defined bycleavage and polyadenylation (CPA) sites, where newly produced pre-mRNA gets cleaved and a string of ~200 adenosine monophosphates is added at the 3' end. Thepoly(A) tail protects mature mRNA from degradation and has other functions, affecting translation, localization, and transport of the transcript from the nucleus. Splicing, followed by CPA, generate the finalmature mRNA, which encodes the protein or RNA product.[63]
Many noncoding genes in eukaryotes have different transcription termination mechanisms and they do not have poly(A) tails.
Many prokaryotic genes are organized intooperons, with multiple protein-coding sequences that are transcribed as a unit.[64][65] The genes in anoperon are transcribed as a continuousmessenger RNA, referred to as apolycistronic mRNA. The termcistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by arepressor that can occur in an active or inactive state depending on the presence of specific metabolites.[66] When active, the repressor binds to a DNA sequence at the beginning of the operon, called theoperator region, and repressestranscription of theoperon; when the repressor is inactive transcription of the operon can occur (see e.g.Lac operon). The products of operon genes typically have related functions and are involved in the sameregulatory network.[52]: 7.3
Though many genes have simple structures, as with much of biology, others can be quite complex or represent unusual edge-cases. Eukaryotic genes often have introns that are much larger than their exons,[67][68] and those introns can even have other genesnested inside them.[69] Associated enhancers may be many kilobase away, or even on entirely different chromosomes operating via physical contact between two chromosomes.[70][71] A single gene can encode multiple different functional products byalternative splicing, and conversely a gene may be split across chromosomes but those transcripts are concatenated back together into a functional sequence bytrans-splicing.[72] It is also possible foroverlapping genes to share some of their DNA sequence, either on opposite strands or the same strand (in a different reading frame, or even the same reading frame).[73]
In all organisms, two steps are required to read the information encoded in a gene's DNA and produce the protein it specifies. First, the gene's DNA istranscribed to messenger RNA (mRNA).[52]: 6.1 Second, that mRNA istranslated to protein.[52]: 6.2 RNA-coding genes must still go through the first step, but are not translated into protein.[74] The process of producing a biologically functional molecule of either RNA or protein is calledgene expression, and the resulting molecule is called agene product.
Schematic of a single-stranded RNA molecule illustrating a series of three-basecodons. Each three-nucleotide codon corresponds to anamino acid when translated to protein.
The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through thegenetic code. Sets of three nucleotides, known ascodons, each correspond to a specific amino acid.[52]: 6 The principle that three sequential bases of DNA code for each amino acid was demonstrated in 1961 using frameshift mutations in the rIIB gene of bacteriophage T4[75] (seeCrick, Brenner et al. experiment).
Additionally, a "start codon", and three "stop codons" indicate the beginning and end of theprotein coding region. 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.[76]
Transcription produces a single-strandedRNA molecule known asmessenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed.[52]: 6.1 The mRNA acts as an intermediate between the DNA gene and its final protein product. The gene's DNA is used as a template to generate acomplementary mRNA. The mRNA matches the sequence of the gene's DNAcoding strand because it is synthesised as the complement of thetemplate strand. Transcription is performed by anenzyme called anRNA polymerase, which reads the template strand in the3' to5' direction and synthesizes the RNA from5' to3'. To initiate transcription, the polymerase first recognizes and binds apromoter region of the gene. Thus, a major mechanism ofgene regulation is the blocking or sequestering the promoter region, either by tight binding byrepressor molecules that physically block the polymerase or by organizing the DNA so that the promoter region is not accessible.[52]: 7
Inprokaryotes, transcription occurs in thecytoplasm; for very long transcripts, translation may begin at the 5' end of the RNA while the 3' end is still being transcribed. Ineukaryotes, transcription occurs in the nucleus, where the cell's DNA is stored. The RNA molecule produced by the polymerase is known as theprimary transcript and undergoespost-transcriptional modifications before being exported to the cytoplasm for translation. One of the modifications performed is thesplicing ofintrons which are sequences in the transcribed region that do not encode a protein.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 and also occurs in some prokaryotes.[52]: 7.5 [77]
Protein coding genes are transcribed to anmRNA intermediate, then translated to a functionalprotein. RNA-coding genes are transcribed to a functionalnon-coding RNA (PDB:3BSE,1OBB,3TRA).
Translation is the process by which amature mRNA molecule is used as a template for synthesizing a newprotein.[52]: 6.2 Translation is carried out byribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add newamino acids to a growingpolypeptide chain by the formation ofpeptide bonds. The genetic code is read three nucleotides at a time, in units calledcodons, via interactions with specialized RNA molecules calledtransfer RNA (tRNA). Each tRNA has three unpaired bases known as theanticodon that are complementary to the codon it reads on the mRNA. The tRNA is alsocovalently attached to theamino 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 fromamino terminus tocarboxyl terminus. During and after synthesis, most new proteins mustfold to their activethree-dimensional structure before they can carry out their cellular functions.[52]: 3
A typical protein-coding gene is first copied intoRNA as an intermediate in the manufacture of the final protein product.[52]: 6.1 In other cases, the RNA molecules are the actual functional products, as in the synthesis ofribosomal RNA andtransfer RNA. Some RNAs known asribozymes are capable ofenzymatic function, while others such asmicroRNAs andriboswitches have regulatory roles. TheDNA sequences from which such RNAs are transcribed are known asnon-coding RNA genes.[74]
Someviruses store their entire genomes in the form ofRNA, and contain no DNA at all.[79][80] Because they use RNA to store genes, theircellularhosts may synthesize their proteins as soon as they areinfected and without the delay in waiting for transcription.[81] On the other hand, RNAretroviruses, such asHIV, require thereverse transcription of theirgenome from RNA into DNA before their proteins can be synthesized.
Inheritance of a gene that has two differentalleles (blue and white). The gene is located on anautosomal chromosome. The white allele isrecessive to the blue allele. The probability of each outcome in the children's generation is one quarter, or 25 percent.
Organisms inherit their genes from their parents.Asexual organisms simply inherit a complete copy of their parent's genome.Sexual organisms have two copies of each chromosome because they inherit one complete set from each parent.[52]: 1
According toMendelian inheritance, variations in an organism'sphenotype (observable physical and behavioral characteristics) are due in part to variations in itsgenotype (particular set of genes). Each gene specifies a particular trait with a different sequence of a gene (alleles) giving rise to different phenotypes. Most eukaryotic organisms (such as the pea plants Mendel worked on) have two alleles for each trait, one inherited from each parent.[52]: 20
Alleles at a locus may bedominant orrecessive; 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. If you know the genotypes of the organisms, you can determine which alleles are dominant and which are recessive. 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 ofgametes, orgerm 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-knowngenetic disorders) it does not include the physical processes of DNA replication and cell division.[82][83]
The growth, development, and reproduction of organisms relies oncell division; the process by which a singlecell divides into two usually identicaldaughter cells. This requires first making a duplicate copy of every gene in thegenome in a process calledDNA replication.[52]: 5.2 The copies are made by specializedenzymes known asDNA 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 bybase 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 issemiconservative; that is, the copy of the genome inherited by each daughter cell contains one original and one newly synthesized strand of DNA.[52]: 5.2
The rate of DNA replication in living cells was first measured as the rate of phage T4 DNA elongation in phage-infectedE. coli and found to be impressively rapid.[84] During the period of exponential DNA increase at 37 °C, the rate of elongation was 749 nucleotides per second.
After DNA replication, the cell must physically separate the two genome copies and divide into two distinct membrane-bound cells.[52]: 18.2 Inprokaryotes (bacteria andarchaea) this usually occurs via a relatively simple process calledbinary fission, in which each circular genome attaches to thecell membrane and is separated into the daughter cells as the membraneinvaginates to split thecytoplasm into two membrane-bound portions. Binary fission is extremely fast compared to the rates of cell division ineukaryotes. Eukaryotic cell division is a more complex process known as thecell cycle; DNA replication occurs during a phase of this cycle known asS phase, whereas the process of segregatingchromosomes and splitting thecytoplasm occurs duringM phase.[52]: 18.1
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. Inasexually reproducing organisms, the offspring will be a genetic copy orclone of the parent organism. Insexually reproducing organisms, a specialized form of cell division calledmeiosis produces cells calledgametes orgerm cells that arehaploid, or contain only one copy of each gene.[52]: 20.2 The gametes produced by females are calledeggs or ova, and those produced by males are calledsperm. Two gametes fuse to form adiploidfertilized egg, a single cell that has two sets of genes, with one copy of each gene from the mother and one from the father.[52]: 20
During the process of meiotic cell division, an event calledgenetic recombination orcrossing-over can sometimes occur, in which a length of DNA on onechromatid is swapped with a length of DNA on the corresponding homologous non-sister chromatid. This can result in reassortment of otherwise linked alleles.[52]: 5.5 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 (known asgenetic linkage).[85] Genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them.[85]
Thegenome is the total genetic material of an organism and includes both the genes andnon-coding sequences.[86] Eukaryotic genes can be annotated using FINDER.[87]
Thegenome size, and the number of genes it encodes varies widely between organisms. The smallest genomes occur inviruses,[96] andviroids (which act as a single non-coding RNA gene).[97] Conversely, plants can have extremely large genomes,[98] withrice containing >46,000 protein-coding genes.[92] The total number of protein-coding genes (the Earth'sproteome) is estimated to be 5 million sequences.[99]
Although the number of base-pairs of DNA in the human genome has been known since the 1950s, the estimated number of genes has changed over time as definitions of genes, and methods of detecting them have been refined. Initial theoretical predictions of the number of human genes in the 1960s and 1970s were based on mutation load estimates and the numbers of mRNAs and these estimates tended to be about 30,000 protein-coding genes.[100][101][102] During the 1990s there were guesstimates of up to 100,000 genes and early data on detection of mRNAs (expressed sequence tags) suggested more than the traditional value of 30,000 genes that had been reported in the textbooks during the 1980s.[103]
The initial draft sequences of the human genome confirmed the earlier predictions of about 30,000 protein-coding genes however that estimate has fallen to about 19,000 with the ongoingGENCODE annotation project.[104] The number of noncoding genes is not known with certainty but the latest estimates from Ensembl suggest 26,000 noncoding genes.[105]
Essential genes are the set of genes thought to be critical for an organism's survival.[107] This definition assumes the abundant availability of all relevantnutrients and the absence of environmental stress. Only a small portion of an organism's genes are essential. In bacteria, an estimated 250–400 genes are essential forEscherichia coli andBacillus subtilis, which is less than 10% of their genes.[108][109][110] Half of these genes areorthologs in both organisms and are largely involved inprotein synthesis.[110] In the budding yeastSaccharomyces cerevisiae the number of essential genes is slightly higher, at 1000 genes (~20% of their genes).[111] Although the number is more difficult to measure in higher eukaryotes, mice and humans are estimated to have around 2000 essential genes (~10% of their genes).[112] The synthetic organism,Syn 3, has a minimal genome of 473 essential genes and quasi-essential genes (necessary for fast growth), although 149 have unknown function.[106]
Gene nomenclature was established by theHUGO Gene Nomenclature Committee (HGNC), a committee of theHuman Genome Organisation, for each known human gene in the form of an approved gene name andsymbol (short-formabbreviation), which can be accessed through a database maintained by HGNC. Symbols are chosen to be unique, and each gene has only one symbol (although approved symbols sometimes change). Symbols are preferably kept consistent with other members of agene family and with homologs in other species, particularly themouse due to its role as a commonmodel organism.[115]
Genetic engineering is now a routine research tool withmodel organisms. For example, genes are easily added tobacteria[122] and lineages ofknockout mice with a specific gene's function disrupted are used to investigate that gene's function.[123][124] Many organisms have been genetically modified for applications inagriculture, industrial biotechnology, andmedicine.
For multicellular organisms, typically theembryo is engineered which grows into the adultgenetically modified organism.[125] However, the genomes of cells in an adult organism can be edited usinggene therapy techniques to treat genetic diseases.
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^Johannsen W (1909).Elemente der exakten Erblichkeitslehre [Elements of the exact theory of heredity] (in German). Jena, Germany: Gustav Fischer. p. 124.Archived from the original on 24 June 2021. Retrieved16 June 2021. From p. 124:"Dieses "etwas" in den Gameten bezw. in der Zygote, ... – kurz, was wir eben Gene nennen wollen – bedingt sind." (This "something" in the gametes or in the zygote, which has crucial importance for the character of the organism, is usually called by the quite ambiguous termAnlagen [primordium, from the German wordAnlage for "plan, arrangement; rough sketch"]. Many other terms have been suggested, mostly unfortunately in closer connection with certain hypothetical opinions. The word "pangene", which was introduced by Darwin, is perhaps used most frequently in place ofAnlagen. However, the word "pangene" was not well chosen, as it is a compound word containing the rootspan (the neuter form of Πας all, every) andgen (from γί-γ(ε)ν-ομαι, to become). Only the meaning of this latter [i.e.,gen] comes into consideration here; just the basic idea – [namely,] that a trait in the developing organism can be determined or is influenced by "something" in the gametes – should find expression. No hypothesis about the nature of this "something" should be postulated or supported by it. For that reason it seems simplest to use in isolation the last syllablegen from Darwin's well-known word, which alone is of interest to us, in order to replace, with it, the poor, ambiguous wordAnlage. Thus we will say simply "gene" and "genes" for "pangene" and "pangenes". The word gene is completely free of any hypothesis; it expresses only the established fact that in any case many traits of the organism are determined by specific, separable, and thus independent "conditions", "foundations", "plans" – in short, precisely what we want to call genes.)
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