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

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Gene Pitney
Pitney in 1967.
Background information
Birth name	Gene Francis Alan Pitney
Also known as	Billy Bryan
Born	(1941-02-17)February 17, 1941 Hartford, Connecticut, United States
Origin	Rockville, Connecticut, United States
Died	April 5, 2006(2006-04-05) (aged 65) Cardiff, Wales, UK
Genres	Rock and roll
Occupations	Singer, songwriter, musician
Instruments	Guitar, piano, drums
Years active	1961–2006

Gene Francis Alan Pitney (February 17, 1941 – April 5, 2006) was an American singer-songwriter, musician, and sound engineer. Through the mid-1960s, he enjoyed success as a recording artist on both sides of the Atlantic and was among the group of early 1960s American acts who continued to enjoy hits after the British Invasion. Pitney charted 16 Top-40 hits in the U.S., four in the Top 10. In the UK he had 22 Top-40 hits, and 11 singles in the Top Ten. He also wrote the early 1960s hits "Rubber Ball" by Bobby Vee, "He's a Rebel" by The Crystals, and "Hello Mary Lou" by Rick Nelson. In 2002, he was inducted into the Rock and Roll Hall of Fame.

Early years[link]

Pitney was born in Hartford, Connecticut, and grew up in Rockville, now part of Vernon, Connecticut. His early influences were Clyde McPhatter, country-blues singer Moon Mullican and doo-wop groups like The Crows. He attended Rockville High School, at which he was named "the Rockville Rocket", and where he formed his first band, Gene & the Genials. He made records as part of a duo called Jamie and Jane with Ginny Arnell (who in late 1963 had a solo hit, "Dumb Head"), and in 1959 recorded a single as Billy Bryan. The first of the two Decca 45s as Jamie and Jane was "Snuggle Up, Baby," a cover of a song Charlie Gracie recorded at Cameo 1957 or early 1958, which remained unreleased until London Records released Gracie's original version in Europe in 1978.

Career[link]

Rise to fame (1961–1964)[link]

Signed to songwriter Aaron Schroeder's newly formed Musicor label in 1961, Pitney scored his first chart single, which made the Top 40, the self-penned "(I Wanna) Love My Life Away", on which he played several instruments and multi-tracked the vocals. He followed that same year with his first Top 20 single, the title song from the film Town Without Pity starring Kirk Douglas. Written by Dimitri Tiomkin and Ned Washington, the song won a Golden Globe Award and was nominated for an Academy Award for Best Song. Pitney performed the song at the Oscars ceremony on 9 April 1962 (honoring the film year of 1961). The song lost the Academy Award to "Moon River". "Town Without Pity" would be the last song Gene Pitney would sing in public, at a gig in south Wales before his death at the age of 65.

Pitney is also remembered for Burt Bacharach-Hal David song "The Man Who Shot Liberty Valance", which peaked at No. 4 in 1962. Though it shares a title with a 1962 John Ford western with the same title, The Man Who Shot Liberty Valance, starring John Wayne, the song was not used in the film because of a publishing dispute between Famous Music and Paramount Pictures.

Meanwhile, Pitney wrote hits for others, including "He's a Rebel" for The Crystals, Vikki Carr, and Elkie Brooks; "Today's Teardrops" for Roy Orbison; "Rubber Ball" for Bobby Vee; and "Hello Mary Lou" for Ricky Nelson. "He's A Rebel" kept Pitney's own #2 hit Only Love Can Break a Heart, his highest-charting single in the U.S., from the top spot.

Pitney's 1963 hit "Mecca" can be regarded^{[weasel words]} as a precursor to psychedelia in its use of Arabian music several years before The Beatles began experimenting with exotic sounds. Exotic instruments became a Pitney trademark, such as mariachi trumpets in "Lonely Drifter", ukuleles in "Hawaii", and a gypsy fiddle in "Golden Earrings".

His popularity in the UK market was ensured by the breakthrough success of "Twenty Four Hours from Tulsa", a Bacharach and David song, which peaked at No.5 in Britain at the start of 1964 ("Twenty-Four Hours From Tulsa" was only Pitney's third single release in the UK to reach the singles chart and the first to break the Top Twenty there). "Twenty-Four Hours From Tulsa" was also a hit in the U.S, peaking at No.17 on the US Billboard Hot 100.

Involvement with the Rolling Stones (1964)[link]

Pitney was present with Phil Spector at some of the Rolling Stones' early recording sessions in London, including "Little by Little" and other tracks for their debut album;^[1] he played piano, though the extent is uncertain.

The Jagger/Richards song "That Girl Belongs to Yesterday" was a UK hit for Pitney in 1964; it was the first tune composed by the Rolling Stones to become a Top 10 hit in the UK.^[2] In the U.S. the single stalled at No. 49, ending a run of seven Top 40 singles for Pitney as a performer.

Maintaining popularity[link]

After another low-charting single, 1964's "Yesterday's Hero", Pitney rebounded with another string of hits in the mid-1960s, including the 1964 singles "It Hurts to Be in Love" (previously mentioned) and "I'm Gonna Be Strong", which reached No. 7 and No. 9, respectively, in the U.S., and 1966's "Nobody Needs Your Love", which peaked at No. 2 in the UK. ("I'm Gonna Be Strong" also reached No. 2 on the UK charts.) "It Hurts to Be in Love" had been planned for and recorded by Neil Sedaka, but RCA refused to release it because Sedaka had recorded the song outside RCA Victor in violation of his contract. The writers, Howard Greenfield and Helen Miller, presented the song to Pitney. Miller replaced Sedaka's voice with Pitney's, though Sedaka's trademark backing harmonies were left intact.

In 1965, Pitney recorded two successful albums with country singer George Jones. They were voted the most promising country-and-western duo of the year. Pitney also recorded songs in Italian, Spanish and German, and twice finished second in Italy's annual Sanremo Music Festival, where his strong vibrato reminded older listeners of the Italian tenor Caruso. He had a regional hit with "Nessuno Mi Puo' Giudicare".

UK, Australian and European stardom (1966–1970s)[link]

Pitney's career in the U.S. took a downturn after mid-1966, when "Backstage" ended another run of Top 40 hits. He returned one last time to the Top 40 with "She's a Heartbreaker" in mid-1968 and placed several singles in the lower reaches of the Hot 100 after that, but by 1970 he was no longer a hit-maker in the U.S.

Pitney maintained a successful career in Britain and the rest of Europe into the 1970s, appearing regularly on UK charts as late as 1974. In Australia, after a fallow period in the early 1970s, Pitney returned to Top 40 in 1974, as both Blue Angel (No. 2) and Trans-Canada Highway (No. 14; production by David Mackay) were substantial hits. Pitney continued to place records in the Australian charts through 1976, including the hit "Down This Road", written and produced by distant relation Edward Pitney. They also collaborated in the production of the hit song "Days of Summer".

In the early 1970s, Pitney decided to spend only six months each year on the road.

Later career[link]

Pitney's last hit on the UK charts came in 1989, after an absence of 15 years, when he and Soft Cell singer Marc Almond recorded a duet version of "Something's Gotten Hold of My Heart" by British writers Roger Cook and Roger Greenaway. The song had been a UK No. 5 for Pitney in 1967. The duet brought him his first UK No. 1, in late January 1989. The single remained at the top for four weeks, and also went to No. 1 elsewhere in Europe. Pitney and Almond appeared on the Terry Wogan television show in Britain, Almond dressed in leather, Pitney in a white tuxedo.

Nick Cave and the Bad Seeds had recorded "Something's Gotten Hold of My Heart" on their cover album, Kicking Against the Pricks, in 1986. However, it never had the success of Pitney-Almond.

On 26 February 1993, Pitney performed at Carnegie Hall in New York on the day of the first World Trade Center bombing. On 18 March 2002 he was inducted into the Rock and Roll Hall of Fame.

Death[link]

Pitney died on April 5, 2006, aged 65. His tour manager found him dead in the Hilton Hotel, in Cardiff, Wales, in the middle of a UK tour.^[3] His final show at Cardiff's St. David's Hall earned him a standing ovation; he ended with "Town Without Pity". An autopsy confirmed that he had a heart disease, caused by atherosclerosis. He left a wife, Lynne, and three sons, Todd, Chris, and David.^[4] He was buried at Somers Center Cemetery in Somers, Connecticut.

Posthumous tributes[link]

Marc Almond recorded "Backstage (I'm Lonely)" for his 2007 covers album, Stardom Road.

On 20 September 2007, a plaque to Pitney was unveiled at the town hall in his hometown of Rockville, Connecticut. Members of the family attended. The event was emceed by nationally known oldies radio DJ and Pitney friend "Wild" Wayne. The Gene Pitney Commemorative Committee established a music scholarship in Pitney's name. It is awarded annually to Rockville High School. In October 2008, an international fan convention was held in Rockville. In 2009, Pitney was inducted into the Hit Parade Hall of Fame.

Discography[link]

Singles[link]

Note that release dates refer to initial release. Pitney's early singles generally appeared one to four months later in the UK/Australia. Many of his later releases are UK/Australia/NZ only.

Sources include Joel Whitburn's Record Research material for the U.S. Top 100, "Bubbling Under" and U.S. Country charts; Tim Rice et al., Guinness Book of Hit Singles for the UK; CHUM Chart for Canada prior to mid-1964, and the Canadian RPM charts thereafter; and The Kent Report for Australia

References[link]

External links[link]

• Gene Pitney bio
• A site created to honor Gene in his hometown of Rockville, CT
• "Wild" Wayne - Ct. based nationally known Oldies Radio DJ & friend of Gene Pitney
• Rock and Roll Hall of Fame
• Report of Pitney's death from BBC News
• BBC Obituary
• Obituary from The Guardian
• Fan's Final Chat with Gene Pitney
• Interview with Gene Pitney in International Songwriters Association's "Songwriter Magazine", concentrating on his songwriting career

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2012)

"The Man" is a slang phrase that may refer to the government or to some other authority in a position of power. In addition to this derogatory connotation, it may also serve as a term of respect and praise.

The phrase "the Man is keeping me down" is commonly used to describe oppression. The phrase "stick it to the Man" encourages resistance to authority, and essentially means "fight back" or "resist", either openly or via sabotage.^[1]

History[link]

The earliest recorded use^{[citation needed]} of the term "the Man" in the American sense dates back to a letter written by a young Alexander Hamilton in September 1772, when he was 15. In a letter to his father James Hamilton, published in the Royal Dutch-American Gazette, he described the response of the Dutch governor of St. Croix to a hurricane that raked that island on August 31, 1772. "Our General has issued several very salutary and humane regulations and both in his publick and private measures, has shewn himself the Man." ^{[2][dubious – discuss]} In the Southern U.S. states, the phrase came to be applied to any man or any group in a position of authority, or to authority in the abstract. From about the 1950s the phrase was also an underworld code word for police, the warden of a prison or other law enforcement or penal authorities.

It was also used as a term for a drug dealer in the 1950s and 1960s and can be seen in such media as Curtis Mayfield's "No Thing On Me", William Burroughs's novel Naked Lunch, and in the Velvet Underground song "I'm Waiting for the Man", in which Lou Reed sings about going to Uptown Manhattan, specifically Lexington Avenue and 125th Street, to buy heroin.

The use of this term was expanded to counterculture groups and their battles against authority, such as the Yippies, which, according to a May 19, 1969 article in U.S. News and World Report, had the "avowed aim ... to destroy 'The Man', their term for the present system of government". The term eventually found its way into humorous usage, such as in a December 1979 motorcycle ad from the magazine Easyriders which featured the tagline, "California residents: Add 6% sales tax for The Man."

In present day, the phrase has been popularized in commercials and cinema, featuring particularly prominently as a recurring motif in the 2003 film School of Rock.^[3][4][5][6]

Use as praise[link]

The term has also been used as an approbation or form of praise. This may refer to the recipient's status as the leader or authority within a particular context, or it might be assumed to be a shortened form of a phrase like "He is the man (who is in charge)." One example of this usage dates to 1879 when Otto von Bismarck commented, referring to Benjamin Disraeli's pre-eminent position at the Congress of Berlin, "The old Jew, he is the man."^{[7][dubious – discuss]}

In more modern usage, it can be a superlative compliment ("you da man!") indicating that the subject is currently standing out amongst his peers even though they have no special designation or rank, such as a basketball player who is performing better than the other players on the court. It can also be used as a genuine compliment with an implied, slightly exaggerated or sarcastic tone, usually indicating that the person has indeed impressed the speaker but by doing something relatively trivial.

See also[link]

• Absentee landlord
• Big Brother (Nineteen Eighty-Four)
• New World Order (conspiracy theory)
• Ruling class
• The Establishment
• Power elite
• Corrections officer
• YTMND

Notes[link]

References[link]

• Lighter, J.E. (Ed.). (1997). Random House Dictionary of American Slang. New York: Random House.

For people named Jean Kelly, see Jean Kelly (disambiguation).

Gene Kelly
Gene Kelly in 1943
Born	Eugene Curran Kelly (1912-08-23)August 23, 1912 Pittsburgh, Pennsylvania
Died	February 2, 1996(1996-02-02) (aged 83) Beverly Hills, California
Occupation	Actor, dancer, singer, director, producer, choreographer
Years active	1938–1994
Spouse	Betsy Blair (m.1941-1957; divorced) Jeanne Coyne (m.1960-1973; her death) Patricia Ward (m.1990-1996; his death)

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

Although he is known today for his performances in Singin' in the Rain and An American in Paris, he was a dominant force in Hollywood musical films from the mid 1940s until this art form fell out of fashion in the late 1950s. His many innovations transformed the Hollywood musical film, and he is credited with almost single-handedly making the ballet form commercially acceptable to film audiences.^[1]

Kelly was the recipient of an Academy Honorary Award in 1952 for his career achievements. He later received lifetime achievement awards in the Kennedy Center Honors, and from the Screen Actors Guild and American Film Institute; in 1999, the American Film Institute also numbered him 15th in their Greatest Male Stars of All Time list.

Early life[link]

Kelly's senior picture from the 1933 yearbook of the University of Pittsburgh

Kelly was born in the Highland Park neighborhood of Pittsburgh. He was the third son of Harriet Catherine (née Curran) and James Patrick Joseph Kelly, a phonograph salesman.^[2] His father was born in Peterborough, Canada, to a family of Irish descent. His maternal grandfather was an immigrant from Derry in northern Ireland and his maternal grandmother was of German ancestry.^[3] At the age of eight, Kelly was enrolled by his mother in dance classes, along with his elder brother James. They both rebelled, and, according to Kelly: "We didn't like it much and were continually involved in fistfights with the neighborhood boys who called us sissies...I didn't dance again until I was fifteen." He thought it would be a good way to get girls.^[4] Kelly returned to dance on his own initiative and by then was an accomplished sportsman and well able to take care of himself. He attended St. Raphael Elementary School ^[5] in the Morningside neighborhood of Pittsburgh, PA. He graduated from Peabody High School in 1929 at the age of sixteen. He enrolled in Pennsylvania State College to study journalism but the economic crash obliged him to seek employment to help with the family's finances. At this time, he worked up dance routines with his younger brother Fred in order to earn prize money in local talent contests, and they also performed in local nightclubs.^[4]

In 1931, Kelly enrolled at the University of Pittsburgh to study economics where he joined the Phi Kappa Theta fraternity.^[6] While at Pitt, Kelly became involved in the university's Cap and Gown Club, which staged original, comedic musical productions.^[7] Earning a Bachelor of Arts in Economics with his graduation from Pitt in 1933, he remained active with the Cap and Gown Club, serving as its director from 1934 to 1938, while at the same time enrolling in the University of Pittsburgh Law School.^[8] Also during this period, Kelly's family started a dance studio on Munhall Road in the Squirrel Hill neighborhood of Pittsburgh. In 1932, the dance studio was renamed The Gene Kelly Studio of the Dance. A second location was opened in Johnstown, Pennsylvania in 1933. Kelly served as a teacher at the studio during both his undergraduate and law student years at Pitt. In 1931, he was approached by the Rodef Shalom synagogue in Pittsburgh to teach dance, and to stage the annual Kermess. This venture was successful enough that his services were retained for seven years until his departure for New York.^[9] Eventually, though, he decided to pursue his career as a dance teacher and full-time entertainer, so Kelly dropped out of law school after two months. He began to increasingly focus on performing and later claimed: "With time I became disenchanted with teaching because the ratio of girls to boys was more than ten to one, and once the girls reached sixteen the dropout rate was very high."^[4] In 1937, having successfully managed and developed the family's dance school business, he finally did move to New York City in search of work as a choreographer.^[4]

Stage career[link]

After a fruitless search, Kelly returned to Pittsburgh, to his first position as a choreographer with the Charles Gaynor musical revue Hold Your Hats at the Pittsburgh Playhouse in April, 1938. Kelly appeared in six of the sketches, one of which, "La Cumparsita", became the basis of an extended Spanish number in Anchors Aweigh" eight years later.

His first Broadway assignment, in November 1938, was as a dancer in Cole Porter's Leave It to Me! as the American ambassador's secretary who supports Mary Martin while she sings "My Heart Belongs to Daddy". He had been hired by Robert Alton who had staged a show at the Pittsburgh Playhouse and been impressed by Kelly's teaching skills. When Alton moved on to choreograph One for the Money he hired Kelly to act, sing and dance in a total of eight routines. In 1939, he was selected to be part of a musical revue "One for the Money" produced by the actress Katharine Cornell, who was known for finding and hiring talented young actors.

Kelly's first career breakthrough was in the Pulitzer Prize-winning The Time of Your Life, which opened on October 25, 1939, where for the first time on Broadway he danced to his own choreography. In the same year he received his first assignment as a Broadway choreographer, for Billy Rose's Diamond Horseshoe. His future wife, Betsy Blair, was a member of the cast. They began dating and married on October 16, 1941.

In 1940, he was given the leading role in Rodgers and Hart's Pal Joey, again choreographed by Robert Alton, and this role propelled him to stardom. During its run he told reporters: "I don't believe in conformity to any school of dancing. I create what the drama and the music demand. While I am a hundred percent for ballet technique, I use only what I can adapt to my own use. I never let technique get in the way of mood or continuity."^[4] It was at this time also, that his phenomenal commitment to rehearsal and hard work was noticed by his colleagues. Van Johnson who also appeared in Pal Joey recalled: "I watched him rehearsing, and it seemed to me that there was no possible room for improvement. Yet he wasn't satisfied. It was midnight and we had been rehearsing since eight in the morning. I was making my way sleepily down the long flight of stairs when I heard staccato steps coming from the stage...I could see just a single lamp burning. Under it, a figure was dancing...Gene."^[4]

Offers from Hollywood began to arrive but Kelly was in no particular hurry to leave New York. Eventually, he signed with David O. Selznick, agreeing to go to Hollywood at the end of his commitment to Pal Joey, in October 1941. Prior to his contract, he also managed to fit in choreographing the stage production of Best Foot Forward.

Film career[link]

1941–1944: Becoming established in Hollywood[link]

Selznick sold half of Kelly's contract to MGM and loaned him out to MGM for his first motion picture: For Me and My Gal (1942) with Judy Garland. Kelly was "appalled at the sight of myself blown up twenty times. I had an awful feeling that I was a tremendous flop" but the picture did well and, in the face of much internal resistance, Arthur Freed of MGM picked up the other half of Kelly's contract.^[4] After appearing in the B-movie drama Pilot #5 he took the male lead in Cole Porter's Du Barry Was a Lady opposite Lucille Ball. His first opportunity to dance to his own choreography came in his next picture Thousands Cheer, where he performed a mock-love dance with a mop.

He achieved his breakthrough as a dancer on film when MGM loaned him out to Columbia to work with Rita Hayworth in Cover Girl (1944), where he created a memorable routine dancing to his own reflection. In his next film Anchors Aweigh (1945), MGM virtually gave him a free hand to devise a range of dance routines, including the celebrated and much imitated animated dances with Jerry Mouse, and his duets with co-star Frank Sinatra.^[10] Anchors Aweigh became one of the most successful films of 1945 and it garnered Kelly his first and only Academy Award nomination for Best Actor. In Ziegfeld Follies (1946) – which was produced in 1944 but not released until 1946 – Kelly collaborated with Fred Astaire – for whom he had the greatest admiration – in the famous "The Babbitt and the Bromide" challenge dance routine.

At the end of 1944, Kelly enlisted in the U.S. Naval Air Service and was commissioned as lieutenant junior grade. He was stationed in the Photographic Section, Washington D.C., where he was involved in writing and directing a range of documentaries, and this stimulated his interest in the production side of film-making.^[6][11]

1946–1952: MGM[link]

On his return to Hollywood in the spring of 1946, MGM had nothing lined up and used him in yet another B-movie: Living in a Big Way. The film was considered so weak that Kelly was asked to design and insert a series of dance routines, and his ability to carry off such assignments was noticed. This led to his next picture with Judy Garland and director Vincente Minnelli, the film version of Cole Porter's The Pirate, in which Kelly plays the eponymous swashbuckler. Now regarded as a classic, the film was ahead of its time and was not well received. The Pirate gave full rein to Kelly's athleticism and is probably best remembered for Kelly's work with The Nicholas Brothers – the leading African-American dancers of their day – in a virtuoso dance routine.

Take Me Out to the Ballgame (1949)

Although MGM wanted Kelly to return to safer and more commercial vehicles, he ceaselessly fought for an opportunity to direct his own musical film. In the interim, he capitalised on his swashbuckling image as d'Artagnan in The Three Musketeers. and also appeared with Vera-Ellen in the Slaughter on Tenth Avenue ballet in Words and Music (1948). He was due to play the male lead opposite Garland in Easter Parade (1948), but broke his ankle playing volleyball. He withdrew from the film and encouraged Fred Astaire to come out of retirement to replace him.^[12] There followed Take Me Out to the Ball Game (1949), his second film with Sinatra, where Kelly paid tribute to his Irish heritage in The Hat My Father Wore on St. Patrick's Day routine. It was this musical film which persuaded Arthur Freed to allow Kelly to make On the Town, where he partnered with Frank Sinatra for the third and final time, creating a breakthrough in the musical film genre which has been described as "the most inventive and effervescent musical thus far produced in Hollywood."^[4]

Stanley Donen, brought to Hollywood by Kelly to be his assistant choreographer, received co-director credit for On the Town. According to Kelly: "...when you are involved in doing choreography for film you must have expert assistants. I needed one to watch my performance, and one to work with the cameraman on the timing..without such people as Stanley, Carol Haney and Jeanne Coyne I could never have done these things. When we came to do On the Town, I knew it was time for Stanley to get screen credit because we weren't boss-assistant anymore but co-creators."^[4][13] Together, they opened up the musical form, taking the film musical out of the studio and into real locations, with Donen taking responsibility for the staging and Kelly handling the choreography. Kelly went much further than before in introducing modern ballet into his dance sequences, going so far in the "Day in New York" routine as to substitute four leading ballet specialists for Sinatra, Munshin, Garrett and Miller.^[6]

It was now Kelly's turn to ask the studio for a straight acting role and he took the lead role in the early mafia melodrama: The Black Hand (1949). This expose of organized crime is set in New York's "Little Italy" the late 19th century, and focuses on the Black Hand, a group which extorts money upon threat of death. In the real-life incidents upon which this film is based, it was the Mafia, not the Black Hand, who functioned as the villain. Even in 1950, however, Hollywood had to tread gingerly whenever dealing with big-time crime; it was easier (and safer) to go after a "dead" criminal organization than a "live" one.

There followed Summer Stock (1950) – Judy Garland's last musical film for MGM – in which Kelly performed the celebrated "You, You Wonderful You" solo routine with a newspaper and a squeaky floorboard. In his book "Easy the Hard Way", Joe Pasternak, head of one of the other musical units within MGM, singled out Kelly for his patience and willingness to spend as much time as necessary to enable the ailing Garland to complete her part.^[4]

There followed in quick succession two musicals which have secured Kelly's reputation as a major figure in the American musical film, An American in Paris (1951) and – probably the most popular and admired of all film musicals – Singin' in the Rain (1952). As co-director, lead star and choreographer, Kelly was the central driving force. Johnny Green, head of music at MGM at the time, described him as follows:

"Gene is easygoing as long as you know exactly what you are doing when you're working with him. He's a hard taskmaster and he loves hard work. If you want to play on his team you'd better like hard work, too. He isn't cruel but he is tough, and if Gene believed in something he didn't care who he was talking to, whether it was Louis B. Mayer or the gatekeeper. He wasn't awed by anybody, and he had a good record of getting what he wanted".^[4]

An American in Paris won six Academy Awards, including Best Picture and, in the same year, Kelly was presented with an honorary Academy Award for his contribution to film musicals and the art of choreography. The film also marked the debut of Leslie Caron, whom Kelly had spotted in Paris and brought to Hollywood. Its dream ballet sequence, lasting an unprecedented seventeen minutes, was the most expensive production number ever filmed up to that point and was described by Bosley Crowther as, "whoop-de-doo ... one of the finest ever put on the screen."^[6] Singin' in the Rain featured Kelly's celebrated and much imitated solo dance routine to the title song, along with the "Moses Supposes" routine with Donald O'Connor and the "Broadway Melody" finale with Cyd Charisse, and while it did not initially generate the same enthusiasm as An American in Paris, it subsequently overtook the earlier film to occupy its current pre-eminent place among critics and filmgoers alike.^[14]

1953–57: The Decline of the Hollywood Musical[link]

Kelly, at the very peak of his creative powers, now made what in retrospect is seen as a serious mistake.^[6] In December 1951 he signed a contract with MGM which sent him to Europe for nineteen months so that Kelly could use MGM funds frozen in Europe to make three pictures while personally benefiting from tax exemptions. Only one of these pictures was a musical, Invitation to the Dance, a pet project of Kelly's to bring modern ballet to mainstream film audiences. It was beset with delays and technical problems, and flopped when finally released in 1956. When Kelly returned to Hollywood in 1953, the film musical was already beginning to feel the pressures from television, and MGM cut the budget for his next picture Brigadoon (1954), with Cyd Charisse, forcing the film to be made on studio backlots instead of on location in Scotland. This year also saw him appear as guest star with his brother Fred in the celebrated "I Love to Go Swimmin' with Wimmen" routine in Deep in My Heart. MGM's refusal to loan him out for Guys and Dolls and Pal Joey put further strains on his relationship with the studio. He negotiated an exit to his contract which involved making three further pictures for MGM.

The first of these, It's Always Fair Weather (1956) co-directed with Donen, was a musical satire on television and advertising, and includes his famous roller skate dance routine to "I Like Myself", and a dance trio with Michael Kidd and Dan Dailey which allowed Kelly to experiment with the widescreen possibilities of Cinemascope. A modest success, it was followed by Kelly's last musical film for MGM, Les Girls (1957), in which he partnered a trio of leading ladies, Mitzi Gaynor, Kay Kendall and Taina Elg, fittingly ending, as he had begun, with a Cole Porter musical. The third picture he completed was a co-production between MGM and himself, the B-movie The Happy Road, set in his beloved France, his first foray in his new role as producer-director-actor.

1958–1996: Years of perseverance[link]

Leaving MGM in 1957, Kelly returned to stage work. When in 1958 he directed Rodgers and Hammerstein's musical play Flower Drum Song.^[15] Early in 1960, Kelly, an ardent Francophile and fluent French speaker, was invited by A. M. Julien, the general administrator of the Paris Opéra and Opéra-Comique,^[4] to select his own material and create a modern ballet for the company, the first time an American had received such an assignment. The result was Pas de Dieux, based on Greek mythology, combined with the music of George Gershwin's Concerto in F. It was a major success, and led to his being honoured with the Chevalier of the Legion d'Honneur by the French Government.

Kelly as Hornbeck in Inherit the Wind

Kelly continued to make some film appearances, such as Hornbeck in the 1960 Hollywood production of Inherit the Wind. However, most of his efforts were now concentrated on film production and directing. In 1962, he directed Jackie Gleason in Gigot in Paris, but the film was drastically re-cut by Seven Arts Productions and flopped.^[6] Another French effort, Jacques Demy's homage to the MGM musical: Les Demoiselles de Rochefort (1967) in which Kelly appeared, was popular in France and nominated for Academy Awards for Best Music and Score of a Musical Picture (Original or Adaptation) but performed poorly, elsewhere. He appeared as himself in George Cukor's Let's Make Love (1960).

His first foray into television was a documentary for NBC's Omnibus, Dancing is a Man's Game (1958) where he assembled a group of America's greatest sportsmen – including Mickey Mantle, Sugar Ray Robinson and Bob Cousy – and re-interpreted their moves choreographically, as part of his lifelong quest to remove the effeminate stereotype of the art of dance, while articulating the philosophy behind his dance style.^[6] It gained an Emmy nomination for choreography and now stands as the key document explaining Kelly's approach to modern dance.

Kelly also frequently appeared on television shows during the 1960s, but his one effort at television series, as Father Chuck O'Malley in Going My Way (1962–63), based on the Best Picture of 1944 starring Bing Crosby, was dropped after thirty episodes, although it enjoyed great popularity in Roman Catholic countries outside of the United States.^[6] He also appeared in three major TV specials: New York, New York (1966), The Julie Andrews' Show (1965), and Jack and the Beanstalk (1967) a show he produced and directed which returned to a combination of cartoon animation with live dance, winning him an Emmy Award for Outstanding Children's Program.

In 1963, Kelly joined Universal Pictures for a two-year stint, which proved to be the most unproductive period of his career at that point. He joined 20th Century Fox in 1965, but had little to do – partly due to his decision to decline assignments away from Los Angeles for family reasons. His perseverance finally paid off, with the major box-office hit A Guide for the Married Man (1967) where he directed Walter Matthau. Then, a major opportunity arose when Fox – buoyed by the returns from The Sound of Music (1965) – commissioned Kelly to direct Hello, Dolly! (1969), again directing Matthau along with Barbra Streisand, but which unfortunately failed to recoup the enormous production expenses.

In 1970, he made another TV special: Gene Kelly and 50 Girls and was invited to bring the show to Las Vegas, Nevada, which he duly did for an eight-week stint – on condition he be paid more than any artist had hitherto been paid there.^[6] He directed veteran actors James Stewart and Henry Fonda in the comedy western The Cheyenne Social Club (1970) which performed very well at the box-office. In 1973, he would work again with Frank Sinatra as part of Sinatra's Emmy nominated TV special Ol' Blue Eyes Is Back. Then, in 1974, he appeared as one of many special narrators in the surprise hit of the year That's Entertainment! and subsequently directed and co-starred with his friend Fred Astaire in the sequel That's Entertainment, Part II (1976). It was a measure of his powers of persuasion that he managed to coax the 77-year-old Astaire – who had insisted that his contract rule out any dancing, having long since retired – into performing a series of song and dance duets, evoking a powerful nostalgia for the glory days of the American musical film. Kelly continued to make frequent TV appearances and, in 1980, appeared in an acting and dancing role opposite Olivia Newton-John in Xanadu (1980), an expensive theatrical flop which has since attained a cult following.^[6] In Kelly's opinion, "The concept was marvelous but it just didn't come off."^[4] In the same year, he was invited by Francis Ford Coppola to recruit a production staff for American Zoetrope's One from the Heart (1982). Although Coppola's ambition was for him to establish a production unit to rival the Freed Unit at MGM, the film's failure put an end to this idea.^[6] In 1985, Kelly served as executive producer and co-host of That's Dancing! – a celebration of the history of dance in the American musical. After his final on-screen appearance, introducing That's Entertainment! III, in 1994, his final film project was the animated movie Cats Don't Dance, released in 1997 and dedicated to him, on which Kelly acted as uncredited choreographic consultant.

Working methods and influence on filmed dance[link]

When he began his collaborative film work, he was influenced by Robert Alton and John Murray Anderson, striving to create moods and character insight with his dances. He choreographed his own movement, along with that of the ensemble, with the assistance of Jeanne Coyne, Stanley Donen, Carol Haney, and Alex Romero.^[1] He experimented with lighting, camera techniques and special effects in order to achieve true integration of dance with film, and was one of the first to use split screens, double images, live action with animation and is credited as the person who made the ballet form commercially acceptable to film audiences.^[1]

There was a clear progression in his development, from an early concentration on tap and musical comedy style to greater complexity using ballet and modern dance forms.^[16] Kelly himself refused to categorize his style: "I don't have a name for my style of dancing...It's certainly hybrid...I've borrowed from the modern dance, from the classical, and certainly from the American folk dance – tap-dancing, jitterbugging...But I have tried to develop a style which is indigenous to the environment in which I was reared."^[16] He especially acknowledged the influence of George M. Cohan: "I have a lot of Cohan in me. It's an Irish quality, a jaw-jutting, up-on-the-toes cockiness – which is a good quality for a male dancer to have."^[4] He was also heavily influenced by an African-American dancer Dancing Dotson, whom he saw at Loew's Penn. Theatre around 1929, and was briefly taught by Frank Harrington, an African-American tap specialist from New York.^[17] However, his main interest was in ballet, which he studied under Kotchetovsky in the early Thirties. As biographer Clive Hirschhorn explains: "As a child he used to run for miles through parks and streets and woods – anywhere, just as long as he could feel the wind against his body and through his hair. Ballet gave him the same feeling of exhilaration, and in 1933 he was convinced it was the most satisfying form of self-expression."^[6] He also studied Spanish dancing under Angel Cansino, Rita Hayworth's uncle.^[6] Generally speaking, he tended to use tap and other popular dance idioms to express joy and exuberance – as in the title song from Singin' in the Rain or "I Got Rhythm" from An American in Paris, whereas pensive or romantic feelings were more often expressed via ballet or modern dance, as in "Heather on the Hill" from Brigadoon or "Our Love Is Here to Stay" from An American in Paris.^[16]

According to Delamater, Kelly's work "seems to represent the fulfillment of dance-film integration in the 1940s and 1950s". While Fred Astaire had revolutionized the filming of dance in the 1930s by insisting on full-figure photography of dancers while allowing only a modest degree of camera movement, Kelly freed up the camera, making greater use of space, camera movement, camera angles and editing, creating a partnership between dance movement and camera movement without sacrificing full-figure framing. Kelly's reasoning behind this was that he felt the kinetic force of live dance often evaporated when brought to film, and he sought to partially overcome this by involving the camera in movement and giving the dancer a greater number of directions in which to move. Examples of this abound in Kelly's work and are well illustrated in the "Prehistoric Man" sequence from On the Town and "The Hat My Father Wore on St. Patrick's Day" from Take Me Out to the Ball Game.^[16] In 1951, he summed up his vision as follows: "If the camera is to make a contribution at all to dance, this must be the focal point of its contribution; the fluid background, giving each spectator an undistorted and altogether similar view of dancer and background. To accomplish this, the camera is made fluid, moving with the dancer, so that the lens becomes the eye of the spectator, your eye".^[1]

Kelly's athleticism gave his moves a distinctive broad, muscular quality,^[16] and this was a very deliberate choice on his part, as he explained: "There's a strong link between sports and dancing, and my own dancing springs from my early days as an athlete...I think dancing is a man's game and if he does it well he does it better than a woman."^[4] He railed against what he saw as the widespread effeminacy in male dancing which, in his opinion, "tragically" stigmatized the genre, alienating boys from entering the field: "Dancing does attract effeminate young men. I don't object to that as long as they don't dance effeminately. I just say that if a man dances effeminately he dances badly — just as if a woman comes out on stage and starts to sing bass. Unfortunately people confuse gracefulness with softness. John Wayne is a graceful man and so are some of the great ball players...but, of course, they don't run the risk of being called sissies."^[4] In his view, "one of our problems is that so much dancing is taught by women. You can spot many male dancers who have this tuition by their arm movements — they are soft, limp and feminine."^[4] He acknowledged that, in spite of his efforts — in TV programs such as Dancing: A Man's Game (1958) for example — the situation changed little over the years.^[4]

He also sought to break from the class-conscious conventions of the 1930s and early 40s, when top hat and tails or tuxedos were the norm, by dancing in casual or everyday work clothes, so as to make his dancing more relevant to the cinema-going public. As his first wife, actress and dancer Betsy Blair explained: "A sailor suit or his white socks and loafers, or the T-shirts on his muscular torso, gave everyone the feeling that he was a regular guy, and perhaps they too could express love and joy by dancing in the street or stomping through puddles...he democratized the dance in movies."^[18] In particular, he wanted to create a completely different image from that associated with Fred Astaire, not least because he believed his physique didn't suit such refined elegance: "I used to envy his cool aristocratic style, so intimate and contained. Fred wears top hat and tails to the manor born — I put them on and look like a truck driver."^[4]