This stylistic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). The chromosome is X-shaped because it is dividing. Introns are regions often found in eukaryote genes that are removed in the splicing process (after the DNA is transcribed into RNA): Only the exons encode the protein. This diagram labels a region of only 50 or so bases as a gene. In reality, most genes are hundreds of times larger.

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a polypeptide or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains. Genes hold the information to build and maintain an organism's cells and pass genetic traits to offspring, although some organelles (e.g. mitochondria) are self-replicating and are not coded for by the organism's DNA. All organisms have many genes corresponding to various biological traits, some of which are immediately visible, such as eye color or number of limbs, and some of which are not, such as blood type or increased risk for specific diseases, or the thousands of basic biochemical processes that comprise life.

The chemical structure of a four-base fragment of a DNA double helix.

A modern working definition of a gene is "a locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions, and or other functional sequence regions ".^[1][2] Colloquial usage of the term gene (e.g. "good genes", "hair color gene") may actually refer to an allele: a gene is the basic instruction—a sequence of nucleic acids (DNA or, in the case of certain viruses RNA), while an allele is one variant of that gene. Referring to having a gene for a trait is no longer the scientifically accepted usage. In most cases, all people would have a gene for the trait in question, but certain people will have a specific allele of that gene, which results in the trait variant. Further, genes code for proteins, which might result in identifiable traits, but it is the gene, not the trait, which is inherited.

Physical definitions[link]

RNA genes and genomes[link]

When proteins are manufactured, the gene is first copied into RNA as an intermediate product. In other cases, the RNA molecules are the actual functional products. For example, RNAs known as ribozymes are capable of enzymatic function, and microRNA has a regulatory role. The DNA sequences from which such RNAs are transcribed are known as RNA genes.

Some viruses store their entire genomes in the form of RNA, and contain no DNA at all. Because they use RNA to store genes, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription. On the other hand, RNA retroviruses, such as HIV, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized. In 2006, French researchers came across a puzzling example of RNA-mediated inheritance in mice. Mice with a loss-of-function mutation in the gene Kit have white tails. Offspring of these mutants can have white tails despite having only normal Kit genes. The research team traced this effect back to mutated Kit RNA.^[3] While RNA is common as genetic storage material in viruses, in mammals in particular RNA inheritance has been observed very rarely.

Functional structure of a gene[link]

Diagram of the "typical" eukaryotic protein-coding gene. Promoters and enhancers determine what portions of the DNA will be transcribed into the precursor mRNA (pre-mRNA). The pre-mRNA is then spliced into messenger RNA (mRNA) which is later translated into protein.

The vast majority of living organisms encode their genes in long strands of DNA. DNA (deoxyribonucleic acid) 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. The most common form of DNA in a cell is in a double helix structure, in which two individual DNA strands twist around each other in a right-handed spiral. In this structure, the base pairing rules specify that guanine pairs with cytosine and adenine pairs with thymine. The base pairing between guanine and cytosine forms three hydrogen bonds, whereas the base pairing between adenine and thymine forms two hydrogen bonds. The two strands in a double helix must therefore be complementary, that is, their bases must align such that the adenines of one strand are paired with the thymines of the other strand, and so on.

Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose; this is known as the 3' end of the molecule. The other end contains an exposed phosphate group; this is the 5' end. The directionality of DNA is vitally important to many cellular processes, since double helices are necessarily directional (a strand running 5'-3' pairs with a complementary strand running 3'-5'), and processes such as DNA replication occur in only one direction. All nucleic acid synthesis in a cell occurs in the 5'-3' direction, because new monomers are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile.

The expression of genes encoded in DNA begins by transcribing the gene into RNA, a second type of nucleic acid that is very similar to DNA, but whose monomers contain the sugar ribose rather than deoxyribose. RNA also contains the base uracil in place of thymine. RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three-nucleotide sequences called codons, which serve as the words in the genetic language. The genetic code specifies the correspondence during protein translation between codons and amino acids. The genetic code is nearly the same for all known organisms.

All genes have regulatory regions in addition to regions that explicitly code for a protein or RNA product. A regulatory region shared by almost all genes is known as the promoter, which provides a position that is recognized by the transcription machinery when a gene is about to be transcribed and expressed. A gene can have more than one promoter, resulting in RNAs that differ in how far they extend in the 5' end.^[4] Although promoter regions have a consensus sequence that is the most common sequence at this position, some genes have "strong" promoters that bind the transcription machinery well, and others have "weak" promoters that bind poorly. These weak promoters usually permit a lower rate of transcription than the strong promoters, because the transcription machinery binds to them and initiates transcription less frequently. Other possible regulatory regions include enhancers, which can compensate for a weak promoter. Most regulatory regions are "upstream"—that is, before or toward the 5' end of the transcription initiation site. Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters.

Many prokaryotic genes are organized into operons, or groups of genes whose products have related functions and which are transcribed as a unit. By contrast, eukaryotic genes are transcribed only one at a time, but may include long stretches of DNA called introns which are transcribed but never translated into protein (they are spliced out before translation). Splicing can also occur in prokaryotic genes, but is less common than in eukaryotes.^[5]

Chromosomes[link]

The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes; the region of the chromosome at which a particular gene is located is called its locus. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. Prokaryotes—bacteria and archaea—typically store their genomes on a single large, circular chromosome, sometimes supplemented by additional small circles of DNA called plasmids, which usually encode only a few genes and are easily transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer. Although some simple eukaryotes also possess plasmids with small numbers of genes, the majority of eukaryotic genes are stored on multiple linear chromosomes, which are packed within the nucleus in complex with storage proteins called histones. The manner in which DNA is stored on the histone, as well as chemical modifications of the histone itself, are regulatory mechanisms governing whether a particular region of DNA is accessible for gene expression. The ends of eukaryotic chromosomes are capped by long stretches of repetitive sequences called telomeres, which do not code for any gene product but are present to prevent degradation of coding and regulatory regions during DNA replication. The length of the telomeres tends to decrease each time the genome is replicated in preparation for cell division; the loss of telomeres has been proposed as an explanation for cellular senescence, or the loss of the ability to divide, and by extension for the aging process in organisms.^[6]

Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain so-called "junk DNA", or regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas the genomes of complex multicellular organisms, including humans, contain an absolute majority of DNA without an identified function.^[7] However it now appears 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.^[2]

Gene expression[link]

In all organisms, there are two major steps separating a protein-coding gene from its protein: First, the DNA on which the gene resides must be transcribed from DNA to messenger RNA (mRNA); and, second, it must be translated from mRNA to protein. RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule itself is called a gene product.

Genetic code[link]

The genetic code is the set of chemical symbols by which a gene is translated into a functional protein. Each gene consists of a specific sequence of nucleotides encoded in a DNA (or sometimes RNA in some viruses^[8]) strand; a correspondence between nucleotides, the basic building blocks of genetic material, and amino acids, the basic building blocks of proteins, must be established for genes to be successfully translated into functional proteins. Sets of three nucleotides, known as codons, each correspond to a specific amino acid or to a signal; three codons are known as "stop codons" and, instead of specifying a new amino acid, alert the translation machinery that the end of the gene has been reached. There are 64 possible codons (four possible nucleotides at each of three positions, hence 4³ possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms.

Transcription[link]

The process of genetic transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed. The DNA strand whose sequence matches that of the RNA is known as the coding strand and the strand from which the RNA was synthesized is the template strand. Transcription is performed by an enzyme called an RNA polymerase, which reads the template strand in the 3' to 5' direction and synthesizes the RNA from 5' to 3'. To initiate transcription, the polymerase first recognizes and binds a promoter region of the gene. Thus a major mechanism of gene regulation is the blocking or sequestering of the promoter region, either by tight binding by repressor molecules that physically block the polymerase, or by organizing the DNA so that the promoter region is not accessible.

In prokaryotes, transcription occurs in the cytoplasm; for very long transcripts, translation may begin at the 5' end of the RNA while the 3' end is still being transcribed. In eukaryotes, transcription necessarily occurs in the nucleus, where the cell's DNA is sequestered; the RNA molecule produced by the polymerase is known as the primary transcript and must undergo post-transcriptional modifications before being exported to the cytoplasm for translation. The splicing of introns present within the transcribed region is a modification unique to eukaryotes; alternative splicing mechanisms can result in mature transcripts from the same gene having different sequences and thus coding for different proteins. This is a major form of regulation in eukaryotic cells.

Translation[link]

Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein. Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds. The genetic code is read three nucleotides at a time, in units called codons, via interactions with specialized RNA molecules called transfer RNA (tRNA). Each tRNA has three unpaired bases known as the anticodon that are complementary to the codon it reads; the tRNA is also covalently attached to the amino acid specified by the complementary codon. When the tRNA binds to its complementary codon in an mRNA strand, the ribosome ligates its amino acid cargo to the new polypeptide chain, which is synthesized from amino terminus to carboxyl terminus. During and after its synthesis, the new protein must fold to its active three-dimensional structure before it can carry out its cellular function.

DNA replication and inheritance[link]

The growth, development, and reproduction of organisms relies on cell division, or the process by which a single cell divides into two usually identical daughter cells. This requires first making a duplicate copy of every gene in the genome in a process called DNA replication. The copies are made by specialized enzymes known as DNA polymerases, which "read" one strand of the double-helical DNA, known as the template strand, and synthesize a new complementary strand. Because the DNA double helix is held together by base pairing, the sequence of one strand completely specifies the sequence of its complement; hence only one strand needs to be read by the enzyme to produce a faithful copy. The process of DNA replication is semiconservative; that is, the copy of the genome inherited by each daughter cell contains one original and one newly synthesized strand of DNA.^[9]

After DNA replication is complete, the cell must physically separate the two copies of the genome and divide into two distinct membrane-bound cells. In prokaryotes - bacteria and archaea - this usually occurs via a relatively simple process called binary fission, in which each circular genome attaches to the cell membrane and is separated into the daughter cells as the membrane invaginates to split the cytoplasm into two membrane-bound portions. Binary fission is extremely fast compared to the rates of cell division in eukaryotes. Eukaryotic cell division is a more complex process known as the cell cycle; DNA replication occurs during a phase of this cycle known as S phase, whereas the process of segregating chromosomes and splitting the cytoplasm occurs during M phase. In many single-celled eukaryotes such as yeast, reproduction by budding is common, which results in asymmetrical portions of cytoplasm in the two daughter cells.

Molecular inheritance[link]

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

During the process of meiotic cell division, an event called genetic recombination or crossing-over can sometimes occur, in which a length of DNA on one chromatid is swapped with a length of DNA on the corresponding sister chromatid. This has no effect if the alleles on the chromatids are the same, but results in reassortment of otherwise linked alleles if they are different. The Mendelian principle of independent assortment asserts that each of a parent's two genes for each trait will sort independently into gametes; which allele an organism inherits for one trait is unrelated to which allele it inherits for another trait. This is in fact only true for genes that do not reside on the same chromosome, or are located very far from one another on the same chromosome. The closer two genes lie on the same chromosome, the more closely they will be associated in gametes and the more often they will appear together; genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them. This is known as genetic linkage.

History[link]

Gregor Mendel

The notion of a gene^[10] is evolving with the science of genetics, which began when Gregor Mendel noticed that biological variations are inherited from parent organisms as specific, discrete traits. The biological entity responsible for defining traits was later termed a gene, but the biological basis for inheritance remained unknown until DNA was identified as the genetic material in the 1940s. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which proposes that the traits of the parents blend or mix in a smooth, continuous gradient in the offspring. Although Mendel's work was largely unrecognized after its first publication in 1866, it was rediscovered in 1900 by three European scientists, Hugo de Vries, Carl Correns, and Erich von Tschermak, who had reached similar conclusions from their own research. However, these scientists were not yet aware of the identity of the 'discrete units' on which genetic material resides.

The existence of genes was first suggested by Gregor Mendel (1822–1884), who, in the 1860s, studied inheritance in peaplants (Pisum sativum) and hypothesized a factor that conveys traits from parent to offspring. He spent over 10 years of his life on one experiment. Although he did not use the term gene, he explained his results in terms of inherited characteristics. Mendel was also the first to hypothesize independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the difference between what would later be described as genotype (the genetic material of an organism) and phenotype (the visible traits of that organism).

Charles Darwin used the term Gemmule to describe a microscopic unit of inheritance, and what would later become known as Chromosomes had been observed separating out during cell division by Wilhelm Hofmeister as early as 1848. The idea that chromosomes are the carriers of inheritance was expressed in 1883 by Wilhelm Roux. Darwin also coined the word pangenesis by (1868).^[11] The word pangenesis is made from the Greek words pan (a prefix meaning "whole", "encompassing") and genesis ("birth") or genos ("origin").

Mendel's concept was given a name by Hugo de Vries in 1889, in his book Intracellular Pangenesis; although probably unaware of Mendel's work at the time, he coined the term "pangen" for "the smallest particle [representing] one hereditary characteristic".^[12] Danish botanist Wilhelm Johannsen coined the word "gene" ("gen" in Danish and German) in 1909 to describe the fundamental physical and functional units of heredity,^[13] while the related word genetics was first used by William Bateson in 1905.^[14] He derived the word from de Vries' "pangen". In the early 1900s, Mendel's work received renewed attention from scientists. In 1910, Thomas Hunt Morgan showed that genes reside on specific chromosomes. He later showed that genes occupy specific locations on the chromosome. With this knowledge, Morgan and his students began the first chromosomal map of the fruit fly Drosophila. In 1928, Frederick Griffith showed that genes could be transferred. In what is now known as Griffith's experiment, injections into a mouse of a deadly strain of bacteria that had been heat-killed transferred genetic information to a safe strain of the same bacteria, killing the mouse.

A series of subsequent discoveries led to the realization decades later that chromosomes within cells are the carriers of genetic material, and that they are made of DNA (deoxyribonucleic acid), a polymeric molecule found in all cells on which the 'discrete units' of Mendelian inheritance are encoded. In 1941, George Wells Beadle and Edward Lawrie Tatum showed that mutations in genes caused errors in specific steps in metabolic pathways. This showed that specific genes code for specific proteins, leading to the "one gene, one enzyme" hypothesis.^[14] Oswald Avery, Colin Munro MacLeod, and Maclyn McCarty showed in 1944 that DNA holds the gene's information.^[15] In 1953, James D. Watson and Francis Crick demonstrated the molecular structure of DNA. Together, these discoveries 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.

In 1972, Walter Fiers and his team at the Laboratory of Molecular Biology of the University of Ghent (Ghent, Belgium) were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein.^[16] Richard J. Roberts and Phillip Sharp discovered in 1977 that genes can be split into segments. This led to the idea that one gene can make several proteins. Recently (as of 2003–2006), biological results let the notion of gene appear more slippery. In particular, genes do not seem to sit side by side on DNA like discrete beads. Instead, regions of the DNA producing distinct proteins may overlap, so that the idea emerges that "genes are one long continuum".^[1] It was first hypothesized in 1986 by Walter Gilbert that neither DNA nor protein would be required in such a primitive system as that of a very early stage of the earth if RNA could perform as simply a catalyst and genetic information storage processor.

The modern study of genetics at the level of DNA is known as molecular genetics and the synthesis of molecular genetics with traditional Darwinian evolution is known as the modern evolutionary synthesis.

Mendelian inheritance and classical genetics[link]

Crossing between two pea plants heterozygous for purple (B, dominant) and white (b, recessive) blossoms

According to the theory of Mendelian inheritance, variations in phenotype—the observable physical and behavioral characteristics of an organism—are due to variations in genotype, or the organism's particular set of genes, each of which specifies a particular trait. Different forms of a gene, which may give rise to different phenotypes, are known as alleles. Organisms such as the pea plants Mendel worked on, along with many plants and animals, have two alleles for each trait, one inherited from each parent. Alleles may be dominant or recessive; dominant alleles give rise to their corresponding phenotypes when paired with any other allele for the same trait, whereas recessive alleles give rise to their corresponding phenotype only when paired with another copy of the same allele. For example, if the allele specifying tall stems in pea plants is dominant over the allele specifying short stems, then pea plants that inherit one tall allele from one parent and one short allele from the other parent will also have tall stems. Mendel's work demonstrated that alleles assort independently in the production of gametes, or germ cells, ensuring variation in the next generation.

Mutation[link]

DNA replication is for the most part extremely accurate, with an error rate per site of around 10⁻⁶ to 10⁻¹⁰ in eukaryotes.^[9] Rare, spontaneous alterations in the base sequence of a particular gene arise from a number of sources, such as errors in DNA replication and the aftermath of DNA damage. These errors are called mutations. The cell contains many DNA repair mechanisms for preventing mutations and maintaining the integrity of the genome; however, in some cases—such as breaks in both DNA strands of a chromosome—repairing the physical damage to the molecule is a higher priority than producing an exact copy. Due to the degeneracy of the genetic code, some mutations in protein-coding genes are silent, or produce no change in the amino acid sequence of the protein for which they code; for example, the codons UCU and UUC both code for serine, so the U↔C mutation has no effect on the protein. Mutations that do have phenotypic effects are most often neutral or deleterious to the organism, but sometimes they confer benefits to the organism's fitness.

Mutations propagated to the next generation lead to variations within a species' population. Variants of a single gene are known as alleles, and differences in alleles may give rise to differences in traits. Although it is rare for the variants in a single gene to have clearly distinguishable phenotypic effects, certain well-defined traits are in fact controlled by single genetic loci. A gene's most common allele is called the wild type allele, and rare alleles are called mutants. However, this does not imply that the wild-type allele is the ancestor from which the mutants are descended.

Genome[link]

Chromosomal organization[link]

The total complement of genes in an organism or cell is known as its genome. In prokaryotes, the vast majority of genes are located on a single chromosome of circular DNA, while eukaryotes usually possess multiple individual linear DNA helices packed into dense DNA-protein complexes called chromosomes. Genes that appear together on one chromosome of one species may appear on separate chromosomes in another species. Many species carry more than one copy of their genome within each of their somatic cells. Cells or organisms with only one copy of each chromosome are called haploid; those with two copies are called diploid; and those with more than two copies are called polyploid. The copies of genes on the chromosomes are not necessarily identical. In sexually reproducing organisms, one copy is normally inherited from each parent.

Number of genes[link]

The human genome, categorized by function of each gene product, given both as number of genes and as percentage of all genes.^[17]

Early estimates of the number of human genes that used expressed sequence tag data put it at 50 000–100 000.^[18] Following the sequencing of the human genome and other genomes, it has been found that rather few genes (~20 000 in human, mouse and fly, ~13 000 in roundworm, >46 000 in rice) encode all the proteins in an organism.^[19] These protein-coding sequences make up 1–2% of the human genome.^[20] A large part of the genome is transcribed however, to introns, retrotransposons and seemingly a large array of noncoding RNAs.^[19][20] Total number of proteins (the Earth's proteome) is estimated to be 5 million sequences.^[21]

Genetic and genomic nomenclature[link]

Gene nomenclature has been established by the HUGO Gene Nomenclature Committee (HGNC) for each known human gene in the form of an approved gene name and symbol (short-form abbreviation). All approved symbols are stored in the HGNC Database. Each symbol is unique and each gene is only given one approved gene symbol. This also facilitates electronic data retrieval from publications. In preference each symbol maintains parallel construction in different members of a gene family and can be used in other species, especially the mouse.

Evolutionary concept of a gene[link]

George C. Williams first explicitly advocated the gene-centric view of evolution in his 1966 book Adaptation and Natural Selection. He proposed an evolutionary concept of gene to be used when we are talking about natural selection favoring some genes. The definition is: "that which segregates and recombines with appreciable frequency." According to this definition, even an asexual genome could be considered a gene, insofar that it have an appreciable permanency through many generations.

The difference is: the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit.

Richard Dawkins' books The Selfish Gene (1976) and The Extended Phenotype (1982) defended the idea that the gene is the only replicator in living systems. This means that only genes transmit their structure largely intact and are potentially immortal in the form of copies. So, genes should be the unit of selection. In The Selfish Gene Dawkins attempts to redefine the word 'gene' to mean "an inheritable unit" instead of the generally accepted definition of "a section of DNA coding for a particular protein". In River Out of Eden, Dawkins further refined the idea of gene-centric selection by describing life as a river of compatible genes flowing through geological time. Scoop up a bucket of genes from the river of genes, and we have an organism serving as temporary bodies or survival machines. A river of genes may fork into two branches representing two non-interbreeding species as a result of geographical separation.

Gene targeting and implications[link]

Gene targeting is commonly referred to techniques for altering or disrupting mouse genes and provides the mouse models for studying the roles of individual genes in embryonic development, human disorders, aging and diseases. The mouse models, where one or more of its genes are deactivated or made inoperable, are called knockout mice. Since the first reports in which homologous recombination in embryonic stem cells was used to generate gene-targeted mice,^[22] gene targeting has proven to be a powerful means of precisely manipulating the mammalian genome, producing at least ten thousand mutant mouse strains and it is now possible to introduce mutations that can be activated at specific time points, or in specific cells or organs, both during development and in the adult animal.^[23][24]

Gene targeting strategies have been expanded to all kinds of modifications, including point mutations, isoform deletions, mutant allele correction, large pieces of chromosomal DNA insertion and deletion, tissue specific disruption combined with spatial and temporal regulation and so on. It is predicted that the ability to generate mouse models with predictable phenotypes will have a major impact on studies of all phases of development, immunology, neurobiology, oncology, physiology, metabolism, and human diseases. Gene targeting is also in theory applicable to species from which totipotent embryonic stem cells can be established, and therefore may offer a potential to the improvement of domestic animals and plants.^[24][25]

Changing concept[link]

The concept of the gene has changed considerably (see history section). From the original definition of a "unit of inheritance", the term evolved to mean a DNA-based unit that can exert its effects on the organism through RNA or protein products. It was also previously believed that one gene makes one protein; this concept was overthrown by the discovery of alternative splicing and trans-splicing.^[14]

The definition of a gene is still changing. The first cases of RNA-based inheritance have been discovered in mammals.^[3] Evidence is also accumulating that the control regions of a gene do not necessarily have to be close to the coding sequence on the linear molecule or even on the same chromosome. Spilianakis and colleagues discovered that the promoter region of the interferon-gamma gene on chromosome 10 and the regulatory regions of the T(H)2 cytokine locus on chromosome 11 come into close proximity in the nucleus possibly to be jointly regulated.^[26]

The concept that genes are clearly delimited is also being eroded. There is evidence for fused proteins stemming from two adjacent genes that can produce two separate protein products. While it is not clear whether these fusion proteins are functional, the phenomenon is more frequent than previously thought.^[27] Even more ground-breaking than the discovery of fused genes is the observation that some proteins can be composed of exons from far away regions and even different chromosomes.^[2][28] This new data has led to an updated, and probably tentative, definition of a gene as "a union of genomic sequences encoding a coherent set of potentially overlapping functional products".^[14] This new definition categorizes genes by functional products, whether they be proteins or RNA, rather than specific DNA loci; all regulatory elements of DNA are therefore classified as gene-associated regions.^[14]

See also[link]

	Biology portal
	Molecular and Cellular Biology portal

References[link]

Further reading[link]

• Dawkins, Richard (1990). The Selfish Gene. Oxford University Press. ISBN 0-19-286092-5.  Google Book Search; first published 1976.
• Dawkins, Richard (1995). River Out of Eden. Basic Books. ISBN 0-465-06990-8. 
• Ridley, Matt (1999). Genome: The Autobiography of a Species in 23 Chapters. Fourth Estate. ISBN 0-00-763573-7. 

External links[link]

Listen to this article (info/dl)

This audio file was created from a revision of the "Gene" article dated 2005-04-21, and does not reflect subsequent edits to the article. (Audio help)

More spoken articles

• Comparative Toxicogenomics Database
• DNA From The Beginning - a primer on genes and DNA
• Genes And DNA - Introduction to genes and DNA aimed at non-biologist
• Entrez Gene - a searchable database of genes
• IDconverter - converts gene IDs between public databases
• iHOP - Information Hyperlinked over Proteins
• TranscriptomeBrowser - Gene expression profile analysis
• The Protein Naming Utility, a database to identify and correct deficient gene names
• Genes - an Open Access journal
• IMPC (International Mouse Phenotyping Consortium) - Encyclopedia of mammalian gene function

Gene Wilder
Wilder at a book signing, May 2007
Born	Jerome Silberman (1933-06-11) June 11, 1933 (age 79) Milwaukee, Wisconsin, U.S.
Nationality	American
Education	Washington High School
Alma mater	University of Iowa
Occupation	Actor, Director, Writer, Author, Activist
Years active	1961–2003
Spouse	Mary Mercier (m. 1960–1965, divorced) Mary Joan Schutz (m. 1967–1974, divorced) Gilda Radner (m. 1984–1989, her death) Karen Boyer (m. 1991–present)
Children	Daughter
Signature

Gene Wilder (born Jerome Silberman; June 11, 1933) is an American stage and screen actor, director, screenwriter, author and activist.

Wilder began his career on stage, making his screen debut in the TV series Armstrong Circle Theatre in 1962. 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 1968 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 Young Frankenstein, a script which garnered 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 has directed and written several of his films, including The Woman in Red (1984).

He was married to actress Gilda Radner. Her 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.^[1]

Since his most recent contribution to acting in 2003, Wilder has turned his attention to writing, producing a memoir in 2005, Kiss Me Like A Stranger: My Search for Love and Art, and the novels My French Whore (2007), The Woman Who Wouldn't (2008), and What Is This Thing Called Love (2010).

Early life and education[link]

Born Jerome Silberman in Milwaukee, Wisconsin on March 11, 1933, Gene Wilder is the son of William J. and Jeanne (Baer) Silberman. He adopted "Gene Wilder" for his professional name at the age of 26, later explaining, "I had always liked Gene because of Thomas Wolfe's character Eugene Gant in Look Homeward, Angel and Of Time and the River. And I was always a great admirer of Thornton Wilder."^[2][3] Wilder first became interested in acting when at age 8, his mother was diagnosed with rheumatic fever and the doctor told him to "try and make her laugh."^[4] When Jeanne Silberman felt that her son's potential was not being fully realized in Wisconsin, she sent him to Black-Foxe, a military institute in Hollywood, where he wrote that he was bullied and sexually assaulted, primarily because he was the only Jewish boy in the school.^[5] After an unsuccessful short stay at Black-Foxe, Wilder returned home and became increasingly involved with the local theatre community. At age fifteen, he performed for the first time in front of a paying audience, as Balthasar (Romeo's manservant) in a production of Shakespeare's Romeo and Juliet.^[6] Gene Wilder graduated from Washington High School located in Milwaukee, Wisconsin in 1951.

Acting career[link]

Early starts: Old Vic and Army[link]

Wilder studied Communication and Theatre Arts at the University of Iowa, where he was a member of the Alpha Epsilon Pi Fraternity.^[7] Following his 1955 graduation from Iowa, he was accepted at the Bristol Old Vic Theatre School in Bristol, England. After six months of studying fencing, Wilder became the first freshman to win the All-School Fencing Championship.^[8] Desiring to study Stanislavski's system, he returned to the U.S., living with his sister and her family in Queens. Wilder enrolled at the HB Studio.^[9]

Wilder was drafted into the Army on September 10, 1956. At the end of recruit training, he was assigned to the medical corps and sent to Fort Sam Houston for training. He was then given the opportunity to choose any post that was open, and wanting to stay near New York City to attend acting classes at the HB Studio, he chose to serve as paramedic in the Department of Psychiatry and Neurology at Valley Forge Army Hospital, in Phoenixville, Pennsylvania.^[10] In November 1957, his mother died from ovarian cancer. He was discharged from the army a year later and returned to New York. A scholarship to the HB Studio allowed him to become a full-time student. At first living on unemployment insurance and some savings, he later supported himself with odd jobs such as a limousine driver and fencing instructor.. Wilder's first professional acting job was in Cambridge, England, where he played the Second Officer in Herbert Berghof's production of Twelfth Night. He also served as a fencing choreographer.^[11]

After three years of study with Berghof and Uta Hagen at the HB Studio, Charles Grodin told Wilder about Lee Strasberg's method acting. Grodin persuaded him to leave the Studio and begin studying with Strasberg in his private class. Several months later, Wilder was accepted into the Actors Studio. Feeling that "Jerry Silberman in Macbeth" did not have the right ring to it, he adopted a stage name.^[12] He chose "Wilder" because it reminded him of Our Town author Thornton Wilder, while "Gene" came from Thomas Wolfe's first novel, Look Homeward, Angel. He also liked "Gene" because as a boy, he was impressed by a distant relative, a World War II bomber navigator who was "handsome and looked great in his leather flight jacket."^[12][13] He later said that he couldn't see Gene Wilder playing Macbeth, either. After joining the Actors Studio, he slowly began to be noticed in the Off Broadway scene, thanks to performances in Sir Arnold Wesker's Roots and in Graham Greene's The Complaisant Lover, for which Wilder received the Clarence Derwent Award for "Best Performance by an Actor in a Nonfeatured Role."

Mel Brooks[link]

In 1963, Wilder was cast in a leading role in Mother Courage and Her Children, a production starring Anne Bancroft, who introduced Wilder to her boyfriend Mel Brooks.^[14] A few months later, Brooks mentioned that he was working on a screenplay called Springtime for Hitler, for which he thought Wilder would be perfect in the role of Leo Bloom. Brooks elicited a promise from Wilder that he would check with him before making any long-term commitments.^[14] Months went by, and Wilder toured the country with different theatre productions, participated in a televised CBS presentation of Death of a Salesman, and was cast for his first role in a film—a minor role in Arthur Penn's 1967 Bonnie and Clyde. After three years of not hearing from Brooks, Wilder was called for a reading with Zero Mostel, who was to be the star of Springtime for Hitler and had approval of his co-star. Mostel approved, and Wilder was cast for his first leading role in a feature film, 1968's The Producers.^[15]

The Producers eventually became a cult comedy classic,^[16][17] with Mel Brooks winning an Academy Award for Best Original Screenplay and Wilder being nominated for an Academy Award for Best Supporting Actor. Nevertheless, Mel Brooks' first directorial effort did not do well at the box office and was not well-received by all critics; New York Times critic Renata Adler reviewed the film and described it as "black college humor."^[18][19]

In 1969, Wilder relocated to Paris, accepting a leading role in Bud Yorkin's Start the Revolution Without Me, a comedy that took place during the French Revolution. After shooting ended, Wilder returned to New York, where he read the script for Quackser Fortune Has a Cousin in the Bronx and immediately called Sidney Glazier, who produced The Producers. Both men began searching for the perfect director for the film. Jean Renoir was the first candidate, but he would not be able to do the film for at least a year, so British-Indian director Waris Hussein was hired.^[20]

[edit] Willy Wonka, Young Frankenstein, and Richard Pryor

In 1971, Mel Stuart offered Wilder the lead role in his film adaptation of Roald Dahl's Charlie and the Chocolate Factory. Wilder was initially hesitant, but finally accepted the role under one condition:

When Stuart asked why, Wilder replied, "because from that time on, no one will know if I'm lying or telling the truth."^[21]

All three films Wilder did after The Producers were box office failures: Start the Revolution and Quackser seemed to audiences poor copies of Mel Brooks films, while Willy Wonka & the Chocolate Factory seemed, to many parents, a moral story "too cruel" for children to understand, thus failing to attract family audiences.^[19] After hearing that Wonka had been a commercial failure, Woody Allen offered Wilder a role in one segment of Everything You Always Wanted to Know About Sex* (*But Were Afraid to Ask). Wilder accepted, hoping this would be the hit to put an end to his series of flops. Everything... was a hit, grossing over $18 million in the United States alone against a $2-million budget.^[22]

Wilder in 1984

After Everything You Always Wanted to Know About Sex* (*But Were Afraid to Ask), Wilder began working on a script he called Young Frankenstein. After he wrote a two-page scenario, he called Mel Brooks, who told him that it seemed like a "cute" idea but showed little interest.^[23] A couple of months later, Wilder received a call from his agent, Mike Medavoy, who asked if he had anything where he could include Peter Boyle and Marty Feldman, his two new clients. Having just seen Feldman on television, Wilder was inspired to write a scene that takes place at Transylvania Station, where Igor and Frederick meet for the first time. The scene was later included in the film almost verbatim. Medavoy liked the idea and called Brooks, asking him to direct. Brooks was not convinced, but having spent four years working on two box office failures, he decided to accept.^[14] While working on the Young Frankenstein script, Wilder was offered the part of the Fox in the musical film adaptation of Saint Exupéry's classic book, The Little Prince. When filming was about to begin in London, Wilder received an urgent call from Mel Brooks, who was filming Blazing Saddles, offering Wilder the role of the "Waco Kid" after Dan Dailey dropped out at the last minute, while Gig Young became too ill to continue. Wilder shot his scenes for Blazing Saddles and immediately afterwards filmed The Little Prince.^[14]

After Young Frankenstein was written, the rights were to be sold to Columbia Pictures, but after having trouble agreeing on the budget, Wilder, Brooks and producer Michael Gruskoff went with 20th Century Fox, where both Brooks and Wilder had to sign five-year contracts. Young Frankenstein was a commercial success, with Wilder and Brooks receiving Best Adapted Screenplay nominations at the 1975 Oscars,^[24] losing to Francis Coppola and Mario Puzo for their adaptation of The Godfather Part II.^[25] While filming Young Frankenstein, Wilder had an idea for a romantic musical comedy about a brother of Sherlock Holmes. Marty Feldman and Madeline Kahn agreed to participate in the project, and Wilder began writing what became his directorial début, 1975's The Adventure of Sherlock Holmes' Smarter Brother.^[26]

In 1975, Wilder's agent sent him a script for a film called Super Chief. Wilder accepted, but told the film's producers that he thought the only person who could keep the film from being offensive was Richard Pryor. Pryor accepted the role in the film, which had been renamed Silver Streak, the first film to team Wilder and Pryor. While filming Silver Streak, Wilder began working on a script for The World's Greatest Lover, inspired by Fellini's The White Sheik. Wilder wrote, produced, and directed The World's Greatest Lover, which premièred in 1977 but was a commercial and critical failure.^[27] The Frisco Kid (1979) would be Wilder's next project. The film was to star John Wayne, but he dropped out when the Warner Brothers executives tried to dissuade him from charging the studio his usual $1-million fee. Harrison Ford, then an up-and-coming actor, was hired for the role.

Sidney Poitier and Gilda Radner[link]

In 1980, Sidney Poitier and producer Hannah Weinstein persuaded Wilder and Richard Pryor to do another film together. Bruce Jay Friedman wrote the script for Stir Crazy, with Poitier directing, for Columbia Pictures. Pryor was struggling with a severe cocaine addiction, and filming became difficult; but once the film premiered, it became an international success. New York magazine listed "Skip Donahue" (Wilder) and "Harry Monroe" (Pryor) # 9 on their 2007 list of "The Fifteen Most Dynamic Duos in Pop Culture History," and the film has often appeared in "best comedy" lists and rankings.^[28][29]

Poitier and Wilder became friends, with the pair working together on a script called Traces—which became 1982's Hanky Panky, the film where Wilder met comedienne Gilda Radner. Through the remainder of the decade, Wilder and Radner worked in several projects together. After Hanky Panky, Wilder directed his third film, 1984's The Woman in Red, which starred Wilder, Radner, and Kelly LeBrock. The Woman in Red was not well-received by the critics, nor was their next project, 1986's Haunted Honeymoon, which failed to attract audiences.

TriStar Pictures wanted to produce another film starring Wilder and Pryor, and Wilder agreed to do See No Evil, Hear No Evil only if he was allowed to rewrite the script. The studio agreed, and See No Evil, Hear No Evil premiered on May 1989 to mostly negative reviews. Many critics praised Wilder and Pryor, and even Kevin Spacey's performance, but they mostly all agreed that the script was terrible. Roger Ebert called it "a real dud";^[30] the Deseret Morning News described the film as "stupid," with an "idiotic script" that had a "contrived story" and too many "juvenile gags";^[31] while Vincent Canby called it "by far the most successful co-starring vehicle for Mr. Pryor and Mr. Wilder," also acknowledging that "this is not elegant movie making, and not all of the gags are equally clever."^[32]

1990s–2000s[link]

After starring as a political cartoon writer who falls in love in the 1990 flop Funny About Love, Wilder did one final film with Richard Pryor, the 1991 box office flop Another You, in which Pryor's physical deterioration from multiple sclerosis was clearly noticeable.^[33] The film marked both Pryor's last starring role in a film (he would appear in a few cameos until his death in 2005) and also marked Wilder's last appearance in a feature film. His remaining work consisted of television movies and guest appearances in TV shows.

In 1994, Wilder starred in the NBC sitcom Something Wilder.^[34] The show received poor reviews and lasted only one season. He went back to the small screen on 1999, appearing in three television movies, one of which was the NBC adaptation of Alice in Wonderland. The other two were mystery movies for A&E television in which Wilder played Larry "Cash" Carter, a theater director turned private eye (those two films were also co-written by Wilder). Three years later, Wilder guest-starred on two episodes of NBC's Will & Grace, winning a Primetime Emmy Award for Outstanding Guest Actor on a Comedy Series for his role as Mr. Stein, Will Truman's boss.^[35]

Personal life[link]

Relationships[link]

Wilder met his first wife, Mary Mercier, while studying at the HB Studio in New York. Although the couple had not been together long, they married on July 22, 1960. They spent long periods of time apart, eventually divorcing in 1965. A few months later, Wilder began dating Mary Joan Schutz, a friend of his sister. Schutz had a daughter, Katharine, from a previous marriage. When Katharine started calling Wilder "Dad," he decided to do what he felt was "the right thing to do,"^[36] marrying Schutz on October 27, 1967 and adopting Katharine that same year. Schutz and Wilder separated after seven years of marriage, with Schutz thinking that Wilder was having an affair with his Young Frankenstein co-star, Madeline Kahn. After the divorce, he briefly dated his other Frankenstein co-star, Teri Garr. Wilder would eventually become estranged from Katharine.^[14][37]

Wilder met Saturday Night Live actress Gilda Radner on August 13, 1981, while filming Sidney Poitier's Hanky Panky. Radner was married to G.E. Smith at the time, but she and Wilder became inseparable friends. When the filming of Hanky ended, Wilder found himself missing Radner, so he called her. The relationship grew, and Radner eventually divorced Smith in 1982. She moved in with Wilder, and the couple married on September 14, 1984, in the south of France. The couple wanted to have children, but Radner suffered miscarriages, and doctors could not determine the problem. After experiencing severe fatigue and suffering from pain in her upper legs on the set of Haunted Honeymoon, Radner sought medical treatment. Following a number of false diagnoses, it was determined that she had ovarian cancer in October 1986.^[38] Over the next year and a half, Radner battled the disease, receiving chemotherapy and radiotherapy treatments. The disease finally went into remission, giving the pair a respite, during which time Wilder filmed See No Evil, Hear No Evil.^[38] By May 1989, the cancer returned and had metastasized. Radner died on May 20, 1989.^[39] Wilder later stated, "I always thought she'd pull through."^[40]

Following Radner's death, Wilder became active in promoting cancer awareness and treatment, helping found the Gilda Radner Ovarian Cancer Detection Center in Los Angeles and co-founding Gilda's Club, a support group to raise awareness of cancer that began in New York City and now has branches throughout the country.^[7]

Semi-retirement and authorship[link]

Wilder at a book signing in May 2007

While preparing for his role as a deaf man in See No Evil, Hear No Evil, Wilder met Karen Webb (née Boyer), who was a clinical supervisor for the New York League for the Hard of Hearing. Webb coached him in lip reading. Following Gilda Radner's death, Wilder and Webb reconnected, and on September 8, 1991, they married.^[40] The two live in Stamford, Connecticut, in the 1734 Colonial home that he shared with Radner. The Wilders spend most of their time painting watercolors, writing, and participating in charitable efforts.^[14] In October 2001, he read from Charlie and the Chocolate Factory as part of a special benefit performance held at the Westport Country Playhouse to aid families affected by the September 11 attacks.^[14][41] Also in 2001, Wilder donated a collection of scripts, correspondences, documents, photographs, and clipped images to the University of Iowa Libraries.^[2]

In 1998, Wilder collaborated on the book Gilda's Disease with oncologist Steven Piver, sharing personal experiences of Radner's struggle with ovarian cancer. Wilder himself was hospitalized with non-Hodgkin lymphoma in 1999, but confirmed in March 2005 that the cancer was in complete remission following chemotherapy and a stem cell transplant.^[14]

On March 1, 2005, Wilder released his highly personal memoir, Kiss Me Like a Stranger: My Search for Love and Art, an account of his life covering everything from his childhood up to Radner's death. Two years later, in March 2007, Wilder released his first novel, My French Whore, which is set during World War I.^[42] His second novel, The Woman Who Wouldn't, was released in March 2008.^[43] In 2010, he released a collection of stories called What is This Thing Called Love?.^[44]

In a 2008, Turner Classic Movies special Role Model: Gene Wilder, where Alec Baldwin interviewed Wilder about his career, Wilder said that he was basically retired from acting for good. "I don't like show business, I realized," he explained. "I like show, but I don't like the business."

An unauthorized biography of Wilder entitled Gene Wilder: Funny and Sad by Brian Scott Mednick was published in December 2010 by BearManor Media.

Work[link]

Film[link]

Television[link]

• Voice for The Electric Company's segment The Adventures of Letterman (60 episodes, 1972–77)
• Something Wilder (1994–95)
• Will & Grace (2002) Episode "Boardroom and a Parked Place" (Guest Star – Mr. Stein)
• Will & Grace (2003) Episode "Sex, Losers & Videotape" (Guest Star – Mr. Stein)

Stage[link]

• The Complaisant Lover (Broadway, 1962)
• Mother Courage and Her Children (Broadway, 1963)
• Death Of A Salesman
• One Flew Over the Cuckoo's Nest (Broadway, 1963)
• The White House (Broadway, 1964)
• Luv (Broadway, 1966)
• The Scarecrow (Broadway, 1972)
• Rhinoceros (1974)
• Laughter on the 23rd Floor (London, 1996)

Publications[link]

• Piver, M. Steven and Gene Wilder. Gilda's Disease: Sharing Personal Experiences and a Medical Perspective on Ovarian Cancer. Broadway Books, 1998. ISBN 0-7679-0138-X.
• Wilder, Gene. Kiss Me Like a Stranger: My Search for Love and Art. St. Martin's Press, 2005. ISBN 0-312-33706-X.
• Wilder, Gene. My French Whore. St. Martin's Press, 2007. ISBN 0-312-36057-6.
• Wilder, Gene. The Woman Who Wouldn't. St. Martin's Press, 2008. ISBN 0-312-37578-6.
• Wilder, Gene. What is this Thing Called Love?. St. Martin's Press, 2010. ISBN 978-0-312-59890-7

References[link]

Bibliography[link]

• Piver, M. Steven and Gene Wilder. Gilda's Disease: Sharing Personal Experiences and a Medical Perspective On Ovarian Cancer. Broadway Books, 1998. ISBN 0-7679-0138-X.
• Radner, Gilda. It's Always Something. Simon and Shuster, 1989. ISBN 0-671-63868-8.
• Wilder, Gene. Kiss Me Like a Stranger: My Search for Love and Art. St. Martin's Press, 2005. ISBN 0-312-33706-X.

External links[link]

• "The Films of Gene Wilder", video compilation of movie clips, 4 minutes
• Gene Wilder at the Internet Movie Database
• Gene Wilder at the Internet Broadway Database
• Gene Wilder at the Internet Off-Broadway Database
• Gene Wilder at the TCM Movie Database
• Gene Wilder at AllRovi

This article is about the fictional character. For the candy company, see, The Willy Wonka Candy Company.

This article has multiple issues. Please help improve it or discuss these issues on the talk page. It needs additional citations for verification. Tagged since February 2009. It needs attention from an expert on the subject. Tagged since February 2011. Its introduction may need to be rewritten to comply with Wikipedia's lead section guidelines. Tagged since February 2011.

Willy Wonka is a major character of Roald Dahl's 1964 children's novel Charlie and the Chocolate Factory and the film adaptations that followed. The book and the 1971 film adaption both vividly depict an eccentric Wonka — a feature arising from his creative genius. He bewilders the other characters with his antics, but Charlie enjoys Wonka's behavior. In the 2005 film adaption, Willy Wonka's behavior is viewed more as a (sympathetic) character flaw.

Appearances[link]

1971 film adaption[link]

Candy maker Willy Wonka has hidden five Golden Tickets amongst his Wonka Bars. The finders of these special tickets will be given a full tour of his tightly guarded candy factory as well as a lifetime supply of chocolate. The contest sets off a global craze with everyone desperately seeking out the tickets. They are eventually found by five different children from around the world.

Wonka greets the winning children and their guardians at the factory gates. He immediately shows his unpredictability by slowly hobbling towards the gate with a cane, then pretending to fall, only to do a somersault and spring back to his feet with a flourish. Once he and his visitors are inside, Wonka requires each to sign a contract before the tour can begin. The tour progresses though many fantastic rooms and labs in the factory, all run by Wonka's crew of Oompa Loompas. Along the way, four of the children misbehave against Wonka's warnings, resulting in serious but comical consequences and removing them from the tour.

Eventually, Charlie Bucket is the only remaining child. Wonka informs him that the tour is over, politely dismisses him and Grandpa Joe, and disappears into his office without mentioning the promised prize of a lifetime supply of chocolate. Grandpa Joe and Charlie enter the office, where Wonka tells them that Charlie does not get the prize because he broke the rules. When questioned on the existence of the said rules, Wonka irritably reveals the forfeiture clause of the contract Charlie signed. Charlie's part in the theft of Fizzy Lifting drinks earlier in the story means that he violated the contract, and therefore he receives nothing. Now seemingly enraged, Wonka again dismisses them with a furious "Good day!".

When Charlie subsequently returns a gobstopper to Wonka that he initially planned to give to an industrial spy, Wonka joyfully tells Charlie that he "won" and begs his guests' forgiveness. He reveals that the spy "Slugworth" is actually an employee named Wilkinson, whose offer to buy the gobstopper was a morality test for the Golden Ticket winners, and Charlie was the only one who passed. Wonka leads Charlie and Joe to the "Wonkavator", a multi-directional glass elevator, and fly out of the factory in it. As they soar over the village, Wonka tells Charlie that his actual prize is not just the chocolate but the factory itself, as the Golden Ticket search was created to help Wonka search for an honest and worthy child to be his heir. Charlie and his family will reside in the factory and take over its operation when Wonka retires.

2005 film adaption[link]

Willy Wonka, the owner of a famous chocolate factory, has long closed access to his factory due to problems concerning industrial espionage that ultimately led him to fire all his employees, among them Charlie's Grandpa Joe. One day, Wonka informs the world of a contest, in which five Golden Tickets have been placed in five random Wonka Bars worldwide, and the winners will be given a full tour of the factory as well as a lifetime supply of chocolate, while one ticket holder will be given a special prize at the end of the tour. After all five of the tickets are found, Wonka greets Charlie and the other ticket holders outside the factory and leads the group into the facility. During the tour, Wonka tempts each of the bad children to disobey his orders with something related to their individual character flaws. Wonka then invites Charlie to come live and work in the factory with him, and reveals that the purpose of the Golden Tickets and the tour was to make the "least rotten" child the heir of the factory itself, so he can have someone carry on his legacy when he dies. The only condition, however, is that Charlie must leave his family behind, because Wonka believes family is a hindrance to a chocolatier's creative freedom, a philosophy Wonka developed due to his dentist father, Dr. Wilbur Wonka, denying his son candy because of the potential risk to his teeth. After secretly sampling some candy, Wonka was instantly hooked and ran away to follow his dreams. After being refused Charlie's offer, Wonka falls into a state of emotional depression and returns to Charlie to seek advice. Wonka soon reunites with his estranged father and allows Charlie's family to live in the factory, forever.

Concept and creation[link]

2005 film adaption[link]

Early on in the production of the 2005 film, Nicolas Cage was under discussions for portraying Willy Wonka, but lost interest.^[1][2] Warner Bros. president Alan F. Horn wanted Tom Shadyac to direct Jim Carrey as Willy Wonka, believing the duo could make Charlie and the Chocolate Factory relevant to mainstream audiences, but Roald Dahl's widow Liccy Dahl opposed this.^[3] After Tim Burton was hired as director in May 2003, Burton immediately thought of Johnny Depp for the role of Willy Wonka, who joined the following August for his fourth collaboration with the director.^[4]

Burton and screenwriter John August worked together in creating Wilbur Wonka, Willy's domineering dentist father. "You want a little bit of the flavor of why Wonka is the way he is," Burton reasoned. "Otherwise, what is he? He's just a weird guy."^[5] Warner Bros. and Burton held differences over the characterization of Willy Wonka. The studio wanted to make Willy Wonka the idyllic father figure Charlie Bucket had longed for his entire life. Burton believed that Wonka would not be a good father, finding the character similar to a recluse.^[6] "In some ways," Burton protested, "he's more screwed up than the kids."^[7] Prior to Burton's involvement, Warner Bros. considered or discussed Willy Wonka with Nicolas Cage, Jim Carrey, Michael Keaton,^[1] Brad Pitt, Will Smith^[5] and Adam Sandler.^[3] Johnny Depp was the only actor Burton considered for the role,^[7] who signed on without reading the script under the intention on going with a completely different approach than what Gene Wilder did in the 1971 film adaptation.^[8] "Regardless of what one thinks of that film," Depp explained, "Gene Wilder's persona, his character, stands out."^[3] Reportedly, Depp cited Marilyn Manson as his inspiration for his portrayal of Wonka.

Comparisons were drawn between Willy Wonka and musician Michael Jackson. Burton joked, "Here's the deal. There's a big difference: Michael Jackson (d. 2009) likes children, Willy Wonka can't stand them. To me that's a huge difference."^[6] Depp explained that the similarities with Jackson never occurred to him. "I say if there was anyone you'd want to compare Wonka to it would be a Howard Hughes, almost. Reclusive, germaphobe, controlling."^[9] Burton agreed with the Hughes similarities, and additionally supplied Charles Foster Kane in Citizen Kane as inspiration. "Somebody who was brilliant but then was traumatized and then retreats into their own world."^[7] Depp wanted to sport prosthetic makeup for the part and have a long, elongated nose, but Burton believed it would be too outrageous.^[5]

Critical analysis[link]

Wilder's performance as Willy Wonka was well received and remains one of his best-known roles. Time Out Film Guide called it "Great fun, with Wilder for once giving an impeccably controlled performance as the factory's bizarre candy owner."^[10] Critic Jeffrey M. Anderson, of Combustible Celluloid, wrote "...when the movie does actually reach the factory, and Gene Wilder takes the stage, the movie is saved. Wilder was in the middle of an incredible run of subtle comic performances... and he was at the height of his powers here."^[11] Regarding Wilder's effect, Anderson wrote "If you're a kid, Wonka seems magical, but watching it now, he has a frightening combination of warmth, psychosis, and sadism."^[12] Kevin Carr, of 7M pictures wrote "This is Gene Wilder's legacy. He was perfect for the role, and it was his mixture of childlike wonder and bitter, deserved vengeance that made the character so compelling."^[13], while critic Widgett Walls simply called it "Probably Gene Wilder's finest, most manic hour." ^[14] Wilder received a nomination for the Golden Globe Award for Best Actor in a Musical or Comedy for his role as Willy Wonka, but lost to Chaim Topol as Tevye in Fiddler on the Roof.^[15]

Critical response to Johnny Depp's performance as Willy Wonka was often enthusiastic but more mixed overall. Critic Andrew Sarris, of The New York Observer, who did not enjoy the film's style in general, wrote "I wonder if even children will respond to the peculiarly humorless and charmless stylistic eccentricities of Mr. Burton and his star, Johnny Depp."^[16] However, Owen Gleiberman of Entertainment Weekly wrote that "Johnny Depp as Willy Wonka may be a stone freak, but he is also one of Burton's classic crackpot conjurers, like Beetlejuice or Ed Wood."^[17] Mick LaSalle from the San Francisco Chronicle found that "all the laughs [in the film] come from Depp, who gives Willy the mannerisms of a classic Hollywood diva".^[18] Roger Ebert wrote "Depp, an actor of considerable gifts, has never been afraid to take a chance, but this time he takes the wrong one. His Willy Wonka is an enigma in an otherwise mostly delightful movie from Tim Burton,"^[19] while Peter Travers wrote in Rolling Stone magazine that "Depp's deliciously demented take on Willy Wonka demands to be seen. Depp goes deeper to find the bruises on Wonka's secret heart than what Gene Wilder did."^[20] Ann Hornaday of The Washington Post also criticized Depp's acting; "The cumulative effect isn't pretty. Nor is it kooky, funny, eccentric or even mildly interesting. Indeed, throughout his fey, simpering performance, Depp seems to be straining so hard for weirdness that the entire enterprise begins to feel like those excruciating occasions when your parents tried to be hip."^[21] Joe Lozito of Big Picture Big Sound questioned the intention as well, writing "Depp's Wonka exudes none of the gravity required for the role. It's as though he didn't take the role seriously. Rather than an intimidating candyman teaching brats a lesson, this Wonka is simply a freak."^[22] Depp received a nomination for the Golden Globe Award for Best Actor in a Musical or Comedy for his role as Willy Wonka, but lost to Joaquin Phoenix as Johnny Cash in Walk the Line.^[23]

References[link]