In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce RNA. There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of RNA or protein from a gene), DNA is first copied into RNA. RNA can be directly functional or be the intermediate template for the synthesis of a protein.
Genes and their regulatory sequences are mainly responsible for determining the physical traits, or the phenotype of an organism. The genotype is the total amount of DNA in an organism including genes, other functional elements, and non-functional DNA.
A gene can acquire mutations in its sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a gene, which may be expressed as different phenotypic traits.
Populations evolve when the frequencies of alleles shift due mostly to natural selection and genetic drift. Some of these alleles are located in genes.
Definitions There are many different ways to use the term "gene" based on different aspects of their inheritance, selection, biological function, or molecular structure but most of these definitions fall into two categories, the Mendelian gene or the molecular gene.
The Mendelian gene is the classical gene of genetics and it refers to any heritable trait. In The Selfish Gene, Richard Dawkins argues that it is the unit of evolution. More thorough discussions of this version of a gene can be found in the articles Genetics and Gene-centered view of evolution.
The molecular gene definition is more commonly used across biochemistry, molecular biology, and most of genetics—the gene that is described in terms of DNA sequence. There are many different definitions of this gene—some of which are misleading or incorrect.
Very early work in the field that became molecular genetics suggested the concept that one gene makes one protein (originally 'one gene – one enzyme'). However, genes that produce repressor RNAs were proposed in the 1950s and by the 1960s, textbooks were using molecular gene definitions that included those that specified functional RNA molecules such as ribosomal RNA and tRNA (noncoding genes) as well as protein-coding genes.
This idea of two kinds of genes is still part of the definition of a gene in most textbooks. For example,
The important parts of such definitions are: (1) that a gene corresponds to a transcription unit; (2) that genes produce both mRNA and noncoding RNAs; and (3) regulatory sequences control gene expression but are not part of the gene itself. However, there is one other important part of the definition and it is emphasized in Kostas Kampourakis' book Making Sense of Genes.
The emphasis on function is essential because there are stretches of DNA that produce non-functional transcripts and they do not qualify as genes. These include obvious examples such as transcribed pseudogenes as well as less obvious examples such as junk RNA produced as noise due to transcription errors. In order to qualify as a true gene, by this definition, one has to prove that the transcript has a biological function.
Early speculations on the size of a typical gene were based on high-resolution genetic mapping and on the size of proteins and RNA molecules. A length of 1500 base pairs seemed reasonable at the time (1965). This was based on the idea that the gene was the DNA that was directly responsible for production of the functional product. The discovery of introns in the 1970s meant that many eukaryotic genes were much larger than the size of the functional product would imply. Typical mammalian protein-coding genes, for example, are about 62,000 base pairs in length (transcribed region) and since there are about 20,000 of them they occupy about 35–40% of the mammalian genome (including the human genome).
In spite of the fact that both protein-coding genes and noncoding genes have been known for more than 50 years, there are still a number of textbooks, websites, and scientific publications that define a gene as a DNA sequence that specifies a protein. In other words, the definition is restricted to protein-coding genes. Here is an example from a 2021 article in American Scientist.
This restricted definition is so common that it has spawned many recent articles that criticize this "standard definition" and call for a new expanded definition that includes noncoding genes. However, some modern writers still do not acknowledge noncoding genes although this so-called "new" definition has been recognised for more than half a century.
Although some definitions can be more broadly applicable than others, the fundamental complexity of biology means that no definition of a gene can capture all aspects perfectly. Not all genomes are DNA (e.g. RNA viruses), bacterial operons are multiple protein-coding regions transcribed into single large mRNAs, alternative splicing enables a single genomic region to encode multiple distinct products and trans-splicing concatenates mRNAs from shorter coding sequence across the genome. Since molecular definitions exclude elements such as introns, promotors, and other regulatory regions, these are instead thought of as "associated" with the gene and affect its function.
An even broader operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions.
History
Discovery of discrete inherited units
The existence of discrete heritable units was discovered by Gregor Mendel. From 1857 to 1864, in Brno, Austrian Empire (today's Czech Republic), he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured Wilhelm Johannsen's distinction between genotype (the genetic makeup of an organism) and phenotype (the observable traits of that organism). Mendel was also the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the phenomenon of discontinuous inheritance.
Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which suggested that each parent contributed fluids to the fertilization process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan ("all, whole") and genesis ("birth") / genos ("origin"). Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction.
Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries, Carl Correns, and Erich von Tschermak, who (claimed to have) reached similar conclusions in their own research. In 1889, de Vries published Intracellular Pangenesis, Translated in 1908 from German to English by Open Court Publishing Co., Chicago, 1910 in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. He called these units "pangenes" (Pangens in German), after Darwin's 1868 pangenesis theory.
In 1906, William Bateson coined "genetics" (from Greek, γενετικός genetikos meaning "genitive"/"generative")." In 1909, Johannsen introduced the term "gene" (from the Greek: γόνος, gonos, meaning offspring and procreation). From p. 124: "Dieses "etwas" in den Gameten bezw. in der Zygote, ... – kurz, was wir eben Gene nennen wollen – bedingt sind." (This "something" in the gametes or in the zygote, which has crucial importance for the character of the organism, is usually called by the quite ambiguous term Anlagen [primordium, from the German word Anlage for "plan, arrangement; rough sketch"]. Many other terms have been suggested, mostly unfortunately in closer connection with certain hypothetical opinions. The word "pangene", which was introduced by Darwin, is perhaps used most frequently in place of Anlagen. However, the word "pangene" was not well chosen, as it is a compound word containing the roots pan (the neuter form of Πας all, every) and gen (from γί-γ(ε)ν-ομαι, to become). Only the meaning of this latter [i.e., gen] comes into consideration here; just the basic idea – [namely,] that a trait in the developing organism can be determined or is influenced by "something" in the gametes – should find expression. No hypothesis about the nature of this "something" should be postulated or supported by it. For that reason it seems simplest to use in isolation the last syllable gen from Darwin's well-known word, which alone is of interest to us, in order to replace, with it, the poor, ambiguous word Anlage. Thus we will say simply "gene" and "genes" for "pangene" and "pangenes". The word gene is completely free of any hypothesis; it expresses only the established fact that in any case many traits of the organism are determined by specific, separable, and thus independent "conditions", "foundations", "plans" – in short, precisely what we want to call genes.) Eduard Strasburger, among others, still used the term "pangene" for the fundamental physical and functional unit of heredity.
Discovery of DNA
Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA) was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s. Reprint: The structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication.
In the early 1950s the prevailing view was that the genes in a chromosome acted as discrete entities arranged like beads on a string. The experiments of Seymour Benzer using mutants defective in the rII region of bacteriophage T4 (1955–1959) showed that individual genes have a simple linear structure and are likely to be equivalent to a linear section of DNA.
In 1965, the lab of Max Birnstiel was the first to isolate single genes, the ribosomal RNA genes from Xenopus laevis. In 1972, Walter Fiers and his team were the first to determine the sequence of a gene: that of bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool. An automated version of the Sanger method was used in early phases of the Human Genome Project.
Modern synthesis and its successors
R. A. Fisher, Sewall Wright and J.B.S. Haldane integrated Mendelian genetics with Darwinian evolution in the modern synthesis, a term introduced by Julian Huxley.
W. D. Hamilton, George C. Williams and John Maynard Smith developed the gene-centric view of evolution, which argued that the Mendelian gene is a unit of natural selection. Williams defined the gene in this view: "that which segregates and recombines with appreciable frequency."Richard Dawkins popularized this view in several books, starting with The Selfish Gene.