Gene

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotypical traits. Usage of the term "having a gene" (e.g., "good genes," "hair colour gene") typically refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection / survival of the fittest and genetic drift of the alleles.

The concept of a gene continues to be refined as new phenomena are discovered.[1] For example, regulatory regions of a gene can be far removed from its coding regions, and coding regions can be split into several exons. Some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. Therefore, a broad, modern working definition of a gene is any discrete locus of heritable, genomic sequence which affect an organism's traits by being expressed as a functional product or by regulation of gene expression.[2][3]

The term gene was introduced by Danish botanist, plant physiologist and geneticist Wilhelm Johannsen in 1905.[4] It is inspired by the ancient Greek: γόνος, gonos, that means offspring and procreation.

The image above contains clickable links
A gene is a region of DNA that encodes function. A chromosome consists of a long strand of DNA containing many genes. A human chromosome can have up to 500 million base pairs of DNA with thousands of genes.

History

Gregor Mendel
Gregor Mendel

Discovery of discrete inherited units

The existence of discrete inheritable units was first suggested by Gregor Mendel (1822–1884).[5] From 1857 to 1864, in Brno (Czech Republic), he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured Wilhelm Johannsen's distinction between genotype (the genetic material of an organism) and phenotype (the visible traits of that organism). Mendel was also the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the phenomenon of discontinuous inheritance.

Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which suggested that each parent contributed fluids to the fertilisation process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan ("all, whole") and genesis ("birth") / genos ("origin").[6][7] Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction.

Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries, Carl Correns, and Erich von Tschermak, who (claimed to have) reached similar conclusions in their own research.[8] Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis,[9] 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.

Sixteen years later, in 1905, Wilhelm Johannsen introduced the term 'gene'[4] and William Bateson that of 'genetics'[10] while Eduard Strasburger, amongst others, still used the term 'pangene' for the fundamental physical and functional unit of heredity.[11]

Discovery of DNA

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.[12][13] The structure of DNA was studied by Rosalind Franklin and Maurice Wilkins 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.[14][15]

In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination and arranged like beads on a string. The experiments of Benzer using mutants defective in the rII 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.[16][17]

Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics.

In 1972, Walter Fiers and his team were the first to determine the sequence of a gene: that of Bacteriophage MS2 coat protein.[18] 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.[19] An automated version of the Sanger method was used in early phases of the Human Genome Project.[20]

Modern synthesis and its successors

The theories developed in the early 20th century to integrate Mendelian genetics with Darwinian evolution are called the modern synthesis, a term introduced by Julian Huxley.[21]

Evolutionary biologists have subsequently modified this concept, such as George C. Williams' gene-centric view of evolution. He proposed an evolutionary concept of the gene as a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency."[22]:24 In this view, the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit. Related ideas emphasizing the centrality of genes in evolution were popularized by Richard Dawkins.[23][24]

Molecular basis

DNA chemical structure 2
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.

DNA

The vast majority of 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.[25]:2.1

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 to form two hydrogen bonds, whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must therefore be complementary, with their sequence of bases matching such that the adenines of one strand are paired with the thymines of the other strand, and so on.[25]:4.1

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.[26]:27.2

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.[25]:4.1

Chromosomes

PLoSBiol3.5.Fig7ChromosomesAluFish
Fluorescent microscopy image of a human female karyotype, showing 23 pairs of chromosomes . The DNA is stained red, with regions rich in housekeeping genes further stained in green. The largest chromosomes are around 10 times the size of the smallest.[27]

The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded.[25]:4.2 The region of the chromosome at which a particular gene is located is called its locus. Each locus contains one allele of a gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence.

The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome. DNA packaged and condensed in this way is called chromatin.[25]: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 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.[25]:4.2 Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequence that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication. The length of the telomeres decreases each time the genome is replicated and has been implicated in the aging process.[28] The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division.[25]:18.2

Prokaryotes (bacteria and archaea) typically store their genomes on a single large, circular chromosome. Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes.[25]:14.4 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.[29]

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.[30] 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.[3]

Structure and function

Structure

The structure of a gene consists of many elements of which the actual protein coding sequence is often only a small part. These include DNA regions that are not transcribed as well as untranslated regions of the RNA.

Flanking the open reading frame, genes contain a regulatory sequence that is required for their expression. First, genes require a promoter sequence. The promoter is recognized and bound by transcription factors that recruit and help RNA polymerase bind to the region to initiate transcription.[25]:7.1 The recognition typically occurs as a consensus sequence like the TATA 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.[32] 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.[25]:7.2 Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters.[25]:7.3

Additionally, genes can have regulatory regions many kilobases upstream or downstream of the open reading frame that alter expression. These act by binding to transcription factors which then cause the DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site.[33] For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase.[34]

The transcribed pre-mRNA contains untranslated regions at both ends which contain a ribosome binding site, terminator and start and stop codons.[35] In addition, most eukaryotic open reading frames contain untranslated introns which are removed before the exons are translated. The sequences at the ends of the introns dictate the splice sites to generate the final mature mRNA which encodes the protein or RNA product.[36]

Many prokaryotic genes are organized into operons, with multiple protein-coding sequences that are transcribed as a unit.[37][38] The genes in an operon are transcribed as a continuous messenger RNA, referred to as a polycistronic mRNA. The term cistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by a repressor that can occur in an active or inactive state depending on the presence of specific metabolites.[39] When active, the repressor binds to a DNA sequence at the beginning of the operon, called the operator region, and represses transcription of the operon; 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 same regulatory network.[25]:7.3

Functional definitions

Defining exactly what section of a DNA sequence comprises a gene is difficult.[1] Regulatory regions of a gene such as enhancers do not necessarily have to be close to the coding sequence on the linear molecule because the intervening DNA can be looped out to bring the gene and its regulatory region into proximity. Similarly, a gene's introns can be much larger than its exons. Regulatory regions can even be on entirely different chromosomes and operate in trans to allow regulatory regions on one chromosome to come in contact with target genes on another chromosome.[40][41]

Early work in molecular genetics suggested the concept that one gene makes one protein. This concept (originally called the one gene-one enzyme hypothesis) emerged from an influential 1941 paper by George Beadle and Edward Tatum on experiments with mutants of the fungus Neurospora crassa.[42] Norman Horowitz, an early colleague on the Neurospora research, reminisced in 2004 that “these experiments founded the science of what Beadle and Tatum called biochemical genetics. In actuality they proved to be the opening gun in what became molecular genetics and all the developments that have followed from that.”[43] The one gene-one protein concept has been refined since the discovery of genes that can encode multiple proteins by alternative splicing and coding sequences split in short section across the genome whose mRNAs are concatenated by trans-splicing.[3][44][45]

A broad operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products.[10] This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions.[10]

Gene expression

In all organisms, two steps are required to read the information encoded in a gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA (mRNA).[25]:6.1 Second, that mRNA is translated to protein.[25]:6.2 RNA-coding genes must still go through the first step, but are not translated into protein.[46] The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule is called a gene product.

Genetic code

RNA-codons-aminoacids
Schematic of a single-stranded RNA molecule illustrating a series of three-base codons. Each three-nucleotide codon corresponds to an amino acid when translated to protein

The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code. Sets of three nucleotides, known as codons, each correspond to a specific amino acid.[25]: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[47] (see Crick, Brenner et al. experiment).

Additionally, a "start codon", and three "stop codons" indicate the beginning and end of the protein 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.[48]

Transcription

Transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed.[25]: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 a complementary mRNA. The mRNA matches the sequence of the gene's DNA coding strand because it is synthesised as the complement of the template strand. Transcription is performed by an enzyme called 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 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.[25]:7

In prokaryotes, transcription occurs in the cytoplasm; for very long transcripts, translation may begin at the 5' end of the RNA while the 3' end is still being transcribed. In eukaryotes, transcription occurs in the nucleus, where the cell's DNA is stored. The RNA molecule produced by the polymerase is known as the primary transcript and undergoes post-transcriptional modifications before being exported to the cytoplasm for translation. One of the modifications performed is the splicing of introns which are sequences in the transcribed region that do not encode protein. Alternative 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.[25]:7.5[49]

Translation

DNA to protein or ncRNA
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​)

Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein.[25]:6.2 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 on the mRNA. The tRNA is also covalently attached to the amino acid specified by the complementary codon. When the tRNA binds to its complementary codon in an mRNA strand, the ribosome attaches its amino acid cargo to the new polypeptide chain, which is synthesized from amino terminus to carboxyl terminus. During and after synthesis, most new proteins must fold to their active three-dimensional structure before they can carry out their cellular functions.[25]:3

Regulation

Genes are regulated so that they are expressed only when the product is needed, since expression draws on limited resources.[25]:7 A cell regulates its gene expression depending on its external environment (e.g. available nutrients, temperature and other stresses), its internal environment (e.g. cell division cycle, metabolism, infection status), and its specific role if in a multicellular organism. Gene expression can be regulated at any step: from transcriptional initiation, to RNA processing, to post-translational modification of the protein. The regulation of lactose metabolism genes in E. coli (lac operon) was the first such mechanism to be described in 1961.[50]

RNA genes

A typical protein-coding gene is first copied into RNA as an intermediate in the manufacture of the final protein product.[25]:6.1 In other cases, the RNA molecules are the actual functional products, as in the synthesis of ribosomal RNA and transfer RNA. Some RNAs known as ribozymes are capable of enzymatic function, and microRNA has a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA genes.[46]

Some viruses store their entire genomes in the form of RNA, and contain no DNA at all.[51][52] 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.[53] 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.[54]

Inheritance

Autosomal recessive - mini
Inheritance of a gene that has two different alleles (blue and white). The gene is located on an autosomal chromosome. The white allele is recessive 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.[25]:1

Mendelian inheritance

According to Mendelian inheritance, variations in an organism's phenotype (observable physical and behavioral characteristics) are due in part to variations in its genotype (particular set of genes). Each gene specifies a particular trait with different sequence of a gene (alleles) giving rise to different phenotypes. Most eukaryotic organisms (such as the pea plants Mendel worked on) have two alleles for each trait, one inherited from each parent.[25]:20

Alleles at a locus may be dominant or recessive; dominant alleles give rise to their corresponding phenotypes when paired with any other allele for the same trait, whereas recessive alleles give rise to their corresponding phenotype only when paired with another copy of the same allele. 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 of gametes, or germ cells, ensuring variation in the next generation. Although Mendelian inheritance remains a good model for many traits determined by single genes (including a number of well-known genetic disorders) it does not include the physical processes of DNA replication and cell division.[55][56]

DNA replication and cell division

The growth, development, and reproduction of organisms relies on cell division; 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.[25]:5.2 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]:5.2

The rate of DNA replication in living cells was first measured as the rate of phage T4 DNA elongation in phage-infected E. coli and found to be impressively rapid.[57] During the period of exponential DNA increase at 37 °C, the rate of elongation was 749 nucleotides per second.

After DNA replication is complete, the cell must physically separate the two copies of the genome and divide into two distinct membrane-bound cells.[25]:18.2 In prokaryotes (bacteria and archaea) this usually occurs via a relatively simple process called binary fission, in which each circular genome attaches to the cell membrane and is separated into the daughter cells as the membrane 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.[25]:18.1

Molecular inheritance

The duplication and transmission of genetic material from one generation of cells to the next is the basis for molecular inheritance, and the link between the classical and molecular pictures of genes. Organisms inherit the characteristics of their parents because the cells of the offspring contain copies of the genes in their parents' cells. In asexually reproducing organisms, the offspring will be a genetic copy or clone of the parent organism. In sexually reproducing organisms, a specialized form of cell division called meiosis produces cells called gametes or germ cells that are haploid, or contain only one copy of each gene.[25]:20.2 The gametes produced by females are called eggs or ova, and those produced by males are called sperm. Two gametes fuse to form a diploid fertilized egg, a single cell that has two sets of genes, with one copy of each gene from the mother and one from the father.[25]:20

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 homologous non-sister chromatid. This can result in reassortment of otherwise linked alleles.[25]: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 as genetic linkage).[58] Genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them.[58]

Molecular evolution

Mutation

DNA replication is for the most part extremely accurate, however errors (mutations) do occur.[25]:7.6 The error rate in eukaryotic cells can be as low as 10−8 per nucleotide per replication,[59][60] whereas for some RNA viruses it can be as high as 10−3.[61] This means that each generation, each human genome accumulates 1–2 new mutations.[61] Small mutations can be caused by DNA replication and the aftermath of DNA damage and include point mutations in which a single base is altered and frameshift mutations in which a single base is inserted or deleted. Either of these mutations can change the gene by missense (change a codon to encode a different amino acid) or nonsense (a premature stop codon).[62] Larger mutations can be caused by errors in recombination to cause chromosomal abnormalities including the duplication, deletion, rearrangement or inversion of large sections of a chromosome. Additionally, DNA repair mechanisms can introduce mutational errors when repairing physical damage to the molecule. The repair, even with mutation, is more important to survival than restoring an exact copy, for example when repairing double-strand breaks.[25]:5.4

When multiple different alleles for a gene are present in a species's population it is called polymorphic. Most different alleles are functionally equivalent, however some alleles can give rise to different phenotypic traits. A gene's most common allele is called the wild type, and rare alleles are called mutants. The genetic variation in relative frequencies of different alleles in a population is due to both natural selection and genetic drift.[63] The wild-type allele is not necessarily the ancestor of less common alleles, nor is it necessarily fitter.

Most mutations within genes are neutral, having no effect on the organism's phenotype (silent mutations). Some mutations do not change the amino acid sequence because multiple codons encode the same amino acid (synonymous mutations). Other mutations can be neutral if they lead to amino acid sequence changes, but the protein still functions similarly with the new amino acid (e.g. conservative mutations). Many mutations, however, are deleterious or even lethal, and are removed from populations by natural selection. Genetic disorders are the result of deleterious mutations and can be due to spontaneous mutation in the affected individual, or can be inherited. Finally, a small fraction of mutations are beneficial, improving the organism's fitness and are extremely important for evolution, since their directional selection leads to adaptive evolution.[25]:7.6

Sequence homology

Histone Alignment
A sequence alignment, produced by ClustalO, of mammalian histone proteins

Genes with a most recent common ancestor, and thus a shared evolutionary ancestry, are known as homologs.[64] These genes appear either from gene duplication within an organism's genome, where they are known as paralogous genes, or are the result of divergence of the genes after a speciation event, where they are known as orthologous genes,[25]:7.6 and often perform the same or similar functions in related organisms. It is often assumed that the functions of orthologous genes are more similar than those of paralogous genes, although the difference is minimal.[65][66]

The relationship between genes can be measured by comparing the sequence alignment of their DNA.[25]:7.6 The degree of sequence similarity between homologous genes is called conserved sequence. Most changes to a gene's sequence do not affect its function and so genes accumulate mutations over time by neutral molecular evolution. Additionally, any selection on a gene will cause its sequence to diverge at a different rate. Genes under stabilizing selection are constrained and so change more slowly whereas genes under directional selection change sequence more rapidly.[67] The sequence differences between genes can be used for phylogenetic analyses to study how those genes have evolved and how the organisms they come from are related.[68][69]

Origins of new genes

Evolution fate duplicate genes - vector
Evolutionary fate of duplicate genes.

The most common source of new genes in eukaryotic lineages is gene duplication, which creates copy number variation of an existing gene in the genome.[70][71] The resulting genes (paralogs) may then diverge in sequence and in function. Sets of genes formed in this way compose a gene family. Gene duplications and losses within a family are common and represent a major source of evolutionary biodiversity.[72] Sometimes, gene duplication may result in a nonfunctional copy of a gene, or a functional copy may be subject to mutations that result in loss of function; such nonfunctional genes are called pseudogenes.[25]:7.6

"Orphan" genes, whose sequence shows no similarity to existing genes, are less common than gene duplicates. Estimates of the number of genes with no homologs outside humans range from 18[73] to 60.[74] Two primary sources of orphan protein-coding genes are gene duplication followed by extremely rapid sequence change, such that the original relationship is undetectable by sequence comparisons, and de novo conversion of a previously non-coding sequence into a protein-coding gene.[75] De novo genes are typically shorter and simpler in structure than most eukaryotic genes, with few if any introns.[70] Over long evolutionary time periods, de novo gene birth may be responsible for a significant fraction of taxonomically-restricted gene families.[76]

Horizontal gene transfer refers to the transfer of genetic material through a mechanism other than reproduction. This mechanism is a common source of new genes in prokaryotes, sometimes thought to contribute more to genetic variation than gene duplication.[77] It is a common means of spreading antibiotic resistance, virulence, and adaptive metabolic functions.[29][78] Although horizontal gene transfer is rare in eukaryotes, likely examples have been identified of protist and alga genomes containing genes of bacterial origin.[79][80]

Genome

The genome is the total genetic material of an organism and includes both the genes and non-coding sequences.[81]

Number of genes

Gene numbers
Representative genome sizes for plants (green), vertebrates (blue), invertebrates (red), fungus (yellow), bacteria (purple), and viruses (grey). An inset on the right shows the smaller genomes expanded 100-fold area-wise.[82][83][84][85][86][87][88][89]

The genome size, and the number of genes it encodes varies widely between organisms. The smallest genomes occur in viruses,[90] and viroids (which act as a single non-coding RNA gene).[91] Conversely, plants can have extremely large genomes,[92] with rice containing >46,000 protein-coding genes.[93] The total number of protein-coding genes (the Earth's proteome) is estimated to be 5 million sequences.[94]

Although the number of base-pairs of DNA in the human genome has been known since the 1960s, the estimated number of genes has changed over time as definitions of genes, and methods of detecting them have been refined. Initial theoretical predictions of the number of human genes were as high as 2,000,000.[95] Early experimental measures indicated there to be 50,000–100,000 transcribed genes (expressed sequence tags).[96] Subsequently, the sequencing in the Human Genome Project indicated that many of these transcripts were alternative variants of the same genes, and the total number of protein-coding genes was revised down to ~20,000[89] with 13 genes encoded on the mitochondrial genome.[87] With the GENCODE annotation project, that estimate has continued to fall to 19,000.[97] Of the human genome, only 1–2% consists of protein-coding genes,[98] with the remainder being 'noncoding' DNA such as introns, retrotransposons, and noncoding RNAs.[98][99] Every multicellular organism has all its genes in each cell of its body but not every gene functions in every cell .

Essential genes

Syn3 genome
Gene functions in the minimal genome of the synthetic organism, Syn 3.[100]

Essential genes are the set of genes thought to be critical for an organism's survival.[101] This definition assumes the abundant availability of all relevant nutrients and the absence of environmental stress. Only a small portion of an organism's genes are essential. In bacteria, an estimated 250–400 genes are essential for Escherichia coli and Bacillus subtilis, which is less than 10% of their genes.[102][103][104] Half of these genes are orthologs in both organisms and are largely involved in protein synthesis.[104] In the budding yeast Saccharomyces cerevisiae the number of essential genes is slightly higher, at 1000 genes (~20% of their genes).[105] 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).[106] 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.[100]

Essential genes include Housekeeping genes (critical for basic cell functions)[107] as well as genes that are expressed at different times in the organisms development or life cycle.[108] Housekeeping genes are used as experimental controls when analysing gene expression, since they are constitutively expressed at a relatively constant level.

Genetic and genomic nomenclature

Gene nomenclature has been established by the HUGO Gene Nomenclature Committee (HGNC) for each known human gene in the form of an approved gene name and symbol (short-form abbreviation), which can be accessed through a database maintained by HGNC. Symbols are chosen to be unique, and each gene has only one symbol (although approved symbols sometimes change). Symbols are preferably kept consistent with other members of a gene family and with homologs in other species, particularly the mouse due to its role as a common model organism.[109]

Genetic engineering

Breeding transgenesis cisgenesis
Comparison of conventional plant breeding with transgenic and cisgenic genetic modification.

Genetic engineering is the modification of an organism's genome through biotechnology. Since the 1970s, a variety of techniques have been developed to specifically add, remove and edit genes in an organism.[110] Recently developed genome engineering techniques use engineered nuclease enzymes to create targeted DNA repair in a chromosome to either disrupt or edit a gene when the break is repaired.[111][112][113][114] The related term synthetic biology is sometimes used to refer to extensive genetic engineering of an organism.[115]

Genetic engineering is now a routine research tool with model organisms. For example, genes are easily added to bacteria[116] and lineages of knockout mice with a specific gene's function disrupted are used to investigate that gene's function.[117][118] Many organisms have been genetically modified for applications in agriculture, industrial biotechnology, and medicine.

For multicellular organisms, typically the embryo is engineered which grows into the adult genetically modified organism.[119] However, the genomes of cells in an adult organism can be edited using gene therapy techniques to treat genetic diseases.

See also

References

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Sources

Main textbook

Further reading

External links

Allele

An allele () is a variant form of a given gene. Sometimes, the presence of different alleles of the same gene can result in different observable phenotypic traits, such as different pigmentation. A notable example of this trait of color variation is Gregor Mendel's discovery that the white and purple flower colors in pea plants were the result of "pure line" traits which could be used as a control for future experiments. However, most genetic variations result in little or no observable variation.

Most multicellular organisms have two sets of chromosomes; that is, they are diploid. In this case the chromosomes can be paired: each pair is made up of two chromosomes of the same type, known as homologous chromosomes. If both alleles at a gene (or locus) on the homologous chromosomes are the same, they and the organism are homozygous with respect to that gene (or locus). If the alleles are different, they and the organism are heterozygous with respect to that gene.

Cystic fibrosis

Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.CF is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Those with a single working copy are carriers and otherwise mostly normal. CFTR is involved in production of sweat, digestive fluids, and mucus. When the CFTR is not functional, secretions which are usually thin instead become thick. The condition is diagnosed by a sweat test and genetic testing. Screening of infants at birth takes place in some areas of the world.There is no known cure for cystic fibrosis. Lung infections are treated with antibiotics which may be given intravenously, inhaled, or by mouth. Sometimes, the antibiotic azithromycin is used long term. Inhaled hypertonic saline and salbutamol may also be useful. Lung transplantation may be an option if lung function continues to worsen. Pancreatic enzyme replacement and fat-soluble vitamin supplementation are important, especially in the young. Airway clearance techniques such as chest physiotherapy have some short-term benefit, but long-term effects are unclear. The average life expectancy is between 42 and 50 years in the developed world. Lung problems are responsible for death in 80% of people with cystic fibrosis.CF is most common among people of Northern European ancestry and affects about one out of every 3,000 newborns. About one in 25 people is a carrier. It is least common in Africans and Asians. It was first recognized as a specific disease by Dorothy Andersen in 1938, with descriptions that fit the condition occurring at least as far back as 1595. The name "cystic fibrosis" refers to the characteristic fibrosis and cysts that form within the pancreas.

Demi Moore

Demi Gene Guynes (born November 11, 1962), professionally known as Demi Moore ( də-MEE), is an American actress, former songwriter, and model. Moore dropped out of high school at age 16 to pursue an acting career and appeared in the men's pornographic magazine Oui in 1981. After making her film debut later that year, she appeared on the soap opera General Hospital and subsequently gained recognition as a member of the Brat Pack with roles in Blame It on Rio (1984), St. Elmo's Fire (1985), and About Last Night... (1986).Her starring role in Ghost (1990), the highest-grossing film of that year, earned her a Golden Globe nomination and established her as a leading actress in Hollywood. She continued to find box-office success with the films A Few Good Men (1992), Indecent Proposal (1993), and Disclosure (1994). In 1996, Moore became the highest-paid actress in film history when she received a then-unprecedented US$12.5 million to star in Striptease, a moderate financial success but a major critical disappointment, earning her several Golden Raspberry Awards, including for the Worst Actress. Her next major role, G.I. Jane (1997), for which she famously shaved her head, was followed by a lengthy break and downturn in Moore's career. Her later film roles include Charlie's Angels: Full Throttle (2003), Bobby (2006), Mr. Brooks (2007), and Margin Call (2011).

Besides acting, her personal life has been the subject of significant media coverage, particularly her marriages to actors Bruce Willis and Ashton Kutcher.

Dominance (genetics)

Dominance in genetics is a relationship between alleles of one gene, in which the effect on phenotype of one allele masks the contribution of a second allele at the same locus. The first allele is dominant and the second allele is recessive. For genes on an autosome (any chromosome other than a sex chromosome), the alleles and their associated traits are autosomal dominant or autosomal recessive. Dominance is a key concept in Mendelian inheritance and classical genetics. Often the dominant allele codes for a functional protein whereas the recessive allele does not.

A classic example of dominance is the inheritance of seed shape in peas. Peas may be round, associated with allele R, or wrinkled, associated with allele r. In this case, three combinations of alleles (genotypes) are possible: RR, Rr, and rr. The RR individuals have round peas and the rr individuals have wrinkled peas. In Rr individuals the R allele masks the presence of the r allele, so these individuals also have round peas. Thus, allele R is dominant to allele r, and allele r is recessive to allele R. This use of upper case letters for dominant alleles and lower case ones for recessive alleles is a widely followed convention.

More generally, where a gene exists in two allelic versions (designated A and a), three combinations of alleles are possible: AA, Aa, and aa. If AA and aa individuals (homozygotes) show different forms of some trait (phenotypes), and Aa individuals (heterozygotes) show the same phenotype as AA individuals, then allele A is said to dominate, be dominant to or show dominance to allele a, and a is said to be recessive to A.

Dominance is not inherent to either an allele or its phenotype. It is a relationship between two alleles of a gene and their associated phenotypes; one allele can be dominant over a second allele, recessive to a third allele, and codominant to a fourth. Also, an allele may be dominant for a particular aspect of phenotype but not for other aspects influenced by the same gene. Dominance differs from epistasis, a relationship in which an allele of one gene affects the expression of another allele at a different gene.

Gene Hackman

Eugene Allen Hackman (born January 30, 1930) is a retired American actor and novelist. In a career that spanned nearly five decades, Hackman was nominated for five Academy Awards, winning Best Actor in The French Connection and Best Supporting Actor in Unforgiven. He won four Golden Globes, one SAG Award and two BAFTAs.

He first came to fame in 1967 with his performance as Buck Barrow in Bonnie and Clyde, when he received his first Academy Award nomination for Best Supporting Actor. His major subsequent films include: I Never Sang for My Father (1970), when he received his second Best Supporting Actor nomination; The French Connection (1971) and French Connection II (1975), when he played Jimmy "Popeye" Doyle; The Poseidon Adventure (1972); The Conversation (1974); Superman: The Movie (1978), when he played arch-villain Lex Luthor; Hoosiers (1986); and Mississippi Burning (1988), when he received his second Best Actor nomination.

His film roles during the 1990s featured: Unforgiven (1992); The Firm (1993); The Quick and the Dead; Crimson Tide (1995); Get Shorty (1995); The Birdcage (1996); and Enemy of the State (1998) Later roles included: Behind Enemy Lines (2001); and The Royal Tenenbaums (2001). Hackman's final film appearance to date was the romantic comedy film Welcome to Mooseport in 2004, co-starring comedian Ray Romano.

Gene Kelly

Eugene Curran Kelly (August 23, 1912 – February 2, 1996) was an American dancer, actor of film, stage, and television, singer, film director, producer, and choreographer. He was known for his energetic and athletic dancing style, his good looks, and the likable characters that he played on screen.

Best known today for his performances in films such as An American in Paris (1951), Anchors Aweigh (1945)— for which he was nominated for the Academy Award for Best Actor—and Singin' in the Rain (1952), he starred in musical films until they fell out of fashion in the late 1950s. He starred in, choreographed or directed some of the most well-regarded musicals of the 1940s and 1950s, debuting with Judy Garland in For Me and My Gal (1942), and followed by Du Barry Was a Lady (1943), Thousands Cheer (1943), The Pirate (1948), On the Town (1949), and It's Always Fair Weather (1955), among others. In his later career, he starred in two films outside the musical genre: Inherit the Wind (1960) and What a Way to Go! (1964). Throughout his career he also directed films (some of which he starred in), most notably the 1969 film Hello, Dolly!, which was nominated for the Academy Award for Best Picture.His many innovations transformed the Hollywood musical, and he is credited with almost single-handedly making the ballet form commercially acceptable to film audiences.Kelly received an Academy Honorary Award in 1952 for his career achievements, the same year An American in Paris won six Academy Awards, including Best Picture. He later received lifetime achievement awards in the Kennedy Center Honors (1982), and from the Screen Actors Guild and American Film Institute. In 1999, the American Film Institute also ranked him as the 15th greatest male screen legend of Classic Hollywood Cinema.

Gene Roddenberry

Eugene Wesley Roddenberry (August 19, 1921 – October 24, 1991) was an American television screenwriter, producer and creator of the original Star Trek television series. Born in El Paso, Texas, Roddenberry grew up in Los Angeles, where his father was a police officer. Roddenberry flew 89 combat missions in the Army Air Forces during World War II, and worked as a commercial pilot after the war. Later, he followed in his father's footsteps and joined the Los Angeles Police Department, where he also began to write scripts for television.

As a freelance writer, Roddenberry wrote scripts for Highway Patrol, Have Gun–Will Travel, and other series, before creating and producing his own television series The Lieutenant. In 1964, Roddenberry created Star Trek, which premiered in 1966 and ran for three seasons before being canceled. He then worked on other projects, including a string of failed television pilots. The syndication of Star Trek led to its growing popularity; this, in turn, resulted in the Star Trek feature films, on which Roddenberry continued to produce and consult. In 1987, the sequel series Star Trek: The Next Generation began airing on television in first-run syndication; Roddenberry was heavily involved in the initial development of the series, but took a less active role after the first season due to ill health. He continued to consult on the series until his death in 1991.

In 1985, he became the first TV writer with a star on the Hollywood Walk of Fame, and he was later inducted by both the Science Fiction Hall of Fame and the Academy of Television Arts & Sciences Hall of Fame. Years after his death, Roddenberry was one of the first humans to have his ashes carried into earth orbit. The popularity of the Star Trek universe and films has inspired films, books, comic books, video games, and fan films set in the Star Trek universe.

Gene Simmons

Gene Klein (born Chaim Witz (Hebrew: חיים ויץ‎, [xaˈim ˈvit͡s]; August 25, 1949), known professionally as Gene Simmons, is an Israeli-American musician, singer, songwriter, record producer, entrepreneur, actor, author, and television personality. Also known by his stage persona The Demon, he is the bassist and co-lead singer of Kiss, the rock band he co-founded with lead singer and rhythm guitarist Paul Stanley in the early 1970s.

Gene Wilder

Jerome Silberman (June 11, 1933 – August 29, 2016), known professionally as Gene Wilder, was an American actor, screenwriter, director, producer, singer-songwriter and author.

Wilder began his career on stage, and made his screen debut in an episode of the TV series The Play of the Week in 1961. Although his first film role was portraying a hostage in the 1967 motion picture Bonnie and Clyde, Wilder's first major role was as Leopold Bloom in the 1967 film The Producers for which he was nominated for an Academy Award for Best Supporting Actor. This was the first in a series of collaborations with writer/director Mel Brooks, including 1974's Blazing Saddles and Young Frankenstein, which Wilder co-wrote, garnering the pair an Academy Award nomination for Best Adapted Screenplay. Wilder is known for his portrayal of Willy Wonka in Willy Wonka & the Chocolate Factory (1971) and for his four films with Richard Pryor: Silver Streak (1976), Stir Crazy (1980), See No Evil, Hear No Evil (1989), and Another You (1991). Wilder directed and wrote several of his own films, including The Woman in Red (1984).

With his third wife, Gilda Radner, he starred in three films, the last two of which he also directed. Her 1989 death from ovarian cancer led to his active involvement in promoting cancer awareness and treatment, helping found the Gilda Radner Ovarian Cancer Detection Center in Los Angeles and co-founding Gilda's Club.

After his last acting performance in 2003 – a guest role on Will & Grace for which he received an Emmy Award for Outstanding Guest Actor – Wilder turned his attention to writing. He produced a memoir in 2005, Kiss Me Like a Stranger: My Search for Love and Art; a collection of stories, What Is This Thing Called Love? (2010); and the novels My French Whore (2007), The Woman Who Wouldn't (2008) and Something to Remember You By (2013).

Gene expression

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as transfer RNA (tRNA) or small nuclear RNA (snRNA) genes, the product is a functional RNA.

The process of gene expression is used by all known life—eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses—to generate the macromolecular machinery for life.

Several steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-translational modification of a protein. Gene regulation gives the cell control over structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism. Gene regulation may also serve as a substrate for evolutionary change, since control of the timing, location, and amount of gene expression can have a profound effect on the functions (actions) of the gene in a cell or in a multicellular organism.

In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype, i.e. observable trait. The genetic code stored in DNA is "interpreted" by gene expression, and the properties of the expression give rise to the organism's phenotype. Such phenotypes are often expressed by the synthesis of proteins that control the organism's shape, or that act as enzymes catalysing specific metabolic pathways characterising the organism. Regulation of gene expression is thus critical to an organism's development.

Gene nomenclature

Gene nomenclature is the scientific naming of genes, the units of heredity in living organisms. An international committee published recommendations for genetic symbols and nomenclature in 1957. The need to develop formal guidelines for human gene names and symbols was recognized in the 1960s and full guidelines were issued in 1979 (Edinburgh Human Genome Meeting). Several other genus-specific research communities (e.g., Drosophila fruit flies, Mus mice) have adopted nomenclature standards, as well, and have published them on the relevant model organism websites and in scientific journals, including the Trends in Genetics Genetic Nomenclature Guide. Scientists familiar with a particular gene family may work together to revise the nomenclature for the entire set of genes when new information becomes available. For many genes and their corresponding proteins, an assortment of alternate names is in use across the scientific literature and public biological databases, posing a challenge to effective organization and exchange of biological information. Standardization of nomenclature thus tries to achieve the benefits of vocabulary control and bibliographic control, although adherence is voluntary. The advent of the information age has brought gene ontology, which in some ways is a next step of gene nomenclature, because it aims to unify the representation of gene and gene product attributes across all species.

Gene nomenclature and protein nomenclature are not separate endeavors; they are aspects of the same whole. Any name or symbol used for a protein can potentially also be used for the gene that encodes it, and vice versa. But owing to the nature of how science has developed (with knowledge being uncovered bit by bit over decades), proteins and their corresponding genes have not always been discovered simultaneously (and not always physiologically understood when discovered), which is the largest reason why protein and gene names do not always match, or why scientists tend to favor one symbol or name for the protein and another for the gene. Another reason is that many of the mechanisms of life are the same or very similar across species, genera, orders, and phyla (through homology, analogy, or some of both), so that a given protein may be produced in many kinds of organisms; and thus scientists naturally often use the same symbol and name for a given protein in one species (for example, mice) as in another species (for example, humans). Regarding the first duality (same symbol and name for gene or protein), the context usually makes the sense clear to scientific readers, and the nomenclatural systems also provide for some specificity by using italic for a symbol when the gene is meant and plain (roman) for when the protein is meant. Regarding the second duality (a given protein is endogenous in many kinds of organisms), the nomenclatural systems also provide for at least human-versus-nonhuman specificity by using different capitalization, although scientists often ignore this distinction, given that it is often biologically irrelevant.

Also owing to the nature of how scientific knowledge has unfolded, proteins and their corresponding genes often have several names and symbols that are synonymous. Some of the earlier ones may be deprecated in favor of newer ones, although such deprecation is voluntary. Some older names and symbols live on simply because they have been widely used in the scientific literature (including before the newer ones were coined) and are well established among users. For example, mentions of HER2 and ERBB2 are synonymous.

Lastly, the correlation between genes and proteins is not always one-to-one (in either direction); in some cases it is several-to-one or one-to-several, and the names and symbols may then be gene-specific or protein-specific to some degree, or overlapping in usage:

Some proteins and protein complexes are built from the products of several genes (each gene contributing a polypeptide subunit), which means that the protein or complex will not have the same name or symbol as any one gene. For example, a particular protein called "example" (symbol "EXAMP") may have 2 chains (subunits), which are encoded by 2 genes named "example alpha chain" and "example beta chain" (symbols EXAMPA and EXAMPB).

Some genes encode multiple proteins, because post-translational modification (PTM) and alternative splicing provide several paths for expression. For example, glucagon and similar polypeptides (such as GLP1 and GLP2) all come (via PTM) from proglucagon, which comes from preproglucagon, which is the polypeptide that the GCG gene encodes. When one speaks of the various polypeptide products, the names and symbols refer to different things (i.e., preproglucagon, proglucagon, glucagon, GLP1, GLP2), but when one speaks of the gene, all of those names and symbols are aliases for the same gene. Another example is that the various μ-opioid receptor proteins (e.g., μ1, μ2, μ3) are all splice variants encoded by one gene, OPRM1; this is how one can speak of MORs (μ-opioid receptors) in the plural (proteins) even though there is only one MOR gene, which may be called OPRM1, MOR1, or MOR—all of those aliases validly refer to it, although one of them (OPRM1) is preferred nomenclature.

Gene ontology

Gene ontology (GO) is a major bioinformatics initiative to unify the representation of gene and gene product attributes across all species. More specifically, the project aims to: 1) maintain and develop its controlled vocabulary of gene and gene product attributes; 2) annotate genes and gene products, and assimilate and disseminate annotation data; and 3) provide tools for easy access to all aspects of the data provided by the project, and to enable functional interpretation of experimental data using the GO, for example via enrichment analysis.

GO is part of a larger classification effort, the Open Biomedical Ontologies (OBO).Although gene nomenclature itself aims to maintain and develop controlled vocabulary of gene and gene products, the Gene Ontology extends the effort by using markup language to make the data (not only of the genes and their products but also of all their attributes) machine readable, and to do so in a way that is unified across all species (whereas gene nomenclature conventions vary by biologic taxon).

Gene therapy

In the medicine field gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patient's cells as a drug to treat disease. The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials were conducted, with more than half of them in phase I.

Not all medical procedures that introduce alterations to a patient's genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients. Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effect.

Genetic disorder

A genetic disorder is a genetic problem caused by one or more abnormalities formed in the genome. Most genetic disorders are quite rare and affect one person in every several thousands or millions.Genetic disorders may be hereditary, meaning that they are passed down from the parents' genes. In other genetic disorders, defects may be caused by new mutations or changes to the DNA. In such cases, the defect will only be passed down if it occurs in the germline.

Some types of recessive gene disorders confer an advantage in certain environments when only one copy of the gene is present.

Genetic engineering

Genetic engineering, also called genetic modification or genetic manipulation, is the direct manipulation of an organism's genes using biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus. As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or targeted to a specific part of the genome.

An organism that is generated through genetic engineering is considered to be genetically modified (GM) and the resulting entity is a genetically modified organism (GMO). The first GMO was a bacterium generated by Herbert Boyer and Stanley Cohen in 1973. Rudolf Jaenisch created the first GM animal when he inserted foreign DNA into a mouse in 1974. The first company to focus on genetic engineering, Genentech, was founded in 1976 and started the production of human proteins. Genetically engineered human insulin was produced in 1978 and insulin-producing bacteria were commercialised in 1982. Genetically modified food has been sold since 1994, with the release of the Flavr Savr tomato. The Flavr Savr was engineered to have a longer shelf life, but most current GM crops are modified to increase resistance to insects and herbicides. GloFish, the first GMO designed as a pet, was sold in the United States in December 2003. In 2016 salmon modified with a growth hormone were sold.

Genetic engineering has been applied in numerous fields including research, medicine, industrial biotechnology and agriculture. In research GMOs are used to study gene function and expression through loss of function, gain of function, tracking and expression experiments. By knocking out genes responsible for certain conditions it is possible to create animal model organisms of human diseases. As well as producing hormones, vaccines and other drugs genetic engineering has the potential to cure genetic diseases through gene therapy. The same techniques that are used to produce drugs can also have industrial applications such as producing enzymes for laundry detergent, cheeses and other products.

The rise of commercialised genetically modified crops has provided economic benefit to farmers in many different countries, but has also been the source of most of the controversy surrounding the technology. This has been present since its early use; the first field trials were destroyed by anti-GM activists. Although there is a scientific consensus that currently available food derived from GM crops poses no greater risk to human health than conventional food, GM food safety is a leading concern with critics. Gene flow, impact on non-target organisms, control of the food supply and intellectual property rights have also been raised as potential issues. These concerns have led to the development of a regulatory framework, which started in 1975. It has led to an international treaty, the Cartagena Protocol on Biosafety, that was adopted in 2000. Individual countries have developed their own regulatory systems regarding GMOs, with the most marked differences occurring between the US and Europe.

Genetics

Genetics is a branch of biology concerned with the study of genes, genetic variation, and heredity in organisms.Gregor Mendel, a scientist and Augustinian friar, discovered genetics in the late 19th-century. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring. He observed that organisms (pea plants) inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

Trait inheritance and molecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded beyond inheritance to studying the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of the cell, the organism (e.g. dominance), and within the context of a population. Genetics has given rise to a number of subfields, including epigenetics and population genetics. Organisms studied within the broad field span the domains of life (archaea, bacteria, and eukarya).

Genetic processes work in combination with an organism's environment and experiences to influence development and behavior, often referred to as nature versus nurture. The intracellular or extracellular environment of a cell or organism may switch gene transcription on or off. A classic example is two seeds of genetically identical corn, one placed in a temperate climate and one in an arid climate. While the average height of the two corn stalks may be genetically determined to be equal, the one in the arid climate only grows to half the height of the one in the temperate climate due to lack of water and nutrients in its environment.

Locus (genetics)

A locus (plural loci) in genetics is a fixed position on a chromosome, like the position of a gene or a marker (genetic marker). Each chromosome carries many genes; human's estimated 'haploid' protein coding genes are 19,000–20,000, on the 23 different chromosomes. A variant of the similar DNA sequence located at a given locus is called an allele. The ordered list of loci known for a particular genome is called a gene map. Gene mapping is the process of determining the locus for a particular biological trait.

Diploid and polyploid cells whose chromosomes have the same allele of a given gene at some locus are called homozygous with respect to that gene, while those that have different alleles of a given gene at a locus are called heterozygous with respect to that gene.

Mutation

In biology, a mutation is the permanent alteration of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA or other genetic elements.Mutations result from errors during DNA replication (especially during meiosis) or other types of damage to DNA (such as may be caused by exposure to radiation or carcinogens), which then may undergo error-prone repair (especially microhomology-mediated end joining), or cause an error during other forms of repair, or else may cause an error during replication (translesion synthesis). Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce discernible changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity.

The genomes of RNA viruses are based on RNA rather than DNA. The RNA viral genome can be double stranded (as in DNA) or single stranded. In some of these viruses (such as the single stranded human immunodeficiency virus) replication occurs quickly and there are no mechanisms to check the genome for accuracy. This error-prone process often results in mutations.

Mutation can result in many different types of change in sequences. Mutations in genes can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. Mutations can also occur in nongenic regions. One study on genetic variations between different species of Drosophila suggests that, if a mutation changes a protein produced by a gene, the result is likely to be harmful, with an estimated 70 percent of amino acid polymorphisms that have damaging effects, and the remainder being either neutral or marginally beneficial. Due to the damaging effects that mutations can have on genes, organisms have mechanisms such as DNA repair to prevent or correct mutations by reverting the mutated sequence back to its original state.

Nick Carter (musician)

Nickolas Gene Carter (born January 28, 1980) is an American musician and actor. He is best known as a member of the pop group the Backstreet Boys. As of 2015, Carter has released three solo albums, Now or Never, I'm Taking Off and All American during breaks between Backstreet Boys schedules, and a collaboration with Jordan Knight titled Nick & Knight. He has made occasional television appearances and starred in his own reality shows, House of Carters and I (Heart) Nick Carter. He gained fame in the mid 1990s and early 2000s as a teen idol. He is also the older brother of singer Aaron Carter and Leslie Carter.

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