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Thehistory of genetics dates from theclassical era with contributions byPythagoras,Hippocrates,Aristotle,Epicurus, and others. Modern genetics began with the work of theAugustinian friarGregor Johann Mendel.His works on pea plants, published in 1866, provided the initial evidence that, on its rediscovery in the 1900s, helped to establish the theory ofMendelian inheritance.
Inancient Greece, Hippocrates suggested that all organs of the body of a parent gave off invisible "seeds", miniaturised components that were transmitted during sexual intercourse and combined in the mother's womb to form a baby. In theearly modern period,William Harvey'sbookOn Animal Generation contradictedAristotle's theories of genetics and embryology.
The 1900 rediscovery of Mendel's work byHugo de Vries,Carl Correns andErich von Tschermak led to rapid advances in genetics. By 1915 the basic principles of Mendelian genetics had been studied in a wide variety of organisms – most notably the fruit flyDrosophila melanogaster. Led byThomas Hunt Morgan and his fellow "drosophilists", geneticists developed theMendelian model, which was widely accepted by 1925. Alongside experimental work, mathematicians developed the statistical framework ofpopulation genetics, bringing genetic explanations into the study ofevolution.
With the basic patterns of genetic inheritance established, many biologists turned to investigations of the physical nature of thegene. In the 1940s and early 1950s, experiments pointed toDNA as the portion of chromosomes (and perhaps other nucleoproteins) that held genes. A focus on new model organisms such as viruses and bacteria, along with thediscovery of the double helical structure of DNA in 1953, marked the transition to the era ofmolecular genetics.
In the following years, chemists developed techniques for sequencing both nucleic acids and proteins, while many others worked out the relationship between these two forms of biological molecules and discovered thegenetic code. The regulation ofgene expression became a central issue in the 1960s; by the 1970s gene expression could be controlled and manipulated throughgenetic engineering. In the last decades of the 20th century, many biologists focused on large-scale genetics projects, such as sequencing entire genomes.
The most influential early theories of heredity were that ofHippocrates andAristotle. Hippocrates' theory (possibly based on the teachings ofAnaxagoras) was similar to Darwin's later ideas onpangenesis, involving heredity material that collects from throughout the body.Aristotle suggested instead that the (nonphysical)form-giving principle of an organism was transmitted through semen (which he considered to be a purified form of blood) and the mother's menstrual blood, which interacted in the womb to direct an organism's early development.[1] For both Hippocrates and Aristotle—and nearly all Western scholars through to the late 19th century—theinheritance of acquired characters was a supposedly well-established fact that any adequate theory of heredity had to explain. At the same time, individual species were taken to have afixed essence; such inherited changes were merely superficial.[2] The Athenian philosopherEpicurus observed families and proposed the contribution of both males and females of hereditary characters ("sperm atoms"), noticed dominant and recessive types of inheritance and described segregation and independent assortment of "sperm atoms".[3]
The Roman poet and philosopherLucretius describes heredity in his work "De rerum natura".[4]
From this semen, Venus produces a varied variety of characteristics and reproduces ancestral traits of expression, voice or hair; These features, as well as our faces, bodies, and limbs, are also determined by the specific semen of our relatives.[5]
Similarly,Marcus Terentius Varro in "Rerum rusticarum libri tres" and Publius Vergilius Maro propose that wasps and bees originate from animals like horses, calves, and donkeys, with wasps coming from horses and bees from calves or donkeys.[6]
In 1000 CE, theArab physician,Abu al-Qasim al-Zahrawi (known as Albucasis in the West) was the first physician to describe clearly the hereditary nature ofhaemophilia in hisAl-Tasrif.[7] In 1140 CE,Judah HaLevi described dominant and recessive genetic traits inThe Kuzari.[8]
The preformation theory is a developmental biological theory, which was represented in antiquity by the Greek philosopherAnaxagoras. It reappeared in modern times in the 17th century and then prevailed until the 19th century. Another common term at that time was the theory of evolution, although "evolution" (in the sense of development as a pure growth process) had a completely different meaning than today. The preformists assumed that the entire organism was preformed in thesperm (animalkulism) or in theegg (ovism or ovulism) and only had to unfold and grow. This was contrasted by the theory ofepigenesis, according to which the structures and organs of an organism only develop in the course of individual development (Ontogeny). Epigenesis had been the dominant opinion since antiquity and into the 17th century, but was then replaced by preformist ideas. Since the 19th century epigenesis was again able to establish itself as a view valid to this day.[9][10]
In the 18th century, with increased knowledge of plant and animal diversity and the accompanying increased focus ontaxonomy, new ideas about heredity began to appear.Linnaeus and others (among themJoseph Gottlieb Kölreuter,Carl Friedrich von Gärtner, andCharles Naudin) conducted extensive experiments with hybridisation, especiallyhybrids between species. Species hybridisers described a wide variety of inheritance phenomena, include hybrid sterility and the high variability ofback-crosses.[11]
Plant breeders were also developing an array of stablevarieties in many important plant species. In the early 19th century,Augustin Sageret established the concept ofdominance, recognising that when some plant varieties are crossed, certain characteristics (present in one parent) usually appear in the offspring; he also found that some ancestral characteristics found in neither parent may appear in offspring. However, plant breeders made little attempt to establish a theoretical foundation for their work or to share their knowledge with current work of physiology,[12] althoughGartons Agricultural Plant Breeders in England explained their system.[13]
Between 1856 and 1865,Gregor Mendel conducted breeding experiments using the pea plantPisum sativum and traced the inheritance patterns of certain traits. Through these experiments, Mendel saw that the genotypes and phenotypes of the progeny were predictable and that some traits were dominant over others.[14] These patterns ofMendelian inheritance demonstrated the usefulness of applying statistics to inheritance. They also contradicted 19th-century theories ofblending inheritance, showing, rather, that genes remain discrete through multiple generations of hybridisation.[15]
From his statistical analysis, Mendel defined a concept that he described as a character (which in his mind holds also for "determinant of that character"). In only one sentence of his historical paper, he used the term "factors" to designate the "material creating" the character: " So far as experience goes, we find it in every case confirmed that constant progeny can only be formed when the egg cells and the fertilising pollen are off like the character so that both are provided with the material for creating quite similar individuals, as is the case with the normal fertilisation of pure species. We must, therefore, regard it as certain that exactly similar factors must be at work also in the production of the constant forms in the hybrid plants."(Mendel, 1866).
Mendel's work was published in 1866 as"Versuche über Pflanzen-Hybriden" (Experiments on Plant Hybridisation) in theVerhandlungen des Naturforschenden Vereins zu Brünn (Proceedings of the Natural History Society of Brünn), following two lectures he gave on the work in early 1865.[16]
Mendel's work was published in a relatively obscurescientific journal, and it was not given any attention in the scientific community. Instead, discussions about modes of heredity were galvanised byDarwin's theory ofevolution by natural selection, in which mechanisms of non-Lamarckian heredity seemed to be required. Darwin's own theory of heredity,pangenesis, did not meet with any large degree of acceptance.[17][18] A more mathematical version of pangenesis, one which dropped much of Darwin's Lamarckian holdovers, was developed as the "biometrical" school of heredity by Darwin's cousin,Francis Galton.[19]
In 1883August Weismann conducted experiments involving breeding mice whose tails had been surgically removed. His results — that surgically removing a mouse's tail had no effect on the tail of its offspring — challenged the theories of pangenesis andLamarckism, which held that changes to an organism during its lifetime could be inherited by its descendants. Weismann proposed thegerm plasm theory of inheritance, which held that hereditary information was carried only in sperm and egg cells.[20]
Hugo de Vries wondered what the nature of germ plasm might be, and in particular he wondered whether or not germ plasm was mixed like paint or whether the information was carried in discrete packets that remained unbroken. In the 1890s he was conducting breeding experiments with a variety of plant species and in 1897 he published a paper on his results that stated that each inherited trait was governed by two discrete particles of information, one from each parent, and that these particles were passed along intact to the next generation. In 1900 he was preparing another paper on his further results when he was shown a copy of Mendel's 1866 paper by a friend who thought it might be relevant to de Vries's work. He went ahead and published his 1900 paper without mentioning Mendel's priority. Later that same year another botanist,Carl Correns, who had been conducting hybridisation experiments with maize and peas, was searching the literature for related experiments prior to publishing his own results when he came across Mendel's paper, which had results similar to his own. Correns accused de Vries of appropriating terminology from Mendel's paper without crediting him or recognising his priority. At the same time another botanist,Erich von Tschermak was experimenting with pea breeding and producing results like Mendel's. He too discovered Mendel's paper while searching the literature for relevant work. In a subsequent paper de Vries praised Mendel and acknowledged that he had only extended his earlier work.[20]
After the rediscovery of Mendel's work there was a feud betweenWilliam Bateson andPearson over the hereditary mechanism, solved byRonald Fisher in his work "The Correlation Between Relatives on the Supposition of Mendelian Inheritance".
In 1910,Thomas Hunt Morgan showed that genes reside on specificchromosomes. He later showed that genes occupy specific locations on the chromosome. With this knowledge,Alfred Sturtevant, a member of Morgan's famousfly room, usingDrosophila melanogaster, provided the first chromosomal map of any biological organism. In 1928,Frederick Griffith showed that genes could be transferred. In what is now known asGriffith's experiment, injections into a mouse of a deadly strain ofbacteria that had been heat-killed transferred genetic information to a safe strain of the same bacteria, killing the mouse.
A series of subsequent discoveries (e.g.[21]) led to the realization decades later that the genetic material is made ofDNA (deoxyribonucleic acid) and not, as was widely believed until then, of proteins. In 1941,George Wells Beadle andEdward Lawrie Tatum showed that mutations in genes caused errors in specific steps ofmetabolic pathways.[22] This showed that specific genes code for specific proteins, leading to the "one gene, one enzyme" hypothesis.[23]Oswald Avery,Colin Munro MacLeod, andMaclyn McCartyshowed in 1944 that DNA holds the gene's information.[24] In 1952,Rosalind Franklin andRaymond Gosling produced a strikingly clear x-ray diffraction pattern indicating a helical form. Using these x-rays and information already known about the chemistry of DNA,James D. Watson andFrancis Crick demonstrated the molecular structure ofDNA in 1953.[25][26] Together, these discoveries established thecentral dogma of molecular biology, which states that proteins are translated fromRNA which is transcribed by DNA. This dogma has since been shown to have exceptions, such asreverse transcription inretroviruses.
In 1947, Salvador Luria discovered the reactivation of irradiated phage[27] leading to many further studies on the fundamental processes of repair of DNA damage (for review of early studies, see[28]). In 1958, Meselson and Stahl demonstrated that DNA replicates semiconservatively, leading to the understanding that each of the individual strands in double-stranded DNA serves as a template for new strand synthesis.[29] In 1960, Jacob and collaborators discovered theoperon which consists of a sequence of genes whose expression is coordinated by operator DNA.[30] In the period 1961 – 1967, through work in several different labs, the nature of the genetic code was determined (e.g.[31]).
In 1972,Walter Fiers and his team at theUniversity of Ghent were the first to determine the sequence of a gene: the gene forbacteriophage MS2 coat protein.[32]Richard J. Roberts andPhillip Sharp discovered in 1977 that genes can be split into segments. This led to the idea that one gene can make several proteins. The successful sequencing of many organisms'genomes has complicated the molecular definition of the gene. In particular, genes do not always sit side by side onDNA like discrete beads. Instead,regions of the DNA producing distinct proteins may overlap, so that the idea emerges that "genes are one longcontinuum".[33][34] It was first hypothesised in 1986 byWalter 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 serve both as a catalyst and as genetic information storage processor.
The modern study ofgenetics at the level of DNA is known asmolecular genetics, and the synthesis of molecular genetics with traditionalDarwinianevolution is known as themodern evolutionary synthesis.
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