The Genetics (modern neologism to ancient Greek γενεά genea "descent" and γένεσις genesis "origin") or genetics (formerly also genetic biology ) is the science of heredity and a branch of biology . It deals with the laws and material principles of the development of hereditary traits and the transmission of hereditary traits ( genes ) to the next generation .
The knowledge that individual characteristics are passed on over several generations is relatively new; Concepts of such natural processes of inheritance did not take shape until the 18th and early 19th centuries. The Augustinian monk Gregor Mendel is considered to be the founder of genetics in this sense.He systematically carried out cross-breeding experiments with peas in the garden of his monastery between 1856 and 1865 and evaluated them statistically . This is how he discovered Mendel's rules , which were later named after him, but which were not accepted and confirmed in science until 1900. By far the most important part of genetics today is molecular genetics , which deals with the molecular basis of inheritance. From it went genetic engineering evident in the findings of molecular genetics are applied in practice.
The adjective "genetic" was used as early as 1800 by Johann Wolfgang von Goethe in his work on the morphology of plants and in the subsequent period frequently in romantic natural philosophy and in descriptive embryology . Unlike today, it meant a method (“genetic method”) for examining and describing the individual development ( ontogenesis ) of organisms. The noun "genetics" was first used by William Bateson in 1905 to denote the new research discipline.
In Germany, until the second half of the 20th century, the expression “hereditary biology” was used with the same meaning, mostly to distinguish “hereditary biology of humans” ( human genetics ) from general genetics. The term "human genetics" was already established in Germany around 1940. This indicated a withdrawal to scientifically required basic research, while “ racial hygiene ” represented applied science. After 1945 the terms “hereditary biology” and “racial hygiene” gradually disappeared from scientific usage.
- The classical genetics founded by Mendel investigates the combinations in which the genes appear in cross-breeding experiments in the offspring ( Mendel's rules ) and how this influences the expression of certain phenotypic characteristics . Classical genetics also includes cytogenetics , which examines the number, shape and structure of the chromosomes as carriers of genetic information in the light microscopic size range .
- Molecular genetics - a branch of molecular biology - examines the molecular basis of inheritance: the structure of the molecular carriers of genetic information (usually DNA , in some viruses RNA ), the multiplication of these macromolecules ( replication ) and the resulting changes in the information content ( mutations , recombination ) as well as the realization of the genetic information in the course of gene expression ( transcription and translation ). Molecular genetics also includes genetic engineering as an applied area .
- The population genetics and ecological genetics study genetic structures and processes at the level of populations and other ecological units (z. B. whole communities).
- The epigenetics deals with the transfer of properties to the offspring, which are not to deviations in the DNA sequence to decline, but to heritable changes in gene regulation .
- 1866 - Gregor Mendel published his experiments on plant hybrids , but they received little attention.
- 1869 - Friedrich Miescher isolated the "nucleus" from cell nuclei, the structure and function of which initially remained a mystery.
- 1889 - Richard Altmann identified the " nucleic acid " and a basic protein fraction as components of the nuclein.
- 1900 - Hugo de Vries , Carl Correns and Erich Tschermak confirmed Mendel's discoveries.
- 1903 - Chromosomes were recognized as carriers of genetic information ( Walter Sutton ).
- 1906 - William Bateson coined the term genetics .
- 1907 - Thomas Hunt Morgan chose the fruit fly Drosophila melanogaster as an experimental animal.
- 1909 - Wilhelm Johannsen coined the term gene .
- 1927 - Artificial mutations triggered by X-rays ( Hermann Joseph Muller )
- 1928 - First description of the transformation by Frederick Griffith ( Griffith's experiment )
- 1931 - Cytological investigation of the crossing-over ( Barbara McClintock , Harriet B. Creighton , Curt Stern )
- 1940 - George Beadle and Edward Tatum formulated the one-gene-one-enzyme hypothesis .
- 1943 - The Luria-Delbrück experiment showed that mutations are random in the sense that they are not environmental reactions.
- 1944 - Oswald Avery , Colin MacLeod and Maclyn McCarty : Transformation of Bacteria by DNA
- 1950 - Erwin Chargaff showed with the Chargaff rules that the four nucleotides occur in pairs with the same frequency in the DNA: [A] = [T] and [C] = [G].
- 1951 - McClintock first reported on jumping genes but was met with complete misunderstanding.
- 1952 - The Hershey Chase experiment showed that the genetic information of bacteriophages is stored in DNA.
- 1953 - James Watson and Francis Crick postulated the double helix structure of DNA.
- 1957 - Proof of the semiconservative replication of the DNA and the crossing-over by James Herbert Taylor ( Taylor experiment )
- 1958 - Detection of the semiconservative replication of DNA by Meselson and Stahl
- 1958 - Crick postulated the " central dogma " of molecular genetics.
- 1961 - François Jacob and Jacques Monod introduced the Operon concept
- 1961 to 1965 - deciphering the genetic code ( Marshall Warren Nirenberg and Heinrich Matthaei )
- 1969 - Jonathan Beckwith was the first to isolate a single gene (from E. coli ).
- 1969 - Werner Arber , Daniel Nathans and Hamilton Othanel Smith discovered the restriction enzymes .
- 1975 - DNA sequencing ( Frederick Sanger , Allan Maxam , Walter Gilbert )
- 1977 - Intron - exon structure of eukaryotic genes
- 1983 - Kary Mullis developed the polymerase chain reaction (PCR) to amplify DNA.
- 1995 - The first prokaryotic genome (from Haemophilus influenzae ) was sequenced.
- 1997 - The first eukaryotic genome, that of the baker's yeast Saccharomyces cerevisiae , is sequenced
- 2003 - As a result of the Human Genome Project , the reference sequence of the human genome is available for download from the Internet
Even in ancient times people tried to explain the laws of procreation and the similarities between relatives, and some of the concepts developed in ancient Greece remained valid up to modern times or were taken up again in modern times. The Greek philosopher Alkmaion taught around 500 BC. BC that the procreation of the offspring takes place through the cooperation of the male and the female " seed ". His postulate of a female seed found general recognition in the natural philosophy of the time and later also in Hippocratic medicine. Contrary to this, Hippon and Anaxagoras claimed that only men produce fertile seeds and that the female organism only nourishes the germ. According to Alkmaion, the semen is formed in the brain, from where it reaches the testicles through the veins . In contrast, Anaxagoras and Democritus declared that the entire organism contributes to the formation of the semen - a view that was reiterated as the pangenesis theory more than 2000 years later by Charles Darwin . The considerations of Anaxagoras, according to which all parts of the child's body are already formed in the semen (sperm), reappeared as a preformation theory in modern times. In antiquity, these early teachings were largely superseded by the views of Aristotle ( De generatione animalium ), according to which sperm arises from the blood and only has an immaterial effect during conception by transferring form and movement to the liquid matter provided by the female organism . Aristotle described the development of the germ as an epigenesis , according to which, in contrast to the preformation, the various organs are formed one after the other through the influence of the paternal form principle. In addition to sexual generation, Aristotle was also familiar with parthenogenesis (virgin generation) and the (supposed) spontaneous generation of insects from putrefactive substances.
Theophrastus , a student of Aristotle, postulated a transmutatio frumentorum and assumed that cereals can revert to their wild form. He also differentiated between male and female plants in the date palm.
Inheritance was a legal term until the 18th century and was not used for natural processes. Similarities between relatives were sufficiently explained by specific local factors and the individual's way of life: the climate, diet, type of activity, etc. Like certain characteristics among offspring, these factors also remained constant for the offspring. Irregular characteristics could then be traced back to irregular influences in the conception or development of the individual. Only with increasing international traffic and, for example, the creation of exotic gardens, was a space created to allow the individual and his respective place to have detachable, natural laws that both pass on regular properties and sometimes pass on newly acquired properties regulate.
The concept of procreation or reproduction , in the context of which one can speak of heredity in the biological sense, only emerged towards the end of the 18th century. In earlier centuries, the "procreation" of a living being was considered an act of creation , which basically required divine intervention and was often viewed as part of the creation of the world within the framework of preformism. A distinction was made between the generation by the semen (sperm) in the womb and the spontaneous generation by which lower animals (such as worms, insects, snakes and mice) seemed to emerge from dead matter. The "sperm generation" was viewed as a peculiarity of humans and higher animals, which require a womb for their formation. It was only towards the end of the 17th century, mainly due to the experiments of Francesco Redi , that the insight gained acceptance that worms, insects and other lower animals do not arise from dead matter, but are created by animals of the same kind. Now procreation was no longer viewed as an act of creation, but relocated to the time of the creation of the world, during which it was assumed that all future generations of living beings were created nested at the same time. The procreation was therefore only an activation of the long-existing germ, which then developed into a fully developed organism. It was disputed whether the germs are passed on by the female or the male sex, i.e. whether they are nested in the egg or in the "seed animal". Both views have their supporters (ovists and animalculists) until the discovery of parthenogenesis in the aphid by Charles Bonnet in 1740 decided the dispute in favor of ovists.
In addition to the very popular preformation theory, which was brought into play in 1625 by Giuseppe degli Aromatari (1587–1660), there were also renowned followers of Aristotle's doctrine of Epigenesis in the 17th century, namely William Harvey and René Descartes . Their views, however, were considered antiquated and were rejected as unscientific, as they presupposed immaterial operating principles, while the preformism could be thought of in a purely mechanistic way and was also greatly boosted by the introduction of the microscope.
The idea of the preformation prevailed well into the 19th century, although there were research results that could not be reconciled with it. Great astonishment called the attempts at regeneration in salamanders , freshwater polyps produce and other animals. Polyps can be finely chopped up and, as Abraham Trembley described in 1744, each piece develops into a complete animal within two to three weeks. In the years 1744 to 1754 Pierre-Louis Moreau de Maupertuis published several writings in which he criticized and rejected the theory of preformation based on observations in animals and humans, according to which both parents can pass on characteristics to their offspring. Similar observations were also published by Joseph Gottlieb Kölreuter (1761), who was the first to study crossings of different plant species. And in 1759 Caspar Friedrich Wolff meticulously described the development of the embryo in the hen egg from completely undifferentiated matter. Despite the problems posed by such research, the theory of preformations only began to falter in the early 19th century due to the embryological studies of Christian Heinrich Pander (1817) and Karl Ernst von Baer (1828), in which they clarified the importance of the germ layers and showed generally valid laws of embryogenesis in animals.
With the establishment of the general cell theory developed by Matthias Jacob Schleiden (1838), Theodor Schwann (1839) and Rudolf Virchow (1858) it became clear that the reasons for the similarity of parents and offspring must be localized in the cell . All organisms consist of cells, growth is based on the proliferation of cells through division , and in sexual reproduction , which is the normal case in multicellular animals, one germ cell of both sexes unite to form a zygote , from which the new organism through continuous division and differentiation emerges.
The laws of inheritance remained in the dark for a long time. As early as 1799 to 1823, Thomas Andrew Knight - like Gregor Mendel a few decades later - carried out crossbreeding experiments with peas in which he observed the phenomena of dominance and the splitting of traits. In 1863 Charles Victor Naudin (1815–1899) published the results of his cross-breeding experiments with numerous plant genera, whereby he noted the very similar appearance of all plants of the first daughter generation and the "extreme diversity of forms" in the following generations and thus other significant aspects of the almost simultaneous Mendel's findings anticipated, but, unlike Mendel, did not carry out any statistical analysis.
The decisive breakthrough was achieved by Mendel with his attempts at crossing which he began in 1856, in which he concentrated on individual features and statistically evaluated the data obtained . In this way he was able to determine the basic principles of the distribution of genetic makeup among the offspring, which are now known as Mendel's rules . These discoveries, which he published in 1866, initially remained almost unnoticed by experts and were only rediscovered in 1900 by Hugo de Vries , Carl Correns and Erich Tschermak and confirmed on the basis of their own experiments.
The germline or germplasm theory , which August Weismann developed in the 1880s, brought about a radical change in ideas about heredity . Since ancient times it has been taken for granted that traits that the parents acquired during their life can be passed on to their offspring. According to Jean-Baptiste de Lamarck , in whose theory of evolution she played an important role, this view is now called Lamarckism . However, Charles Darwin also postulated in his pangenesis theory that the entire parental organism affects the germ cells - including indirectly through telegonia . Weismann now differentiated between the germ line , on which the germ cells of an organism are derived from the zygote, and the soma as the totality of all other cells from which no germ cells can emerge and from which no effects on the germ line proceed. However, this theory was initially very controversial.
With his two-volume work Die Mutationstheorie (1901/03), de Vries introduced the term " mutation ", which had been used in palaeontology until then, into heredity. In his opinion, mutations are extensive, sudden changes through which a new species emerges. In doing so, he relied on his studies on evening primrose , in which a plant had appeared that was "strongly changed in all of its organs", the characteristics of which proved to be inherited and which he therefore described as a new species ( Oenothera gigas ). (It was later revealed that Oe gigas. Unlike the diploid starting plants tetraploid was thus - from today's perspective - the special case of a genome mutation . (Autopolyploidie) was present) This finding was contrary to the on Charles Darwin subsequent theory of evolution , which the Presupposed occurrence of minor changes, and that was one of the reasons why “ Mendelism ” was at times in conflict with Darwinism , which was not yet generally accepted at the time .
In the years around the turn of the century, a number of researchers investigated the different forms of chromosomes and their behavior during cell division . On the basis of the observation that chromosomes appearing in the same way appear in pairs, Walter Sutton was the first to suggest in 1902 that this could have something to do with the likewise paired characteristics and their “splitting” in the studies by Mendel and his rediscoverers. Subsequently, Theodor Boveri formulated the chromosome theory of inheritance in 1904 , according to which the genetic makeup is bound to the chromosomes and their behavior during meiosis and fertilization corresponds to Mendel's rules.
A very momentous decision was the choice of fruit flies as a test object by the working group around Thomas Hunt Morgan in 1907, mainly because they can be kept in large numbers in a small space and reproduce much faster than the plants used until then. It soon became apparent that there are also minor mutations that allow gradual changes within populations (Morgan: For Darwin , 1909). Morgan's team made another important discovery around 1911, when the observation published by Correns as early as 1900 that some traits are usually inherited together ( gene coupling ) was combined with investigations into the chromosomes and thus came to the conclusion that the coupling groups were linked Groups of genes that are on the same chromosome. As it turned out, there can be an exchange of genes between homologous chromosomes ( crossing-over ), and based on the relative frequency of these intrachromosomal recombinations , a linear arrangement of the genes on a chromosome could be derived ( gene map ). Morgan summarized these findings in 1921 in The Physical Basis of Heredity and programmatically in 1926 in The Theory of the Gene , in which he further developed the chromosome theory into the gene theory.
This theory was very controversial even as it was gradually emerging. A central point of contention was the question of whether the genetic makeup is exclusively in the cell nucleus or also in the cytoplasm . Supporters of the latter view were u. a. Boveri, Correns, Hans Driesch , Jacques Loeb and Richard Goldschmidt . They postulated that in the core only relatively minor hereditary factors are localized up to species characteristics, while characteristics of higher systematic categories ( genus , family , etc.) are inherited through the plasma. The most determined representative of the opposing side was Morgan's former colleague Hermann Joseph Muller , who in The Gene as the Basis of Life (1929) described the genes located in the nucleus as the basis of life in general and classified the importance of plasma as secondary.
It was also Muller who first reported the generation of mutations by X-rays in 1927 , so that genetic research no longer had to wait for mutations to occur spontaneously. The view taken by de Vries, Morgan, Muller, and others of the randomness of mutations stood in the way. a. the postulate advocated by Paul Kammerer and Trofim Denissowitsch Lyssenko that mutations are "directed" and qualitatively determined by environmental influences.
After Mendel's mathematically exact description of dominant-recessive inheritance became generally known in 1900, the question was discussed whether recessive traits in natural populations gradually disappear or whether they remain in the long term. For this purpose, the German physician Wilhelm Weinberg and the British mathematician Godfrey Harold Hardy found a formula almost simultaneously in 1908 that describes the balance of dominant and recessive characteristics in populations. However, this discovery was initially hardly noticed by geneticists. It was not until 1917 that Reginald Punnett introduced what he called the “Hardy Law” into population research, which was an important contribution to the establishment of population genetics as an independent branch of research in the 1920s. Weinberg's contribution was only rediscovered in 1943 by Curt Stern , who then renamed the formula the “ Hardy-Weinberg Law ”.
The basics of population genetics were developed in parallel by Sewall Wright , Ronald A. Fisher, and JBS Haldane . They recognized that inheritance processes in nature should sensibly be considered at the population level, and formulated the theoretical bases for this (Haldane: A Mathematical Theory of Natural and Artificial Selection. 1924–1932; Fisher: The Genetical Theory of Natural Selection. 1930 ; Wright: Evolution in Mendelian Populations. 1931).
The genetic material
Since 1889 ( Richard Altmann ) it was known that chromosomes consist of “ nucleic acid ” and basic protein. For a long time, however, one could only speculate about their structure and function. In 1902 Emil Fischer and Franz Hofmeister postulated that proteins were polypeptides , i.e. long chains of amino acids . At that time, however, that was still very speculative. When the first analyzes of the amino acid composition of proteins were published in 1905, these only recorded a fifth of the protein examined, and the identification of all 20 proteinogenic amino acids took until 1935. In contrast, it was clear as early as 1903 ( Albrecht Kossel ) that nucleic acids contain only five different nucleic bases in addition to sugar and phosphate . First analyzes of the base composition by Hermann Steudel showed in 1906 that the four main bases present are contained in approximately equal proportions. Steudel (1907) concluded from this that the nucleic acid is “a relatively simply built body” that cannot be ascribed any demanding functions. This established itself as a doctrine that remained valid until the 1940s, and on this basis one did not consider the nucleic acid (s), but the proteins as "genetic material".
The insight that the reverse is true and that the nucleic acid DNA has to be regarded as a genetic material resulted from the experiments of Oswald Avery's group on the transformation of pneumococci (1944) and the Hershey Chase experiment of 1952 with bacteriophages . In addition, Erwin Chargaff showed in 1950 that the four nucleotides that make up the DNA are not contained in equal proportions , but rather in equal proportions in pairs . Together with X-ray structure analysis data from Rosalind Franklin , this formed the basis for the development of the double helix structure model of DNA by James Watson and Francis Crick in 1953.
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