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R E V I E W
GENETICSTHE SCIENTISTS
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Harvey
• William Harvey (1578–1657) wrote a treatise on reproduction and
development patterned after Aristotle’s work. He is credited with the
earliest statement of the theory of epigenesis, which posits that an
organism is derived from substances present in the egg that
differentiate into adult structures during embryonic development.
Epigenesis holds that structures such as body organs are not initially
present in the early embryo but instead are formed de novo (anew).
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Schleiden and Schwann
• Around 1830, Matthias Schleiden, and Theodor Schwann proposed
the cell theory, stating that all organisms are composed of basic units
called cells, which are derived from similar preexisting structures.
• The idea of spontaneous generation, the creation of living organisms
from nonliving components, was disproved by Louis Pasteur later in
the century, and living organisms were considered to be derived from
preexisting organisms and to consist of cells.
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Darwin
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Mendel
• Gregor Mendel• Proposed the existence of particulate unit factors (genes) are
passed from generation to generation
• Proposed four postulates of inheritance
• Unit factors (alleles of genes) exist in pairs (in diploid)
• If an organism has two different alleles (heterozygous) then one is dominant and the other is recessive. One expresses phenotype in heterozygote, and the other is hidden in heterozygote
• The paired unit factors segregate independently during gamete formation (meiosis).
• All possible combinations of gametes will form with equal frequency
• Proposed that traits assort independently during gamete formation.
• Used true breeding strains of peas with seven characteristics, each characteristic had two contrasting traits.
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Mendel
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Mendel
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Hardy and Weinburg• The relationship between the relative
proportions of alleles in the gene pool
and the frequencies of different
genotypes in a population was
described in the early 1900s in a
simple mathematical model
developed independently by the
British mathematician Godfrey H.
Hardy and the German physician
Wilhelm Weinberg.
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Hardy and Weinburg
• Given 36% of the population is blue eyed (recessive
phenotype)… what is p and q? p2, 2pq:
• Given that 36% is recessive then q2 = .36, therefore q = .6
• p + q = 1, therefore p = .4
• p2 = .16 and 2pq = .48
• To double check p2 + 2pq + q2 = 1
• .16 + .48 + .36 = 1
• Therefore dominant phenotype = 16%
Heterozygotes = 48%
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Hardy and Weinburg
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Luria and Delbruck
• In 1943, Salvador Luria and Max
Delbruck presented the first
direct evidence that mutations
do not occur as part of an
adaptive mechanism, but
instead take place
spontaneously and randomly.
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• In 1952, Norton Zinder and Joshua
Lederberg were investigating
possible recombination in the
bacterium Salmonella typhimurium.
What they discovered was a process
of bacterial recombination
mediated by bacteriophages and
now called transduction.
Lederberg and Zinder
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Griffith
• Frederick Griffith in 1927 showed that avirulent strains of Diplococcus pneumoniae could be transformed to virulence.
• He speculated that the transforming principle could be part of the polysaccharide capsule or some compound required for capsule synthesis.
• Proved there was a transforming principle.
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Avery, McLeod and McCarty
• The 1944 publication by
Oswald Avery, Colin
MacLeod, and Maclyn
McCarty concerning the
chemical nature of a
“transforming principle” in
bacteria was the initial
event leading to the
acceptance of DNA as the
genetic material.
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Hershey and Chase
• In 1952, Alfred Hershey and Martha
Chase using Escherichia coli and an
infecting virus (bacteriophage T2),
demonstrated DNA, and not protein,
is the genetic material.
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Chargaff
• The proportions change from species to species.
• Between 1949 and 1953, Erwin Chargaff and his colleagues used
chromatographic methods to separate the four bases in DNA samples
from various organisms. Quantitative methods were then used to
determine the amounts of the four bases from each source.
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Chargaff• Between 1949 and 1953, Erwin Chargaff and his colleagues used
chromatographic methods to separate the four bases in DNA samples
from various organisms. Quantitative methods were then used to
determine the amounts of the four bases from each source.
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Chargaff
Examples
• If A = 23% what is T, G and C?
• A = T; therefore T = 23%
• A + T + G + C = 100%; therefore 23 + 23 + G + C = 100%
• G + C = 54%
• G = C; therefore C = 27% and G = 27%
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Watson and Crick• In 1953, James Watson and Francis Crick proposed that the structure of
DNA is in the form of a double helix. The data available to Watson and
Crick, crucial to the development of their proposal, came primarily from
two sources: (1) base composition analysis of hydrolyzed samples of DNA
and (2) X-ray diffraction studies of DNA. Watson and Crick’s analytical
success can be attributed to their focus on building a model that
conformed to the existing data.
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Meselson and StahlMatthew Meselson and Franklin Stahl
• The Meselson-Stahl experiment demonstrated that:
• DNA replication is semiconservative
• Each new DNA molecule consists of one old strand and one
newly synthesized strand.
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Meselson and Stahl
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Taylor, Woods, and Hughes
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Ames• In 1974, Bruce Ames developed a simple test for
evaluating the potential of chemicals to cause
cancer. The Ames test is based on the principle
that both cancer and mutations result from
damage to DNA, and the results of experiments
have demonstrated that 90% of known
carcinogens are also mutagens. Ames proposed
that mutagenesis in bacteria could serve as an
indicator of carcinogenesis in humans.
• A bacterial assay developed by Bruce Ames to
detect mutagenic compounds; it assesses
reversion to histidine independence in the
bacterium Salmonella typhimurium.
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Ames
• Ames test• The Ames test uses a number of different
strains of Salmonella typhimurium selected
for their ability to reveal the presence of
specific types of mutations
• The Ames test is used extensively during
the development of industrial and
pharmaceutical chemical compounds
• Many known carcinogens have been
shown by the Ames test to be strong
mutagens.
• More than 60 compounds found in
cigarette smoke test positive in the
Ames test and cause cancer in animals.
• Note this is a first step, not proof of
carcinogen.
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Nirenberg and Matthaei• Nirenberg and Matthaei
• Cracked the genetic code by using nucleic acid homopolymers to translate specific amino acids.
• Added RNA homopolymers to the in vitro translation system to decipher which amino acids were encoded by the first few codons based on which amino acids were incorporated into the polypeptide.
• In 1961, Marshall Nirenberg and J. Heinrich Matthaei became the first to characterize specific coding sequences, laying a cornerstone for the complete analysis of the genetic code. Their success, as well as that of others who made important contributions in deciphering the code, was dependent on the use of two experimental tools, an in vitro (cell-free in a test tube) protein-synthesizing system and the enzyme polynucleotide phosphorylase, which allowed the production of synthetic mRNAs. These mRNAs served as templates for polypeptide synthesis in the cell-free system.
• RNA homopolymers• RNA nucleotides with only one type of ribonucleoside
• RNA heteropolymers• RNA nucleotides with two or more different ribonucleosides
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• Nirenberg and Leder• Developed the triplet binding assay to determine other specific codon
assignments.• In 1964, Nirenberg and Philip Leder developed the triplet binding assay,
leading to specific assignments of triplet codons. • Triplet binding essay
• In this technique ribosomes bind to a single codon of three nucleotides and the complementary amino acid charged tRNA will be able to bind.
• This technique took advantage of the observation that ribosomes, when presented in vitro with an RNA sequence as short as three ribonucleotides, will bind to it and form a complex similar to what is found in vivo. The triplet RNA sequence acts like a codon in mRNA, attracting a tRNA molecule containing a complementary sequence. Such a triplet sequence in tRNA, that is, complementary to a codon of mRNA, is known as an anticodon.
Nirenberg and Leder
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Crick• Wobble hypothesis
• Predicts that the initial two ribonucleotides of triplet codes are often more critical than the third. The third position of the codon-anticodon interaction would be less spatially constrained and need not adhere as strictly to the established base-pairing rules at the third position of the codon.
• An idea proposed by Francis Crick, stating that the third base in an anticodon can align in several ways to allow it to recognize more than one base in the codons of mRNA.
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Holley• In 1965, Robert Holley and his colleagues
reported the complete sequence of tRNAAla
isolated from yeast. Of great interest was their finding that a number of nucleotides are unique to tRNA, each containing a so-called modified base.
• These modified structures are created after transcription of tRNA, illustrating the more general concept of posttranscriptional modification.
• Holley’s sequence analysis led him to propose the two-dimensional cloverleaf model of tRNA. It had been known that tRNA has a characteristic secondary structure created by base pairing. Holley discovered that he could arrange the linear sequence in such a way that several stretches of base pairing would result.
His arrangement, with its series of paired stems and unpaired loops, resembled the shape of a cloverleaf.
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Beadle and Tatum
• Beadle and Tatum
• Beadle and Tatum (1940’s)
showed that nutritional
mutations in the bread mold
Neurospora caused the loss of
an enzymatic activity that
catalyzes an essential reaction in
wild-type organisms
• One gene one enzyme
hypothesis.
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Jacob and Monod• Jacob and Monod
• In 1961, François Jacob and Jacques Monod described the “operon model” for the genetic control of lactose metabolism in E. coli. This work and subsequent research on the genetics of lactose metabolism established the operon as the basic unit of transcriptional control in bacteria. Despite the fact that, at the time, no methods were available for determining nucleotide sequences, Jacob and Monod deduced the structure of the operon genetically by analyzing the interactions of mutations that interfered with the normal regulation of lactose metabolism.
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Prepared and Compiled from various sources by D. Leonard (Learning Specialist)The Academic Support Center @ Daytona State Collegehttp://www.daytonastate.edu/asc/ascsciencehandouts.html
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