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 Sperling
Sperling at the Financial Times View from the Top conference (2011)
Director of the National Economic Council
Incumbent
Assumed office January 20, 2011
President	Barack Obama
Preceded by	Lawrence Summers
In office December 1996 – 2000
President	Bill Clinton
Preceded by	Laura Tyson
Succeeded by	Lawrence Lindsey
Personal details
Born	(1958-12-24) December 24, 1958 (age 53) Ann Arbor, Michigan, U.S.
Political party	Democratic Party
Alma mater	University of Minnesota, Twin Cities Yale University University of Pennsylvania

Gene B. Sperling (born December 24, 1958) is an American lawyer and political figure,^[1] currently serving as Director of the National Economic Council under President Obama.^[2]

Life and career[link]

Sperling was born in Ann Arbor, Michigan, where he attended the alternative Community High School. He received a B.A. in political science from the University of Minnesota, a J.D. from Yale Law School, and attended The Wharton School of the University of Pennsylvania. In the 1990s Gene Sperling worked for New York Governor Mario Cuomo.

During Bill Clinton's first term as President, from 1993–1996, Sperling served as deputy director of the National Economic Council while the Council was directed by Robert Rubin, who was promoted to Treasury Secretary. Sperling became National Economic Adviser to Clinton and director of the National Economic Council from 1996 to 2000.

As director of the NEC, Sperling, who had played a key role in the 1993 Deficit Reduction Act, was a key negotiator of the 1997 bipartisan Balanced Budget Act.^[3]. Sperling was also a principal negotiator with then-Treasury Secretary Lawrence Summers of the Financial Modernization Act of 1999, also known as the Gramm-Leach-Bliley Act. Gramm-Leach-Bliley repealed large portions of the depression-era Glass-Stegall Act allowing banks, securities firms and insurance companies to merge.^[4] President Barack Obama believes that the repeal of Glass–Steagall helped cause the 2007 subprime mortgage financial crisis.^[5]

Also in 1999, together with United States Trade Representative Charlene Barshefsky, Sperling successfully negotiated and concluded the China-World Trade Organization agreement in Beijing, paving the way for China to enter the WTO in 2001.^[6]

Sperling was the chief economic advisor for Hillary Clinton during her presidential campaign.^[7][8]

Sperling was also on the staff of the Council on Foreign Relations, where he founded and served as director of the Center for Universal Education—an organization focused on ensuring quality, universal education for the world’s poorest children.^[9]

According to Bloomberg News, Sperling earned $887,727 from Goldman Sachs in 2008 for advice on its charitable giving and $158,000 for speeches mostly to financial companies.^[10]

Sperling is the author of The Pro-Growth Progressive, a book arguing that liberals should seek to harness market forces in pursuing progressive goals, and co-author of What Works In Girls' Education?. He was also a consultant for the television series The West Wing.

From 2009 to 2011, Sperling served as a counselor to Treasury Secretary Timothy Geithner, advising on fiscal, budget, tax, job creation and small business issues.^[11]

In January 2011, President Barack Obama appointed Sperling as the director of the National Economic Council.

Works[link]

• Dellinger, Walter; Sperling, Gene B. (1989). "Abortion and the Supreme Court: The Retreat from Roe v. Wade". University of Pennsylvania Law Review 138 (1): 83–118. JSTOR 3312180. 
• Herz, Barbara; Sperling, Gene B. (2004). What Works In Girls' Education: Evidence And Policies From The Developing World. New York: Council on Foreign Relations Press. ISBN 0-87609-344-6. 
• Sperling, Gene B. (1985). "Judicial Right Declaration and Entrenched Discrimination". Yale Law Journal 94 (7): 1741–1765. JSTOR 796220. 
•     (2001). "Toward Universal Education: Making a Promise, and Keeping It". Foreign Affairs 80 (5): 7–13. JSTOR 20050246. 
•     (2005). The Pro-Growth Progressive: An Economic Strategy for Shared Prosperity. New York: Simon & Schuster. ISBN 0-7432-3753-6. 
• Treanor, William Michael; Sperling, Gene B. (1993). "Prospective Overruling and the Revival of 'Unconstitutional' Statutes". Columbia Law Review 93 (8): 1902–1955. JSTOR 1123007. 

Important H1B Visa Power Broker[link]

In the history of the H-1B program, few people have played a role as important as that of Gene Sperling, who was appointed by President Obama to head the National Economic Council.^[12]

References[link]

External links[link]

• Official page on the site of the Council on Foreign Relations
• Commonwealth Club of California, archived speech
• "The Pro-Growth Progressive" - Gene Sperling speaks at Google
• Obama appointee Sperling was key H-1B broker

This article has multiple issues. Please help improve it or discuss these issues on the talk page. This biography of a living person needs additional citations for verification. Tagged since August 2011. It relies on references to primary sources or sources affiliated with the subject, rather than references from independent authors and third-party publications. Tagged since August 2011.

Gene Simmons
Gene Simmons on stage with Kiss, 2010
Background information
Birth name	Chaim Weitz ( /ˈxɑːjɪm/; ‏Hebrew: חיים ויץ‎)
Also known as	"The Demon"
Born	(1949-08-25) August 25, 1949 (age 62) Tirat HaCarmel, Israel
Genres	Heavy metal, hard rock
Occupations	Musician, songwriter, producer, actor, entrepreneur
Instruments	Bass, vocals, guitar, piano
Years active	1960–present
Associated acts	Kiss, Wicked Lester
Website	www.genesimmons.com
Notable instruments
Cort Signature GS-1 Gene Simmons Signature model

Gene Simmons (born Chaim Weitz Hebrew: חיים ויץ‎; August 25, 1949) is an Israeli-American rock bassist, singer-songwriter, entrepreneur and actor. Known as "The Demon", he is the bassist/co-vocalist of Kiss, a hard rock band he co-founded in the early 1970s. Kiss has sold over 100 million albums worldwide.

Biography[link]

Early life[link]

Chaim Weitz (later Gene Simmons) was born at the Rambam Hospital in Haifa, Israel in 1949. Mother and child emigrated to Jackson Heights, Queens in New York City when he was eight years old.^[1] His mother Flóra "Florence" Klein (formerly Kovács) was born in Jánd, Hungary. The German name Klein (means: small) is sometimes used informally in Hungarian as Kis, this however, did not give the band its name.^[2] Florence and her brother, Larry Klein, were the only members of the family to survive the Holocaust. Simmons' father, Feri Witz, also Hungarian-born, remained in Israel, where he had one other son and three daughters. Simmons says the family was "dirt poor," scraping by on bread and milk.^[3] In the United States, Simmons changed his name to Eugene Klein (later Gene Klein), adopting his mother's maiden name. He was a part of Yeshiva Torah Vodaath in Williamsburg, Brooklyn as a child, from 7 am to 9:30 pm^[4]

Kiss[link]

Simmons became involved with his first band, Lynx, then renamed The Missing Links, when he was a teenager. Eventually, he disbanded The Missing Links to form The Long Island Sounds, the name being a play on words relating to the estuary separating Long Island from Westchester County, New York, Connecticut and Rhode Island. While he played in these bands, he kept up odd jobs on the side to make more money, including trading used comic books. Simmons attended Sullivan County Community College in Loch Sheldrake, New York. He then joined a new band, Bullfrog Bheer, and the band recorded a demo, "Leeta"; this was later included on the Kiss box set.

Gene Simmons fire breathing.

Simmons formed the rock band Wicked Lester in the early 1970s with Stanley Harvey Eisen (now known as Paul Stanley) and recorded one album, which was never released. Dissatisfied with Wicked Lester's sound and look, Simmons and Stanley attempted to fire their band members; they were met with resistance, and they quit Wicked Lester, walking away from their record deal with Epic Records. They decided to form the ultimate rock band, and started looking for a drummer. Simmons and Stanley found an ad placed by Peter Criscoula, known as Peter Criss, who was playing clubs in Brooklyn at the time; they joined and started out as a trio. Paul Frehley, better known as Ace Frehley, responded to an ad they put in The Village Voice for a lead guitar player, and soon joined them. Kiss released its self-titled debut album in February 1974. Stanley took on the role of lead performer on stage, while Simmons became the driving force behind what became an extensive Kiss merchandising franchise. The eye section of his "Vampire" makeup with KISS came from the wing design of comic book character Black Bolt.^[5]

In 1983, while Kiss' fame was waning, the members took off their trademark make-up and enjoyed a resurgence in popularity that continued into the 1990s. At this time, Peter Criss the original drummer quit the band, and a replacement was sought to fill the drummers vacancy. The drummer that did so, was Paul Charles Caravello, who went by the stage name of Eric Carr, and played for KISS from 1980 until his early death at the age of 41 in 1991. The band hosted their own fan conventions throughout 1995, and fan feedback about the original Kiss members reunion influenced the highly successful 1996–1997 Alive Worldwide reunion tour. In 1998, the band released Psycho Circus. Since then, the original line-up has once again dissolved, with Tommy Thayer replacing Ace Frehley on lead guitar and Eric Singer (who performed with Kiss from 1992 up through 1996) replacing Peter Criss on drums.

Stage makeup and persona[link]

During an interview in 1999, Simmons was asked about the source and significance of Kiss' stage makeup and personas:

I've always been a fan of Americana, and Americana has always been about imagery, often above content. I think there's nothing wrong with that. The world worships this culture. Most people only think about America in terms of rock & roll, movies and television. Kiss is very all-American, in the sense that our constituency has never had anything in common with critics . . . because our power, our lifeblood, our very reason for existence is our fans. Without them, we'd be nothing. Rock & roll is, in fact, all about gimmicks. Most people love gimmicks. I love gimmicks — Jerry Lee Lewis getting up and playing the piano with his foot. I love all of it — anything that puts on a show, where the performer makes a spectacle of himself — and that's everything we've ever been devoted to. If people think of Kiss as performers first and musicians or anything else later, that's wonderful. It's the most boring thing to be known as a musician, because those guys eventually wind up playing Holiday Inns.^[6]

Gene Simmons without make-up.

Political views[link]

Simmons was a supporter of the foreign policy of the George W. Bush administration.^[7] He supported the 2003 invasion of Iraq, writing on his website: "I'm ashamed to be surrounded by people calling themselves liberal who are, in my opinion, spitting on the graves of brave American soldiers who gave their life to fight a war that wasn't theirs...in a country they've never been to... simply to liberate the people therein".^[8] In a follow-up, Simmons explained his position and wrote about his love and support for the United States: "I wasn't born here. But I have a love for this country and its people that knows no bounds. I will forever be grateful to America for going into World War II, when it had nothing to gain, in a country that was far away... and rescued my mother from the Nazi German concentration camps. She is alive and I am alive because of America. And, if you have a problem with America, you have a problem with me".^[8]

During the 2006 Lebanon War between Israel and Lebanon, Simmons sent a televised message of support (in both English and Hebrew) to an Israeli soldier seriously wounded in fighting in Lebanon, calling him his "hero".^[9]

In 2010, Simmons said he regretted voting for Barack Obama and criticized the 2009 health care reforms.^[10] Following Obama's 2011 Mideast speech, in which the President called on Israel and the Palestinians to negotiate a settlement "based on the 1967 lines with mutually agreed swaps,"^[11] Simmons told CNBC that Obama was gravely misguided. "If you have never been to the moon, you can't issue policy about the moon. For the president to be sitting in Washington D.C. and saying, 'Go back to your '67 borders in Israel' – how about you live there and try to defend an indefensible border – nine miles wide?" Simmons also accused the United Nations of being "the most pathetic body on the face of the earth."^[12]

During his visit to Israel in 2011, he stated that the artists refusing to perform in Israel for political reasons are "stupid," referring to artists who canceled planned concerts in Israel.^[13]

In an April 2012 interview, Simmons endorsed Republican Mitt Romney for President, stating as well that "America should be in business and it should be run by a businessman."^[14]

Personal life[link]

He became a science fiction fan and published several science fiction fanzines, among them Sirruish, Id, Cosmos (which eventually merged with Stilletto to become Cosmos-Stilletto and then Faun), Tinderbox, Sci-Fi Showcase, Mantis and Adventure. He also contributed to other fanzines, among them BeABohema.^[15]

In the late 1960s, he changed his name to Gene Simmons, after legendary rockabilly performer Jumpin' Gene Simmons.^[16] Simmons' legal name after arriving from Israel is Gene Klein.

Simmons lives in Beverly Hills, California with former Playboy Playmate and actress Shannon Tweed whom he had dated for 28 years. He often joked that he and Tweed were "happily unmarried" for over 20 years. He often stated, "Marriage is an institution, and I don't want to live in an institution." Simmons and Tweed finally wed on October 1, 2011, at the historic Beverly Hills Hotel in Beverly Hills, California.^[17][18] They have two children: a son, Nick (born January 22, 1989), and a daughter, Sophie Alexandra (born July 7, 1992). He formerly had live-in relationships with Cher and Diana Ross.^[1] Simmons can speak English, German, Hungarian and Hebrew.^[1]

Homecoming visit to Israel[link]

In March 2011, Simmons visited Israel, where he was born. He described the trip as a "life changing experience". He talked about how he still feels that he is an Israeli: "I'm Israeli. I'm a stranger in America. I'm an outsider".^[19] While there, Gene met his half-brother Kobi, and triplet half-sisters Drora, Sharon and Ogenia.^[20] Simmons has plans to bring his band, KISS, to Israel. He has always said that he is an ardent supporter of Israel.^[21] At a press conference in Israel, he spoke both Hebrew and English.^[22]

Controversy[link]

• In February 2002, Simmons was interviewed on the NPR radio show Fresh Air and asked about his claim of having had sex with 4,600 women. He told Terry Gross: "If you want to welcome me with open arms, I'm afraid you're also going to have to welcome me with open legs," paraphrasing a lyric from The Who's 1981 hit song "You Better You Bet". Gross replied: "That's a really obnoxious thing to say." At the time, Simmons refused to grant permission to NPR to make the interview available online.^[23] However, it appears in print in Gross's book All I Did Was Ask (ISBN 1-4013-0010-3) and unauthorized transcripts are available. NPR re-broadcast part of the interview in August 2007.^[24] Simmons' bandmate Paul Stanley has frequently used the phrase "... welcomed us with open arms and open legs" in onstage patter during Kiss concerts.
• In 2004, during an interview in Melbourne, Australia, while talking about Islamic extremists, Simmons described Islam as a "vile culture", saying that Muslim women had to walk behind their husbands, were not allowed to be educated or to own houses. He said: "They want to come and live right where you live and they think that you're evil." Amongst ensuing criticism, Australian Muslim of the Year Susan Carland argued that Simmons' stereotyping of Muslims was inaccurate.^[25] Simmons later clarified his comments on his website, saying he had been talking specifically about Muslim extremists.
• In 2005, Simmons was sued by a former girlfriend, Georgeann Walsh Ward, who said she had been "defamed" in the VH1 documentary When Kiss Ruled the World and portrayed as an "unchaste woman".^[26] A settlement was reached in June 2006.^[27]
• In 2007, Simmons openly spoke out against music piracy, and called for file-sharers to be sued.^[28] A year later, he threatened further lawsuits, and to withhold new recordings, if file-sharing continued.^[29] In 2010, Anonymous staged a DDoS on his Web site, prompting Simmons to hit back with provocative comments once he was back online.^[29]
• In 2011, Kiss was removed from the lineup for Michael Jackson's tribute concert because of Simmons' allegations and negative comments regarding Jackson's personal life and legal issues.^[30]

Instruments[link]

Gene Simmons' axe bass at the Hard Rock Cafe in Seattle, Washington

Gene Simmons has used various bass guitars during his career including:

• Axe Bass (Kramer, Jackson, B.C. Rich and now Cort)
• Punisher Bass (B.C.Rich, now made by Cort)
• Spector Gene Simmons Signature
• Pedulla Basses (mainly in the 1980s and early 1990s)
• Gibson Grabber (mainly in Kiss' early years)
• Gibson Ripper (mainly in Kiss' early years)
• Custom lebau bass (Wicked Lester, very early kiss circa 73–74)
• Cort Guitars Signature GS-1 Bass

He uses Ampeg SVT CL Series amps with 8x10 cabinets. He uses Silver Herco Flex .75 Nylon Flat Guitar Picks. He uses D'Addario EXL165 Nickel Wound Custom Light 45-105 Long Scale Bass Strings. In 2010 Gene Simmons collaborated with Cort Guitars to make his own signature bass line called the GS-AXE-2.

Film and television career[link]

Simmons has been the creative force behind such television projects as:

• My Dad the Rock Star, a cartoon by the Canadian animation company Nelvana, about the mild mannered son of a Gene Simmons-like rock star;
• Mr. Romance, a show created and hosted by Simmons on the Oxygen cable television channel;
• Rock School, a reality show in which Simmons tries to make a rock band out of a group of students of Christ's Hospital School in the first season, and in the second, a group of kids from a comprehensive school in Lowestoft;
• Gene Simmons Family Jewels,^[31] a reality show documenting the personal lives of Simmons, his wife, his son and daughter

On March 9, 2011, Simmons and Kiss co-founder Paul Stanley and E! Entertainment announced that they have finalized a production and development deal to create an as-yet-untitled comedic half-hour kids' television series.^[32] Simmons appeared as a psychic working at the Mystic Journey Bookstore in Venice, California on the American hidden camera prank TV series I Get That a Lot.^[33]

Awards and recognition[link]

On January 28, 2011, Simmons was in Dallas, Texas to host the Aces & Angels Salute to the Troops charity event. While in Dallas, Simmons was presented the key to the city in Dallas, Texas and a street, Gene Simmons Boulevard, was named for him. Simmons and Tweed also visited Ft. Hood to support the Troops as a part of the Aces & Angels event. On June 15 of the same year he was given the key to the city in Winnipeg, Manitoba. In 2012, Simmons was awarded the Golden God award by the Revolver magazine.^[34]

Filmography[link]

Television appearances[link]