Saturday, December 28, 2013

HISTORY OF GENETICS


The process of transmission of characters from onegeneration to next, either by gametes–sperms and ova–in sexual reproduction or by the asexual reproductive bodies in asexualreproduction, is called inheritance or heredity. Heredity is the cause of similarities between individuals. This is the reason that brothers and sisters with the same parents resemble each other and with their parents. Variation is the cause of differences between individuals. This is the reason that brothers and sisters
who do resemble each other are still unique individuals.
  • The biological science which deals with the mechanism of heredity and causes of variations in living beings (viruses, bacteria, plants and animals) is known as genetics. The word genetics was derived from the Greek root gen which means to become or to grow into and it wascoined by Bateson in 1906.
  • The ideas or theories which have been forwarded from time to time to explain the phenomenon of inheritance can be categorized under the following headings :
  • 1. Vapour and fluid theories; 2. Preformation theories;3. Particulate theories.
  • 1. Vapour and Fluid Theories
  • Early Greek philosophers such as Pythagoras (500 B.C.) proposed that every organ of animal bodygives out some type of vapours. These vapours unite and form a new individual.
  • Hippocrates (400 B.C.) believed that the reproductive material is handed over from all parts of the
  • body of an individual, so that the characters are directly handed over to the progeny.
  • Aristotle (350.B.C.) thought that the semen of man has some “vitalizing” effect and he considered it as the highly purified blood. According to him the mother furnishes inert matter and the father gives the motion to the new life.
  • 2. Preformation Theories
  • Leonardo da Vinci (1452–1519) proposed a theory that the male and the female parents contribute equally to the heredity of the offspring.
  • W. Harvey (1578–1657) speculated that all animals arise from eggs and that semen only plays vitalizing role.
  • R. de Graaf (1641–1673) observed that the progeny would have characteristics of father as well as of mother and, therefore, he proposed that both the parents should contribute to the heredity of progeny.
  • Malpighi (1673), the pioneer of preformationist school, concluded that development of any organism consisted simply of growth of preformed part.
  • A.V. Leeuwenhoek in 1677 observed sperms of several animals (man, dog, rabbit and other mammals, frog, fish and insects) and also suggested their association with eggs.
  • In 1679, J. Swammerdam studied development of insects and frog and suggested that development of an organism is a simple enlargement of a minute but preformed individual.
  • The figure of homunculus  or manikin, the miniature man in the sperm head, was published in 1695 by Hartsoeker.
  • Such type of theories which advanced the concept of the presence of preformed embryo in the sex cells are known as preformation theories.
  • Preformationists have, often, been divided into two schools: 1. Ovists who attached more importance
  • to ova; they thought that “homunculus” was present in the ovum.
  • 2. Animalculists or spermatists who attached more importance to sperm; they thought that a miniature but complete organism was present in the sperm.
  • N. Grew in 1682 reported for the first time the reproductive parts of plants.
  • R. Camerarius in 1694 described sexual reproduction in plants for the first time. He is also known to be first to produce a hybrid between two different plant species.
  •  In 1717, Fairchild produced a hybrid having characteristics of both parents. This hybrid was called “Fairchild’s Sweet William” or as “Fairchild’s mule.” This provides a means of artificial hybridization in plants.
  • J.G. Kolreuter (1733–1806) obtained fertile hybrids from artificial crosses between two species of tobacco plants.
  • K.F. Wolff (1738–1794) finally refuted the preformation theory by proposing that neither egg nor
  • sperm had a structure like homunculus but that the gametes contained undifferentiated living substance
  • capable of forming the organized body after fertilization. Such an idea formed the very core of the theory of epigenesis. This theory suggested that many new organs and tissues which were originally absent, develop subsequently. However, Wolff believed that these tissues and organs developed de novo due to mysterious vital forces.
  • 3. Particulate Theories
  • French biologist Maupertuis (1689–1759) has proposed that the body of each parent gives rise
  • minute particles. In sexual reproduction, the particles of both individuals unite together to form a new
  • individual. He thought that in certain cases the particles of the male parent might dominate on those
  • of the female parent and produce the male individual. In the production of female individual the particles female might dominate on particles of male. Thus, maupertuis proposed the concept of biparental inheritance by elementary particles. He studied the family pedigree of polydactyly and albinism in human beings.
  • The great biologist Lamarck (1744–1829) in 1809 proposed the phenomenon of “inheritance of
  • acquired characters” among living organisms. But he failed to provide convincing evidences in support
  • of his concepts.
  • In 1868 the well known naturalist Charles Darwin has given his famous theory of pangenesis
  • which exclusively depends on the particulate theory.
  • The central idea of pangenesis theory has been
  • given first of all by Hippocrates.
  • According to the pangenesis theory of Darwin each part of the animal body produces many minute particles known as gemmules. These gemmules are at first collected in the blood and later on are concentrated in the reproductive organs. When the animal reproduces into new individual, these gemmules pass on to it and it has blending of both parents. By this mechanism acquired
  • characters would also be inherited because as the parts of the body changed so did the pangenes or
  • gemmules they produced.
  • The theory of pangenesis was disapproved by Galton (1823–1911) and Weismann (1835–1934).
  • Weismann in 1892 postulated the theory of germplasm to explain heredity. According to this theory
  • the body of organisms contain two types of cells namely somatic cells and reproductive cells. The
  • somatic cells form the body and its various organ systems, while the reproductive cells form sperm and
  • ova. The somatic cells contain the somatoplasm and germinal or reproductive cells contain the
  • germplasm. According to Weismann the germplasm can form somatoplasm but somatoplasm cannot
  • form germplasm. Thus, the changes in the structure of somatic cells or somatoplasm which are caused
  • by the environment (acquired characters) cannot influence the reproductive cells or germplasm. By
  • cutting the tails of mice for many generations, Weismann always got tailed mice. So, by such experimental evidences he rejected the Lamarckism and pangenesis theory.
  • Augustinian Monk Gregor Mendel was the first investigator who laid the foundation of our modern concept of the particulate theory. He could understand the heredity problems more clearly than any one in the past, because his approach was simple, logical and scientific. By his famous experiments on pea plant he concluded that the inheritance is governed by certain factors which occur in the cells of each parent. He Gregor Mendel (1822-1884).thought that each parent has two such factors, while their sex cells (sperm or pollen and ovum or egg) have only one factor. However, he failed to explain the exact process by which these factors pass on the sex cells.
  • knight (1799) and Goss (1824) conducted hybridization experiments on edible pea (Pisum sativum), but they failed to formulate any law of inheritance like the Mendel.
  •  Von Baer (1828) made discovery of the mammalian egg. Pringsheim (1855) first saw nuclear fusion in green algae (Vaucheria). Heredity transmission through the sperm and egg became known by 1860. Ernst Haeckel, noting that sperm consisted largely of nuclear material, postulated that the nucleus is responsible for heredity.
  • Oscar Hertwig (1875) observed the entrance of the sperm into the sea urchin. He found nucleusto play an important role in hereditary mechanism. In 1884, Hertwig identified the hereditary substance with the chromatin of nucleus.
  • Strasburger in 1875 discovered the chromosomes and he along with Kolliker and Weismann formulated the nuclear theory of heredity.
  • Flemming (1882) investigated the process of mitosis.
  • Three plant breeders, namely Hugo de vries (Holland), Karl Correns (Germany) and Erich
  • Tschermak (Austria), rediscovered the Mendel's laws in 1900. Each of them reached similar conclusions before they knew of Mendel's work.
  • Bateson (1902) published a book “The Principles of Heredity.” From 1902 to 1909 he introduced the terms allelomorphs, homozygote, heterozygote, F1, F2 and epistatic gene. Bateson was the first to have Mendel's paper translated into English and the first to show that Mendel’s theory also applied to animals. He coined the term genetics in 1905.
  •  In 1906, Bateson and Punnett reported first case of linkage in sweet pea, however, they failed to explain the phenomenon of linkage correctly.
  • R.C. Punnett devised the Punnett’s square for making gametic combinations theoretically.
  • American cytologist, Walter S. Sutton in 1902 proposed the chromosome theory of heredity in his classic paper “The Chromosomes in Heredity,” in which he postulated that the newly rediscovered Mendel’s hereditary factors were physically located on chromosomes. This theory provided a mechanism of transmission to explain the behaviour of Mendel’s factors and brought together two independent desciplines– the genetics and the cytology. Thus, the year 1903 is the year
  • of birth of cytogenetics.
  • Archibald E. Garrod (1902) deciphered the inheritance pattern and metabolic nature of the human disease alkaptonuria (in which urine of patient turns dark to black upon exposure to air). In 1908, Garrod presented in a lecture nearly all the facts that we know today concerning this disease. He also
  • postulated various enzymes involved in this metabolic error, but he could not identify them.
  • In 1909 Johannsen formulated the genotype-phenotype concept to distinguish hereditary variations
  • from environmental variations. According to him, the genotype of an individual represents the sum total of heredity, while phenotype of an individual represents the observable structural and functional properties which are produced by the interaction between genotype and environment. (In 1877, Johannsen coined the term gene).
  • The hypothesis that “genes can change (mutate) to give rise to new genes (mutant genes)” was seriously tested, beginning in 1908 by American biologist Thomas H. Morgan andhis young collaborators (Ph.D. students), such as, Calvin B.Bridges, Hermann J. Muller and Alfred H. Sturtevant. They
  • worked on the fruit fly, Drosophila melanogaster. (W.E. Castle suggested the fruit fly to Morgan).
  •  In
  • 1910, first white eye mutant was detected in Drosophila by this team of workers and it is first reported
  • case of sex linkage.
  • T.H. Morgan (1866–1945) proposed in 1911 the theory of linkage. He turned the chromosometheory of inheritance into the concept of genes being located in a linear array on each chromosome. In
  • 1926, his book ‘The Theory of the Gene’ was published and he got Nobel prize in 1934.
  • Cytological basis of crossing over was first described by the Belgian cytologist F.A. Janssens in 1911. H.J. Muller and L.J. Stadler independently discovered that X-rays induce mutations. H.J. Muller got Nobel Prize in 1946 for the discovery of the induction of mutation in Drosophila by X-rays.
  • In 1916, Bridges made discovery of the phenomenon of non-disjunction in
  •  rosophila. In 1921, he proposed the genic balance mechanism of sex determination in Drosophila. B.O. Dodge in the late 1920’s and early 1930’s first determined the genetics of Neurospora.
  • T.M. Jenkins (1924) reported a case ofcytoplasmic inheritance, called Iojap striping in maize. Barbara McClintock and Harriet Creighton working at Cornell University, USA, with the corn plant, Zea mays,devised an elegant demonstration of chromosome breakage and rejoining during crossing over. In 1937,
  • Richard Goldschmidt stimulated exploratory questions on the chemical nature of gene (of Drosophila).
  • In the 1940’s, two significant discoveries were made concerning the chemical nature of the gene:
  • 1.Oswald Avery, C.M. MacLeod and M. McCarthy (1944) were able to establish by experiments with pneumonia-causing (virulent) bacteria that genes were composed of a specific type of nucleic acid, called deoxyribonucleic acid (DNA), and not proteins.
  •  2. While studying the biochemical basis for the eye colour in Drosophila, George Beadle and E.L. Tatum were able to show that the lack of brown colour in various mutants was due to a defect in one step in the biosynthesis of the brown pigment. They proposed the one-gene one-enzyme hypothesis which suggested that the action of each gene is through the synthesis of a protein (enzyme) which in turn catalyzes a single chemical reaction. They proved this hypothesis through the use of multitude of mutants in the fungus, Neurospora (in 1941). In most cases, each mutation was due to a change in a single gene. Thus, they initiated the branch of biochemical genetics.
  • The term molecular biology was first used in 1945 by William Astbury, who was referring to the study of the chemical and physical structure of biological macromolecules..
  • Joshua Laderberg (1946) first demonstrated the phenomenon of recombination in the bacteria E.coli. Beadle, Tatum and Laderberg got Noble prize in 1958.
  • Recombination in phage was first demonstrated in 1948 by Max Delbruck and Mary Delbruck.
  • The chemistry of DNA and RNA has been worked out by A. Kornberg and S. Ochoa ; both got Noble Prize in 1959.
  • In 1953, one of the mostsignificant twentieth-century discoveries in biology was made by James watson and Francis Crick.Their paper published in the British Journal Nature in which they proposed the molecular structure ofDNA, i.e., the molecular composition of the gene. Watson, Crick and Wilkins got Nobel Prize in 1962for the discovery of double helix model of DNA which opened the new vistas in the genetical world.
  • Seymour Benzer performed extensive investigations on the genetics of T4 bacteriophage of E. coli and in 1955,was able to define the gene in terms of function (cistron), recombination (recon)and mutation (muton) and to placean accurate molecular size estimate on the conceptual gene components.
  •  In 1961, Francois Jacob and Jacques Monod provided genetic evidence for a method of gene regulation in bacteria, now called the operon.
  •  In 1965, Jacob, Monod and Lwoff were awarded Nobel Prize for their contribution to microbial genetics. Gaulian and Kornberg isolated, purified and utilized DNA polymerase of E. coli.
  • R.W. Holley got Nobel Prize (1968) for the discovery of base sequence of tRNA. Holley died
  • in 1993. During 1961–1968, the genetic code of DNA was solved by M.W. Nirenberg, J.H. Matthaei, p.Leder,and H.G. Khorana.They synthesized small RNA molecules (mRNAs) of known composition and observed which amino acid was incorporated into protein in a cell-free protein synthesizing system. In 1968 Nirenbergand Khorana discovered the complicated DNA code known as genetic code. Both scientists along with Holly received the Nobel Prize in 1968.
  • N.L. Dhawan and R.L. Paliwal (1964) studied the cytoplasmic inheritance in maize.
  • The term transposons (i.e., jumping genes) is used in 1974 by R.W. Hedges and A.E. Jacob of Hammersmith Hospital in London, for a DNA segment or genetic element which could move from one molecule to another and carried resistance for antibiotic ampicillin in the bacterial cells. These transposons, however, were originally discovered in maize plant by Barbara McClintock by the name controlling elements in 1956.
  • During the late 1970’s, the science of genetics entered a new era dominated by the use of recombinant DNA technology or genetic engineering to produce novel life forms not found in nature. Through this technology, it has been possible to transfer genes from mammals into bacteria, causing the microbes to become tiny factories for making (in relatively large quantities) proteins of great economic significance such as hormones (insulin, growth hormones) and interferon (lymphocyte proteins that prevent replication of a wide variety of viruses). These proteins are produced in such small quantities in humans that the cost of their extraction and purification from tissues has been very expensive, thus, restricting their medical use in prophylaxis (prevention) and therapeutics (treatment) of disease. By genetic engineering, it has become possible to produce various blood clotting factors, complement proteins (part of the immune system) and other substance for the improvement of genetic deficiency diseases (euphenics) other current fields of genetic researchare oncogenes (cancer), antibody diversity (immunogenetics), homeotic mutation and behaviour.

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