Breve História da Genética Fontes: 2002/2003 Genetics in context ( www.esp.org) Nobel Organization (www.nobel.se) A History of genetics (A.H.Wturtevant) Prof.Doutor José Cabeda Genética Timeline 2,000 bc 2400bc 1 1,000 2,000 400bc Hipocrates Aristoteles 1600 1700 1800 2000 Genética Molecular Período Pré - Mendel Genética das populações 1809 – Lamarck 1819 – Herbert 1820 - Nasse 1827 – Lecoq 1823 - Amici 1839 – Gärtner 1853 - Thuret 1855 – Naudin 1855 - Mendel 1856 – Pringsheim 1861 - deBari 1865 - Wichura 1868 – Darwin 1866-1900 1676 - Nehemiah Grew 1677 - Leeuwenhoek 1744 – Maupertuis 1691 - Camerarius 1760 – Lineu 1761 – Kölreuter 1779 –M. Lout 1900 Idade Antiga <2400 bc 400bc Hipocrato (470-370bc) Teoria da pangenese (cada parte do corpo produz algo que é colhido no semen e que é a essência da hereditariedade Aristóteles (384-322 bc) Critica a teoria da pangenese: Hereditariedade de caracteres de antecedentes que não os pais Hereditariedade de peculiaridades de unhas,cabelos e hábitos Hereditariedade de características tardias (tipo de barba, cabelo grisalho, etc) Ausência de efeito hereditário das mutilações Timeline Periodo Pré-Mendel (I) 1676 Nehemiah Grew Generalização que as plantas tem reprodução sexuada e que o polen é o elemento masculino 1691-1694 Camerarius Base experimental da generalização de Grew 1760 Lineu Empresta a sua reputação à generalização de Grew, estabelecendo definitivamente a questão de forma universalmente aceite 1677 Leuwenhoek Observa ao microscópio espermatozoides animais e enuncia o principio que apenas um é necessário para a fertilização. Este principio demoraria um século a estabelecer-se de modo universal O conceito do Homunculus ou dos animalcules Spermatozoïd with a fetus (N.Hartsoeker 1694) Periodo Pré-Mendel (II) 1744 Maupertuis Publica “Human pedigrees with poludactylism” e discutiu o albinismo 1761-67 J.G.Kolreuter Crosses between species of Nicotiana. Concludes that each parent contributes equally. Afirma que mais que um grão de polen é necessário para a fertilização. Os seus estudos foram feitos em água, o que lisou os tecidos, levando-o a afrimar que o fluido era responsável pela fertilização. 1779 M.Lout Reports the peculiar inheritance of Human Color Blindness 1794 Erasmus Darwin (Charles’ Grandfather) Publishes “zoonomia” or the laws of the organic life 1809 Jean B. Lamarck Presents “Theory of evolution” on his book “Philosophie Zoologique” Birth of Charles Darwin 1820 Christian F. Nasse Nasse’ law: Hemophilia occurs only in males but is transmited by unaffected females 1822-24 Knight, Goss, Seton Perform crosses with peas. Observe dominance. No numerical studies performed Thomas Andrew Knight confirmed reports of dominance, recessivity, and segregation in peas, but did not detect regularities 1831 Robert Brown published his observations reporting the discovery and widespread occurrence of nuclei in cells Periodo Pré-Mendel (III) 1831-36 Charles Darwin Darwin sails as naturalist aboard the voyage of the HMS Beagle. 1840 Martin Barry expressed the belief that the spermatozoon enters the egg. 1844 Charles Darwin Darwin first outlines his thoughts on natural selection in an unpublished essay. Chambers Chambers publishes (anonymously) his Vestiges of the Natural History of Creation Alfred R.Wallace publishes "On the Law which has Regulated the Introduction of New Species," anticipating Darwin's theory of evolution by natural selection. Rudolf Virchow states the principle that new cells come into being only by division of previously existing cells: "Omnis cellula e cellula." Luis Pasteur Louis Pasteur refutes the doctrine of spontaneous generation. 1855 1864 Timeline Mendel 1865 Mendel presents his work on peas to the Brünn Natural History Society. The results are published the following year. 1866 Mendel Gregor Mendel publishes his findings on heredity in peas, in Versuche über Pflanzen Hybriden. Summary of Mendel's Results: •The F1 offspring showed only one of the two parental traits, and always the same trait. •Results were always the same regardless of which parent donated the pollen (was male). •The trait not shown in the F1 reappeared in the F2 in about 25% of the offspring. •Traits remained unchanged when passed to offspring: they did not blend in any offspring but behaved as separate units. •Reciprocal crosses showed each parent made an equal contribution to the offspring. Mendel's Conclusions: •Evidence indicated factors could be hidden or unexpressed, these are the recessive traits. •The term phenotype refers to the outward appearance of a trait, while the term genotype is used for the genetic makeup of an organism. •Male and female contributed equally to the offsprings' genetic makeup: therefore the number of traits was probably two (the simplest solution). •Upper case letters are traditionally used to denote dominant traits, lower case letters for recessives. Timeline 1866-1900 (I) 1868 Darwin Darwin publishes Variation in Animals and Plants., relatando experiências de várias fontes. Descreve 2 tipos de cruzamentos: continuos e descontínuos (dominantes e recessivos) deduzindo que o cruzamento leva á homogeneização e o “inbred” á diferenciação. A sua teoria da hereditariedade foi pouco aceite mas preparou o caminho para Weissman e de Vries que em 1900 redescobre Mendel. 1869 F. Galton publishes Hereditary Genius. In it he describes a scientific study of human pedigrees from which he concludes that intelligence has a genetic basis. 1871 Johann Friedrich Miescher Isolated a substance which he calls NUCLEIN from the nuclei of white blood cells that was soluble in alkalis but not in acids. This substance came to be known as nucleic acid. Charles Darwin's Publication of Descent of Man, in which the role of sexual selection in evolution is described for the first time. Anton Schneider observed and described the behavior of nuclear filaments (chromosomes) during cell division in his study of the platyhelminth Mesostoma. His account was the first accurate description of the process of mitosis in animal cells. 1873 1866-1900 (I) F. Galton demonstrates the usefulness of twin studies for elucidating the relative influence of nature (heredity) and nurture (environment) upon behavioral traits. Oscar Hertwig Concludes from a study of the reproduction of the sea urchin that fertilization in both animals and plants consists of the physical union of the two nuclei contributed by the male and female parents. E.Strasburger accurately described the processes of mitotic cell division in plants. 1879-82 W. Flemming describes and names CHROMATIN, MITOSIS, and the SPIREME. He makes the first accurate counts of chromosome numbers and accurately drew the "longitudinal splitting" of chromosomes. 1883 E. Beneden announced the principles of genetic continuity of chromosomes and reported the occurrence of chromosome reduction at germ cell formation. The sperm and egg are haploid and fertilization restores the diploid chromosome number. A. Weismann points out the distinction in animals between the somatic cell line and the germ cells, stressing that only changes in germ cells are transmitted to further generations. 1875 1866-1900 (I) 1884-88 O. Hertwig, E. Strasburger, A. Kölliker, A. Weismann. Simultaneous identification of the cell nucleus as the basis for inheritance was independently reported by 1885 Walther Flemming observed sister chromatids passing to opposite poles of the cell during mitosis. 1889 Francis Galton publishes Natural Inheritance. In it he describes the quantitative measurement of metric traits in populations. He thus founds biometry and the statistical study of variation. Ultimately, he formulates the Law of Ancestral Inheritance, a statistical description of the relative contributions to heredity made by one's ancestors. 1896 E. B. Wilson publishes The Cell in Development and Heredity. This influential treatise (ultimately reprinted in several editions) distills the information compliled concerning cytology in the half-century since Schleiden and Schwann put forth the cell theory. The First International Congress of Genetics held in London. 1899 Timeline Richard Altmann renamed "nuclein" NUCLEIC ACID. William Bateson writes a paper on hybridisation and cross-breeding as a method of scientific investigation that anticipates Mendel's rediscovery. A Redescoberta 1900 H. de Vries, C. Correns, E. Tschermak independently rediscover Mendel's paper. Using several plant species, de Vries and Correns had performed breeding experiments that paralleled Mendel's earlier studies and had independently arrived at similar interpretations of their results. 40 reprints: 38 ?; 1 para kerner (não aberto); 1 para Nägelli que não o compreendeu/apreciou 120 cópias trocadas com bibliotecas originaram 4 citações: (Hoffman 1869; Focke 1881 did not understand but mentioned the arrival at constant numerical quantities; Baylei 1895 (copia da ref. de Focke) Enciclopedia britanica 1881-1895 De vries leu a ref de Bailey e desta chegou ao artigo original, que citou várias vezes em 1900, como suporte ao seu próprio trabalho. A Genética de Populações (I) 1901 H. de Vries adopts the term MUTATION to describe sudden, spontaneous, drastic alterations in the hereditary material of Oenothera. 1903 W.L.Johannsen. The concepts of PHENOTYPE, GENOTYPE, and SELECTION were introduced and clearly defined 1906 W. Bateson and R.C. Punnett reported the discovery of two new genetic principles: LINKAGE and GENE INTERACTION. 1908 G.H. Hardy writes a letter to the editor of Science, suggesting that Mendelian mechanisms acting alone have no effect on allele frequencies. This observation forms the mathematical basis for population genetics. 1909 T. H. Morgan (later to become the first recipient of the Nobel Prize for work in genetics) writes a paper expressing doubts about the profusion of Mendelian explanations for inherited properties. publishes Inborn Errors of Metabolism, the earliest discussion of the biochemical genetics of man (or any other species). puts forward the multiple-factor hypothesis to explain the quantitative inheritance of seed-coat color in wheat A. E. Garrod H. Nilsson Ehle A Genética de Populações (II) 1910 T. H. Morgan discovers white eye and consequently sex linkage in Drosophila. Drosophila genetics begins. 1913 A. H. Sturtevant provides the experimental basis for the linkage concept in Drosophila and produces the first GENETIC MAP. 1923 C. B. Bridges discovers chromosomal translocations in Drosophila. 1926 A. H. Sturtevant finds the first inversion in Drosophila. F. Griffith discovers type-transformation of pneurnococci. This lays the foundation for the work of Avery, MacLeod, and McCarthy (1944). 1931 C. Stern, H. B. Creighton B. McClintock independently, provide the cytological proof of crossing over. 1933 T. H. Morgan receives a Nobel Prize in Medicine for his development of the theory of the gene. He is the first geneticist to receive this award 1937 T. Dobzhansky publishes Genetics and the Origin of Species. A milestone in evolutionary genetics. 1941 G. W. Beadle E. L. Tatum publish their classic study on the biochemical genetics of Neurospora and promulgate the ONE-GENE, ONEENZYME theory. Timeline A Genética Molecular (I) 1944 O. T. Avery C. M. MacLeod M. McCarty Macklyn McCarty describe the pneumococcus transforming principle. The fact that it is rich in DNA suggests that DNA and not protein is the hereditary chemical. A Genética Molecular (II) 1946 H. J. Muller Nobel Prize in Medicine for his contributions to radiation genetics 1950 E. Chargaff lays the foundations for nucleic acid structural studies by his analytical work. He demonstrates for DNA that the numbers of adenine and thymine groups are always equal and so are the numbers of guanine and cytosine groups. These findings later suggest to Watson and Crick that DNA consists of two polynucleotide strands joined by hydrogen bonding between A and T and between G and C. 1952 Hershey and Chase Publicam uma experiência com Fagos T2 cujo DNA era radioactivo, demonstrando que também nos virus os ácidos nucleicos eram os determinantes da hereditariedade A Genética Molecular (III) A Genética Molecular (IV) J. D. Watson F. H. C. Crick propose a model for DNA comprised of two helically intertwined chains tied together by hydrogen bonds between the purines and pyrimidines. Rosalind Franklin Produziu as imagens de cristalogafia de raio X utilizadas por Watson e Crick. Independentemente chega a um modelo muito próximo do de destes M.Wilkins Descreve a estrutura B do DNA 1957 V. M. Ingram reports that normal and sickle-cell hemoglobin differ by a single amino acid substitution. 1958 F. H. C. Crick suggests that during protein formation the amino acid is carried to the template by an adaptor molecule containing nucleotides and that the adaptor is the part that actually fits on the RNA template. Crick thus predicts the discovery of transfer RNA 1953 A Genética Molecular (V) 1958 M. Meselson and F. W. Stahl George W.Beadle, Edward L. Tatum, Joshua Lederberg use the density gradient equilibrium centrifugation technique to demonstrate the semiconservative distribution of density label during DNA replication in E. coli. share a Nobel Prize in Medicine for Beadle and Tatum's discovery that genes act by regulating definite chemical events, and for Lederberg's discoveries concerning genetic recombination and the organization of the genetic material of bacteria. 1961 F. Jacob and J. Monod publish "Genetic regulatory mechanisms in the synthesis of proteins," a paper in which the theory of the OPERON is developed 1962 Watson, Crick, and Wilkins share a Nobel Prize in Medicine for their work in elucidating the structure of DNA. watson Crick wilkins A Genética Molecular (VI) 1968 Robert W. Holley, Har G. Khorana, M. W. Nirenberg Holley 1969 Khorana Max Delbrück, Alfred D. Hershey, Salvador E. Luria Delbrück Hershey share a Nobel Prize in Medicine for their interpretation of the genetic code and its function in protein synthesis. Nirenberg share a Nobel Prize in Medicine for their discoveries concerning the replication mechanism and the genetic structure of viruses. Luria A Genética Molecular (VII) 1980 P.Berg 1983 Paul Berg, Walter Gilbert, Frederick Sanger w.Gilbert Barbara McClintock share a Nobel Prize in Chemistry, with Berg cited for for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinantDNA, and Gilbert and Sanger cited for their contributions concerning the determination of base sequences in nucleic acids. This is Sanger's second Nobel, the first having come in 1958 for his work on the structure of insulin. F.Sanger receives the Nobel Prize in Medicine for her discovery of mobile genetic elements. A Genética Molecular (VIII) 1993 R. J. Roberts, and Phillip A. Sharp share a Nobel Prize in Medicine for for their discoveries of split genes. Kary Mullis and Michael Smith share a Nobel Prize in Chemistry, with Mullis cited for his contributions to the developments of methods within DNA-based chemistry and Smith for his fundamental contributions to the establishment of oligonucleotide-based, site-directed mutagenesis and its development for protein studies. K.Mullis M.Smith Stephen Baylin Metilação do Gene de Supressão Tumoral p16 numa variedade de tumores humanos Tratamento destas células com agentes desmetilantes repõe a actividade do gene A Genética Molecular (IX) 1995 Edward B. Lewis C.Nüsslein-Volhard Eric F. Wieschaus E.Lewis M.Smith E.Wieschaus Clonagem do primeiro mamifero (Dolly) por transferência de núcleo de célula somática 1997 1998 Share a Nobel Prize in Medicine for their discoveries concerning the genetic control of early embryonic development Adrian Bird Mostrou que as desacetilases podem funcionar em conjunto com metilases: se a desacetilase for inibida, a metilação não inactiva os genes Sequenciação do genoma Humano terminada na sua primeira versão 2001 Tony Kouzarias Metilação de histonas desliga os genes A Genética Molecular (X) Morte de Dolly reforça preocupação com o envelhecimento prematuro dos clones animais por transferência de nucleos de células somáticas 2003 Sydney Brenner H. Robert Horvitz John E. Sulston S.Brenner Horvitz Shared a Nobel Prize in Medicine for their discoveries concerning genetic regulation of organ development and programmed cell death Sulston