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Transcript
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