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From

Darwin to Dolly
and Beyond
(1900-1950)

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Ibelgaufts From Darwin to Dolly and Beyond

1900
rediscovery of Mendels laws

Erich von Tschermak-Seysenegg


(Austrian botanist, geneticist; 1871-1962)

crosses with garden peas


independently rediscovered
laws of heredity developed
by Mendel

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Ibelgaufts From Darwin to Dolly and Beyond

1900-01
alleles reflect changes in genes

Hugo Marie de Vries


(Dutch botanist; 1848-1935)

independently rediscovered the laws of heredity


developed by Mendel
noticed unpredictable changes that had occurred in
primroses and brought the concept of mutations into
evolutionary theory and genetics
advanced the thesis that species are not continuously
connected but arise through sudden large changes

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Ibelgaufts From Darwin to Dolly and Beyond

1901
accessory chromosomes

Hermann Henking (German zoologist; 1858-1942)


C. E. McClung

Henking reported "a particular chromatin element"


(called X because function was unknown) in spermatozoa
of the fire bug
sees no relation to sex
McClung first to point out the relationship "sex
chromosome"

H. Henking, Z. Wiss. Zool., 5l (1890), quoted in C. E . McClung, 'The


Accessory Chromosome: Sex Determinant?"Biol. Bull, 3 (1902), 4384.

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Ibelgaufts From Darwin to Dolly and Beyond

1902
inborn errors of metabolism

Archibald E. Garrod
(British physician; 1857-1936)

first to apply Mendelian thinking to several inherited


human metabolic disorders
surmised that human diseases such as alkaptonuria were
the result of "inborn errors of metabolism" caused by
genetic defects
first recognition of a role for genetics in biochemistry
importance of this pioneering work was little
appreciated for several decades

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Ibelgaufts From Darwin to Dolly and Beyond

1902
Mendelian inheritance in poultry

William Bateson
(British biologist; 1861-1926)

Demonstrated for the first time that Mendel's rules also


apply to crosses with poultry

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Ibelgaufts From Darwin to Dolly and Beyond

1902
Mendelian inheritance in mice

Lucien Cunot (French zoologist; 1866-1951)


With Pierre Teilhard de Chardin

Confirmed that Mendel's rules also apply to crosses with


mice.

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Ibelgaufts From Darwin to Dolly and Beyond

1902
chromosome synapsis

Thomas Harrison Montgomery


(US zoologist; 1873-1912)

noticed the homologous pairing of maternal and paternal


chromosomes at synapsis prior to the reductive division

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Ibelgaufts From Darwin to Dolly and Beyond

1902/3
chromosome theory of heredity

Walter Stanborough Sutton


(US geneticist; 1876-1916)
Theodor Boveri
(German zoologist; 1862-1915)

Pointed out the interrelationships between cytology and


Mendelism
closes the gap between cell morphology and heredity

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Ibelgaufts From Darwin to Dolly and Beyond

1902/3
chromosome theory of heredity

Sutton observed chromosomal movements during


meiosis and homologous pairs of chromosomes in
grasshopper cells.
stated that chromosomes
are paired and may be the
carriers of heredity,
suggesting that Mendel's
"factors" are located on
chromosomes
egg and sperm cells receive only one chromosome from
each pair when they form during meiosis
this corroborated Mendel's theory that the genetic
"factors" are segregated
Boveri uses improved staining techniques and shows that
chromosomes are individual bodies
proves that each new cell has to receive a full set of these
threads for proper development
Sutton and Boveri propose that each egg or sperm cell
contains only one of each chromosome pair
chromosome theory connects two phemonema:
patterns by which pairs of Mendel's factors assort
themselves
precisely similar sorting and recombination of the
chromosomes in the formation of the germ cells and
the fertilization of the egg

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10

1903
Mendelian heredity in humans

William Ernest Castle


(US biologist; 1867-1962)

Studies albinism in blacks

second confirmation
(after Garrod) that Mendel's
laws also apply to humans

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Ibelgaufts From Darwin to Dolly and Beyond

11

1903
"BIOCHEMISTRY"

Carl Neuberg
(German biochemist; 1877-1956)

first used the term


biochemistry in his
inaugural lecture at the
university of Berlin

To say that a man is made up of


certain chemical elements is a
satisfactory description only for
those who intend to use him as
a fertilizer
Hermann Joseph Muller
Nobel prize for medicine 1946.

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Ibelgaufts From Darwin to Dolly and Beyond

12

1903
"Cytogenetics"

Walter Stanborough Sutton


(US geneticist; 1876-1916)

a field of investigation
incorporating genetics and cytology
concerned with the study of the behaviour of
chromosomes during mitosis and meiosis and their
relation to the transmission and recombination of
genes

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Ibelgaufts From Darwin to Dolly and Beyond

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1904 "Genetics";
Gene Linkage

William Bateson
(British biologist; 1861-1926)

demonstrates that some characteristics are not inherited


independently
This introduces the concept now called 'gene linkage'
Leads to the need for 'genetic maps' that describe the
order of the linked genes

coins a number of terms:


"allelomorphs" ("alleles") are Mendel's pairs of factors
(actually genes)
"heterozygote": the cell formed by the union of two
gametes, one recessive and one dominant
"homozygote":cells formed by similar gametes
In Bateson's inaugural address to the Third Conference on
Hybridization and Plant Breeding on July 31, 1906, he
suggested "...for the consideration of the Congress the
term 'genetics,' which sufficiently indicates that our
labours are devoted to the elucidation of the phenomena
of heredity and variation..
lists some 26 different cases of established
allelomorphism in wheat, maize, peas, snapdragon,
Datura, Oenothera, mouse, cattle, fowl, and man

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1905
"diploid", "haploid"

Eduard Strasburger
(German botanist; 1844-1912)

Diploid
cells and organisms containing two homologous
chromosome sets (one paternal, one maternal) with
the exception of sex chromosomes.
Haploid
single set of chromosomes

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Ibelgaufts From Darwin to Dolly and Beyond

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1906
Male Is XY, Female Is XX

Edmund Beecher Wilson (US zoologist; 1856-1939)


Nettie Maria Stevens (US zoologist; 1861-1912)

Independently described that XX chromosomes determine


female; XY determine male

Nettie Stevens correlated the presence of two specific X


chromosomes in 92 species of female insects while males
have only one X

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1906
Drosophila As Experimental Animal

William Ernest Castle (US biologist; 1867-1962)


Woodworth

introduced Drosophila as new experimental animal for


genetic studies.

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1907
sex is a Mendelian trait

Carl Erich Correns


(German botanist, geneticist;
1864-1933)

Independently rediscovered the laws of heredity


developed by Mendel
Demonstrated that sex is a simple Mendelian trait

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1909 "gene", "genotypes",


"phenotypes", "allele"

Wilhelm Johannsen
(Danish biologist; 1857-1927)

demonstrated that
natural selection cannot act on
genetically pure lines but can
only isolate existing genotypes.
natural selection can only
influence evolutionary
change if there is a source
of genetic variability

Johanssen left, Bateson right

Coined the terms


'gene' - carrier of heredity
'genotype' - genetic constitution of an organism
'phenotype' - caused by genotype and environmental
factors
allele - alternate form of a gene at the same
chromosome locus

Genetics: science studying transmission of traits


Embryology: science of the expression of those traits

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1909
chromosome chiasmata

F. A. Janssens (1863 - 1924)

suggested that the chiasmata observed between synaptic


chromosomes could be taken as observational evidence
for the phenomenon of crossing over among linked genes,
although he could not prove it

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1910/11
Drosophila Genetics, Recombination

Thomas Hunt Morgan (US geneticist; 1866-1945)


Nobel Prize 1933
Alfred Harry Sturtevant (US geneticist; 1891-1970)
Calvin Blackman Bridges (US geneticist; 1889-1938)
Hermann Joseph Muller (US geneticist; 1890-1967)

breeding experiments
cytological analyses

chromosomes behave very similarly to the ways in which


Mendel believed genes segregate and become randomly
assorted
genes for many character traits are arranged in a linear
fashion on each chromosome and created linear
chromosome maps in which each gene is assigned to a
specific position

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1910/11
Drosophila Genetics, Recombination

different linkage groups


alleles (pairs of genes affecting the same trait)
interchange, or cross over, in the same linkage group

separation of certain inherited characteristics that are


usually linked are caused by the breaking of
chromosomes sometimes during the process of cell
division

existence of sex-linked genes (eye color, body color,


wing shape, sex)

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1911
heterosis in maize, rice
G. H. Shull
"hybrid vigor"
heterozygous genotypes
are superior

heterosis, superiority or fitness has been measured


in different ways
increased total lifespan
increased rate of growth
greater average height or size at maturity
viability
reproductive fertility or fecundity
total yield

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Ibelgaufts From Darwin to Dolly and Beyond

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1912
polyploidy

A. M. Lutz

gigas mutation in the evening primrose contains twice the


usual chromosome number.
This led to the analysis and artificial production of
polyploidy.

REFERENCES: Lutz, AM Triploid mutants in Oenothera. Biologisches Centralblatt


32: 385 (1912)

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1913
enzyme kinetics

Leonard Michaelis (American chemist, 1875-1949)


Maud Leonora Menten (Canadian chemist, 1879-1960)

postulated the existence of an intermediate enzymesubstrate complex to explain the mechanism of enzyme
action

Michaelis is also the father of the home permanent, by


virtue of his discovery of the solubility of keratin in
thioglycolic acid)

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Ibelgaufts From Darwin to Dolly and Beyond

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1913
first genetic map

Alfred Harry Sturtevant


(US geneticist; 1891-1970)

constructed the first gene map by analyzing mating results


for fruit flies with six different mutant factors each known
to be recessive and X-linked
traced each mutation and its normal alternate in relation to
each of the other mutants, and thus calculated the exact
percentage of crossing-over between the genes

REFERENCES: Sturtevant AH and Morgan TH The


linear arrangement of six sex-linked factors in
Drosophila, as shown by their mode of association.
Journal of Experimental Zoology 14, 43-59.

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1920
genome

Hans Winkler (German botanist; 1877-1945)

Introduces the term to describe the haploid chromosome


set of an organism, i. e. the sum total of its genes

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1923
point mutations

Calvin Blackman Bridges


(US geneticist; 1889-1938)

A mutation which can recombine with any of a large


number of mutants (as opposed to deletions)
precise definition of a "point" depends on the number of
mutants crossed and on the smallest distance in the
genetic map. Today point mutation is a mutation in one
base pair

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1924
Feulgen stain

Robert Joachim Feulgen


(German physician; 1884-1955)

Developed a staining method for nucleic acids and its


microscopic detection

acidic Fuchsin solution; also called Acid magenta, Acid


rubin, Acid roseine, acid violet 19

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1927
first localization of mammalian gene

Theophilus Shickel Painter


American zoologist
(1889-1969)

Found a chromosome deficiency in mice which, along


with genetic evidence, provided the first case of localizing
a specific gene to a particular chromosome in mammals

Counted 48 human chromosomes


(number corrected in 1956 by Albert Levan and Joe-Hin
Tjio who perfected methods of preparing white blood
cells for chromosome analysis)

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1927
artificial transmutation of genes

Hermann Joseph Mller


(US geneticist; 1890-1967)
Nobel Prize 1946
Lewis J. Stadler

Mller discovered that X-rays induces genetic mutations


in fruit flies 1,500 times more quickly than under normal
circumstances
Stadler found that UV light induces mutations

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1928
Pneumococci transformation

Frederick Griffith
(British microbiologist; 1877-1941)

Proposed that some


unknown "principle" had
transformed the harmless
R strain of Diplococcus
to the virulent S strain

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1931
crossing-over in maize

Harriet B. Creighton
Barbara McClintock (US geneticist 1902-92) Nobel
Prize 1983

demonstrated a cytological proof for crossing over in


maize. A similar demonstration was made by Curt Stern
in Drosophila

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Ibelgaufts From Darwin to Dolly and Beyond

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1934
nucleus governs phenotype

Joachim Hmmerling

Acetabularia
single-celled algae
(2 cm)

grafting experiment
of parts containing
the nucleus show that
the control center of
development that
governs the phenotype
is located in the nucleus

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Ibelgaufts From Darwin to Dolly and Beyond

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1933
eugenics laws in Germany

Germany established eugenics laws


individuals sterilized as "hereditary defectives"

New eugenics and political


economy of the body

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1936
genes on giant chromosomes

Milisav Demerec (1895-1966)


Margaret E. Hoover

pointed out the correspondence between giant salivary


gland chromosome bands and gene maps.

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1938

Hans Adolf Krebs


(1900-1981)
Nobel Prize 1953

discovers the TCA cycle

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1941
one gene - one protein

Edward Lawrie Tatum (US geneticist; 1909-1975)


Nobel Prize 1958
George Wells Beadle (US geneticist; 1903 - 1989) Nobel
Prize 1958

investigated the transmission of hereditary characteristics


in bread mold genes
proved that particular genes are responsible for particular
enzymes and that therefore all biochemical processes are
regulated by genes

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Ibelgaufts From Darwin to Dolly and Beyond

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1943 genes have a physical reality


and jump

Barbara McClintock
(US geneticist 1902-92)
Nobel Prize 1983

noticed that certain genetic elements which did not have


fixed chromosomal location seemed to move about the
maize genome and inhibit the expression of other maize
genes with which they came into contact
developed the hypothesis of transposable elements to
explain color variations in corn
chromosome rearrangements correlate with redistribution
of specific genetic traits

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1944
DNA and genetic information

Oswald Avery (Canadian physician 1877-1955)


Colin Munro MacLeod (1909-1972)
MacLyn McCarty (1911-)

Isolation of Griffith' transforming principle and proof that


nucleic acids encode genetic information

REFERENCES: Avery, O.T., McLeod, C.M. & McCarthy M. Studies on


the chemical nature of the substance inducing transformation of
pneumococcal types. Induction of transformation by a desoxyribonucleic
acid fraction isolated from Pneumococcus Type III Journal of
Experimental Medicine 79, 137-158 (1944)

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1946
ENIAC

first digital vacuum tube computer in the world

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1946
chemical mutagenesis

Charlotte Auerbach (German-Scottish geneticist; 18991994)

demonstrates that nitrogen mustards can caus mutations in


cells.

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1946
gene transfer in E coli

Joshua Lederberg
(US geneticist; 1925-)
Nobel Prize 1958

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1949
molecular disease

Linus Carl Pauling (US biochemist; 1901-1994); Nobel


Prize 1954; 1962

Defining sickle cell anemia as a molecular disease


showed that sickle cell hemoglobin showed different
electrophoretic properties than normal hemoglobin. This
demonstrated that genetic mutations lead to specific
chemical changes in protein molecules

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1949-1950
protein sequencing

Frederick Sanger
(1918-)
Nobel Prize 1958, 1980

Pehr Victor Edman


(1916-1977)

Sanger developed the 2,4-dinitrofluorobenzine method

Edman developed the phenylisothiocyanate procedure for


identification of the N-terminal residues of peptides.

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1950
Chargaff rules

Erwin Chargaff
Austrian biochemist
(1905-2002)

in DNA amounts of A = T, G = C

"Chargaff's Rules" served as a key principle for Watson


and Crick in assessing various models for the structure of
DNA

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