document_title: Gene

question_text: the location of a gene on a chromosome is called a(n)

question_tokens: the location of a gene on a chromosome is called a ( n )

text: Gene

text: History[edit]

text: Discovery of discrete inherited units[edit]

text: 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.

text: 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.

text: 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.

text: 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]

text: Discovery of DNA[edit]

text: 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]

text: 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]

text: 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.

text: In 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein.[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]

text: Modern synthesis and its successors[edit]

text: 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]

text: 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]

text: Molecular basis[edit]

text: DNA[edit]

text: The vast majority of living organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar (2'-deoxyribose), a phosphate group, and one of the four bases adenine, cytosine, guanine, and thymine.[25]:2.1

text: 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

text: 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

text: 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

text: Chromosomes[edit]

text: 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.

text: 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

text: 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]

text: 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]

text: Structure and function[edit]

text: Structure[edit]

text:
Regulatory sequence
Regulatory sequence
Enhancer
/silencer
Promoter
5'UTR
Open reading frame
3'UTR
Enhancer
/silencer
Proximal
Core
Start
Stop
Terminator
Transcription
DNA
Exon
Exon
Exon
Intron
Intron
Post-transcriptional
modification
Pre-
mRNA
Protein coding region
5'cap
Poly-A tail
Translation
Mature
mRNA
Protein

The structure of a eukaryotic protein-coding gene. Regulatory sequence controls when and where expression occurs for the protein coding region (red). Promoter and enhancer regions (yellow) regulate the transcription of the gene into a pre-mRNA which is modified to remove introns (light grey) and add a 5' cap and poly-A tail (dark grey). The mRNA 5' and 3' untranslated regions (blue) regulate translation into the final protein product.[31]

Polycistronic operon
Regulatory sequence
Regulatory sequence
Enhancer
Enhancer
/silencer
/silencer
Operator
Promoter
5'UTR
ORF
ORF
UTR
3'UTR
Start
Start
Stop
Stop
Terminator
Transcription
DNA
RBS
RBS
Protein coding region
Protein coding region
mRNA
Translation
Protein

The structure of a prokaryotic operon of protein-coding genes. Regulatory sequence controls when expression occurs for the multiple protein coding regions (red). Promoter, operator and enhancer regions (yellow) regulate the transcription of the gene into an mRNA. The mRNA untranslated regions (blue) regulate translation into the final protein products.[31]

text: 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.

text: 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 and RNA polymerase 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

text: 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]

text: 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]

text: 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 certain 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

text: Functional definitions[edit]

text: 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]

text: 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]

text: 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]

text: Gene expression[edit]

text: 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.

text: Genetic code[edit]

text: 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).

text: 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]

text: Transcription[edit]

text: 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

text: 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]

text: Translation[edit]

text: 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

text: Regulation[edit]

text: 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]

text: RNA genes[edit]

text: 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]

text: 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]

text: Inheritance[edit]

text: 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

text: Mendelian inheritance[edit]

text: 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

text: 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]

text: DNA replication and cell division[edit]

text: 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

text: 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.

text: 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

text: Molecular inheritance[edit]

text: 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

text: 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; genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them. This is known as genetic linkage.[58]

text: Molecular evolution[edit]

text: Mutation[edit]

text: 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

text: 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.

text: 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

text: Sequence homology[edit]

text: 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]

text: 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]

text: Origins of new genes[edit]

text: 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

text: "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]

text: 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]

text: Genome[edit]

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

text: Number of genes[edit]

text: 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]

text: 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 .

text: Essential genes[edit]

text: 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]

text: 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.

text: Genetic and genomic nomenclature[edit]

text: 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]

text: Genetic engineering[edit]

text: 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]

text: 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.

text: 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.


document_title: You Ain't Goin' Nowhere

question_text: meaning of you ain't going nowhere lyrics

question_tokens: meaning of you ai n 't going nowhere lyrics

root

text: You Ain't Goin' Nowhere

text: Bob Dylan's versions[edit]

text: 1967 versions[edit]

text: Starting in June 1967 and ending in October 1967, Bob Dylan's writing and recording sessions with the Band (then known as the Hawks) in Woodstock, New York, were the source of many new songs that were circulated as demos by Dylan's publisher for fellow artists to record.[9] "You Ain't Goin' Nowhere" was written and recorded during this period and features lyrics that allude to the singer waiting for his bride to arrive and possibly, a final premarital fling.[10] The original version found on 1975's The Basement Tapes album was recorded with the Band (minus Levon Helm who had temporarily left the group at this point) in the basement of their house in West Saugerties, New York, called "Big Pink". A first take recorded during the Basement Tapes sessions includes improvised nonsense lyrics such as "Just pick up that oil cloth, cram it in the corn / I don't care if your name is Michael / You're gonna need some boards / Get your lunch, you foreign bib".[11] This alternate take was released in 2014 on The Bootleg Series Vol. 11: The Basement Tapes Complete.

tag: p

text: 1971 version[edit]

text:
"You Ain't Goin' Nowhere (1971 version)"

The 1971 version of "You Ain't Goin' Nowhere", recorded with Happy Traum and released on Bob Dylan's Greatest Hits Vol. II.

Problems playing this file? See media help.

tag: table

text: On September 24, 1971, Dylan re-recorded three songs from the Basement Tapes sessions for inclusion on his Greatest Hits Vol. II album—"You Ain't Goin' Nowhere", "I Shall Be Released", and "Down in the Flood"—with Happy Traum playing bass, banjo and electric guitar, as well as providing vocal harmony.[12] Traum notes that "they were very popular songs ... that [Dylan] wanted to put his own stamp on."[13] The lyrics of this performance of "You Ain't Goin' Nowhere" differed significantly from both the Basement Tapes versions, and also played upon a mistaken lyric in The Byrds' cover of three years earlier (see below).[14] The 1971 version was later released on the compilations The Essential Bob Dylan (2000) and Dylan (2007), although the latter album's liner notes erroneously state that it is the 1967 version.[15][16]

text: The Byrds' version[edit]

text:
"You Ain't Goin' Nowhere"

1968 Dutch picture sleeve.

Single by The Byrds

from the album Sweetheart of the Rodeo

B-side
"Artificial Energy"

Released
April 2, 1968

Format
7" single

Recorded
March 9, 1968

Studio
Columbia Studios, Nashville, Tennessee

Genre
Country rock

Length
2:33

Label
Columbia

Songwriter(s)
Bob Dylan

Producer(s)
Gary Usher

The Byrds singles chronology

"Goin' Back"
(1967)
"You Ain't Goin' Nowhere"
(1968)
"I Am a Pilgrim"
(1968)

"Goin' Back"
(1967)
"You Ain't Goin' Nowhere"
(1968)
"I Am a Pilgrim"
(1968)

text: The Byrds' recording of "You Ain't Goin' Nowhere" was released as a single on April 2, 1968, some three years prior to any commercial release of the song by Dylan.[3][6][7] It was the lead single from The Byrds' 1968 country rock album, Sweetheart of the Rodeo, and reached number 74 on the Bllboard Hot 100 chart and number 45 on the UK Singles Chart.[6][17][18] Along with the then current line-up of The Byrds, the song also features musical contributions from session musician Lloyd Green on pedal steel guitar.[14] Although it is not as famous as their cover version of "Mr. Tambourine Man", The Byrds' recording of "You Ain't Goin' Nowhere" is often considered by critics to be the band's best Dylan cover.[19]

text: The song was selected as a suitable cover by The Byrds after their record label, Columbia Records, sent them some demos from Dylan's Woodstock sessions.[20] Included among these demos were the songs "You Ain't Goin' Nowhere" and "Nothing Was Delivered", both of which were recorded by The Byrds in March 1968, during the Nashville recording sessions for Sweetheart of the Rodeo.[5][14] Despite the change in musical style that the country-influenced Sweetheart of the Rodeo album represented for The Byrds, the inclusion of two Dylan covers on the album forged a link with their previous folk rock incarnation, when Dylan's material had been a mainstay of their repertoire.[21]

text: The Byrds' recording of the song caused a minor controversy between the band and its author. Dylan's original demo of "You Ain't Goin' Nowhere" contained the lyric "Pick up your money, pack up your tent", which was mistakenly altered in The Byrds' version, by guitarist and singer Roger McGuinn, to "Pack up your money, pick up your tent".[22] Dylan expressed mock-annoyance at this lyric change in his 1971 recording of the song, singing "Pack up your money, put up your tent McGuinn/You ain't goin' nowhere."[14] McGuinn replied in 1989 on a new recording of the song included on the Nitty Gritty Dirt Band's Will the Circle Be Unbroken: Volume Two album, adding the word "Dylan" after the same "Pack up your money, pick up your tent" lyric.[23] McGuinn and the Nitty Gritty Dirt Band's 1989 recording of the song, which also featured The Byrds' former bass player Chris Hillman, was released as a single and peaked at number six on the Billboard Hot Country Singles chart in 1989,[23] as well as number eleven on the Canadian country music charts published by RPM.[24] In spite of the involvement of the Nitty Gritty Dirt Band, the single release was credited to McGuinn and Hillman alone.[25]

text: After its appearance on Sweetheart of the Rodeo, the song would go on to become a staple of The Byrds' live concert repertoire, until their final disbandment in 1973.[26] The Byrds re-recorded "You Ain't Goin' Nowhere" in 1971 with Earl Scruggs, as part of the Earl Scruggs, His Family and Friends television special, and this version was included on the program's accompanying soundtrack album.[27] The song was also performed live by a reformed line-up of The Byrds featuring Roger McGuinn, David Crosby, and Chris Hillman in January 1989.[26] McGuinn continues to perform the song in his solo concerts and consequently it appears on his 2007 album, Live from Spain.[28]

text: In addition to its appearance on the Sweetheart of the Rodeo album, The Byrds' original recording of "You Ain't Goin' Nowhere" also appears on several of the band's compilations, including The Best of The Byrds: Greatest Hits, Volume II, History of The Byrds, The Byrds Play Dylan, The Original Singles: 1967–1969, Volume 2, The Byrds, and There Is a Season.[19] Live performances of the song are included on the expanded edition of The Byrds' (Untitled) album and on Live at Royal Albert Hall 1971.[19]

text: Other covers[edit]

text: The British beat group Unit 4 + 2 released a recording of "You Ain't Goin' Nowhere" as a single in 1968 but it suffered poor sales as a result of the version released by The Byrds[29] and consequently it did not chart.[30] Joan Baez included a gender-switched version of the song, in which she sings "Tomorrow's the day my man's gonna come", on her 1968 album of Dylan covers, Any Day Now.[31] Australian band The Flying Circus included this song on their self-titled debut album released in August 1969.

text: Roots rock quartet The Rave-Ups covered the song on their 1985 album, Town and Country.[32] Shawn Colvin, Mary Chapin Carpenter, and Rosanne Cash also performed the song at Madison Square Garden in 1992, for eventual release on the Bob Dylan tribute album The 30th Anniversary Concert Celebration.[33]

text: Phish covered the song during their July 30, 2003 concert at the Tweeter Center at the Waterfront in Camden, New Jersey. This is the only time that Phish has performed the song, coming in the show before their IT music festival in Maine (particular emphasis was put on the lyric "We'll climb that hill, no matter how steep...when we get up to it.")[34]

text: The Crust Brothers covered "You Ain't Goin' Nowhere" on their 1998 live album, Marquee Mark[35] and Counting Crows recorded the song as a bonus track on their Hard Candy album in 2002 as well as performing it live with Augustana.[36][37] Maria Muldaur recorded the song, with slightly altered lyrics, on her 2006 Heart of Mine: Maria Muldaur Sings Love Songs of Bob Dylan album[38] and Marty Raybon, former vocalist of Shenandoah, also covered the song on his 2006 album, When the Sand Runs Out.[39]

text: Glen Hansard and Markéta Irglová recorded the song for the soundtrack album to Todd Haynes' Dylan biopic, I'm Not There, using the lyrics from Dylan's 1971 version, including the reference to Roger McGuinn.[40] The Dandy Warhols have covered the song on the 2009 digital download edition of their album The Dandy Warhols Are Sound[41] and for their September 1, 2011 Daytrotter session. Actor Oscar Isaac (with Kate Mara and Chad Fischer) performed a version of the song in the 2011 film 10 Years, which also appeared on the film's soundtrack.[42] In 2012, Brett Dennen released a version of "You Ain't Goin' Nowhere" on the Chimes of Freedom: Songs of Bob Dylan Honoring 50 Years of Amnesty International album.

text: Garth Brooks for the 2013 "The Melting Pot" album in the Blame It All on My Roots: Five Decades of Influences compilation.

text: Slovenian singer-songwriter Matej Krajnc recorded his own version of the song, translated to Slovenian language with the title "Ostani, kjer si", on his album "Pot skoz kamnolom - pesmi Boba Dylana" in 2017.

text: The track features on the Fairport Convention album Cropredy 2002.

text: Chart performance[edit]

text: The Byrds version[edit]

text:
Chart (1968)
Peak
position

Canadian RPM Top Singles
55[43]

U.S. Billboard Hot 100
74[17]

UK Singles Chart
45[18]

text: Chris Hillman/Roger McGuinn version[edit]

text:
Chart (1989)
Peak
position

Canada Country Tracks (RPM)[44]
11

US Hot Country Songs (Billboard)[45]
6

text: Year-end charts[edit]

text:
Chart (1989)
Position

US Country Songs (Billboard)[46]
79


document_title: Prime Suspect 1973

question_text: who played jane tennison in prime suspect 1973

text: Prime Suspect 1973

text: Synopsis[edit]

text: Set in Hackney, the series depicts a 22-year-old Jane Tennison (Stefanie Martini) as she begins her career as a WPC with the Metropolitan Police Service in 1973. At a time when women were beginning to be gradually integrated into the police force, Tennison has to deal with sexism, as well as difficulties in her home life as her family disapprove of her career choice. Under the guidance of DI Len Bradfield (Sam Reid), the naive and inexperienced Tennison assists in investigating the murder of a young runaway, Julie-Ann Collins. Meanwhile, criminal Clifford Bentley (Alun Armstrong) is released from prison and, along with other members of his family, is planning a bank heist. Links to Collins's murder threaten to expose the Bentley family's plans.

text: Cast[edit]

text: Main cast[edit]

text:
Stefanie Martini as WPC Jane Tennison
Sam Reid as DI Len Bradfield
Blake Harrison as DS Spencer Gibbs
Alun Armstrong as Clifford Bentley
Ruth Sheen as Renee Bentley
Jessica Gunning as WPC Kath Morgan
Andrew Brooke as Sergeant Harris

tag: ul

text: Supporting cast[edit]

text:
Nick Sidi as Andrew Tennison
Geraldine Somerville as Joyce Tennison
Geoffrey Streatfeild as George Collins
Nancy Carroll as Mary Collins
Rosie Day as Pam Tennison
Lex Shrapnel as John Bentley
Jay Taylor as David Bentley
Jacob James Beswick as Eddie Philips
Joshua Hill as DC Edwards
Daniel Ezra as DC Ashton
Tommy McDonnell as DC Hudson
Jordan Long as DS Lawrence

text: Episodes[edit]

text:
No.TitleDirected byWritten byOriginal air dateUK viewers(millions) 1"Episode 1"David CaffreyGlen Laker2 March 2017 (2017-03-02)7.64
A young prostitute, Julie-Ann Collins, is found murdered in an underpass on a busy London estate. New recruit WPC Jane Tennison is drawn into the investigation, led by DI Len Bradfield, as the search for Julie-Ann's killer gets underway. Suspicion initially falls on her boyfriend, Eddie Phillips, who has no alibi for the time of the murder. Meanwhile, career criminal Clifford Bentley is planning a bank robbery from within prison, with help from his sons, John and David.
2"Episode 2"David CaffreyGlen Laker9 March 2017 (2017-03-09)6.64
The search for Julie-Ann's killer continues, as the team try to track her movements from the day she left hospital until the day she was found dead. Tennison uncovers a vital clue which suggests that despite her parents' claims that they had not seen or spoken to Julie-Ann for several months, she contacted them shortly before she was murdered. Tennison also finds the vehicle matching an eye-witness description in the Collins' garage.
3"Episode 3"David CaffreyGlen Laker16 March 2017 (2017-03-16)5.90
Evidence discovered in the basement of the Collins' house suggests that Julie-Ann was beaten by one of her parents. The search for the mysterious 'Oz' continues, until Tennison's perseverance results in a major breakthrough. Meanwhile, Clifford Bentley is out of jail and determined to carry out his final heist. Bradfield, however, warns him that he is keeping a close eye. The brewing sexual spark between Tennison and Bradfield becomes talk of the station.
4"Episode 4"David CaffreyGlen Laker23 March 2017 (2017-03-23)6.02
Following the arrest of the mysterious 'Oz', the investigation takes an unexpected twist. The Bentleys' plans are nearly blown out of the water by a visit from the police. Tennison gets a new lead that could bring the Bentleys into the murder investigation.
5"Episode 5"David CaffreyGlen Laker30 March 2017 (2017-03-30)5.62
Tennison plays the radio recordings to Bradfield who, sensing a chance to get his revenge on Clifford, diverts the team to carry out surveillance of the Bentleys, despite orders from his superior officer to stay focused on the murder case.
6"Episode 6"David CaffreyGlen Laker6 April 2017 (2017-04-06)5.72
In the aftermath of the explosion at the bank vault, the police operation descends into pandemonium and panic. As Tennison arrives at the scene, she is met with the news that Bradfield is dead from the explosion. At a search of the Bentley lock-up, Tennison uncovers evidence that it was where Julie-Ann was killed. The Bentleys' van is searched and a small silk bow is discovered which matches Julie-Ann’s bra. The police manhunt ramps up, with David Bentley now as their prime suspect. Tennison gets to the truth of what really happened.

text: Production[edit]

text: Development[edit]

text: The series is produced for ITV by Noho Film and Television, and was adapted by Glen Laker from the novel Tennison, written by original series creator Lynda La Plante.[1] Commissioned by ITV in June 2015 under the working title Tennison, the series was set to be penned by LaPlante, who had also written the original Prime Suspect novels, and contributed to episodes of the long-running television series of the same name.[2] The announcement of Martini as Jane Tennison, as well as further casting was announced in July 2016.[3] In early 2016, La Plante pulled out of the project, following a disagreement with ITV over aspects of the series, including the casting of certain characters, Tennison in particular.[4] Vera and Home Fires writer Glen Laker was drafted in to write the series.

text: Filming[edit]

text: Filming began in July 2016 in London.[3]

text: Cancellation[edit]

text: In June 2017, ITV confirmed that the series had not been recommissioned, despite high ratings for the first season.[5] The cause is reported to be creative differences between author Lynda LaPlante and ITV. [6]

text: Broadcast[edit]

text: Prime Suspect 1973 first aired on 2 March 2017 on ITV. Internationally, broadcast under the title Prime Suspect: Tennison, the series premiered in South Africa on 6 April 2017 on ITV Choice.[7] The series premiered in the United States on 25 June 2017 on Masterpiece Mystery on PBS, airing over three 90-minute instalments.[8] In Australia, the series is set to be broadcast on ABC on 21 July 2017, under its original title.[9]

text: Reception[edit]

text: The series received mixed reviews from critics, achieving a 50% approval rating based on 12 reviews as aggregated on Rotten Tomatoes.[10] Critics praised Stefanie Martini's performance and the period detail, in particular.[11][12][13] Upon its broadcast in the United States, the Washington Post recommended it as "one of the best shows you’ll find on TV this summer", while the Los Angeles Times said that "Tennison does not quite measure up to Prime Suspect."[14][15] In contrast, Salon considered it fortunate that the series was forced into early retirement, and noted that this Tennison prequel failed to focus on Tennison's character development with the same intensity as the "provocative... classic" sequel did with Helen Mirren's character.[16]