Download Molecular Biology - Intro

Molecular Biology
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Introduction
– Definitions
– History
– Central Dogma
Molecular Biology
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Definitions
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Chromosomes
DNA
Gene
Genotype
Phenotype
Molecular Biology
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Chromosomes
– The structure in cells that carries hereditary
information
– Composed of DNA and protein
– Prokaryotic - circular
– Eukaryotic - linear
Molecular Biology
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DNA
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Nitrogenous base (4 bases - A,T,G & C
Deoxyribose sugar
Phosphate
Nitrogenous bases are paired
» AT
» GC
– Double helix structure
Molecular Biology
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Genes
– Segments of DNA
– Functional or regulatory
– Mutability and variation
Molecular Biology
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Genotype
– The genetic make-up of an organism; the
information that codes for all the
characteristics of an organism
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Phenotype
– The expression or physical manifestation of
a gene; how it appears
Molecular Biology
Molecular biology seeks to understand
the molecular or chemical basis of
genetics
 History of molecular biology is a
melding of biochemistry, especially
nucleic acid biochemistry and genetics
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Molecular Biology
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Biochemistry
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Meischer
Avery & MacLeod
Hershey & Chase
Watson & Crick
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Genetics
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Mendel
Sutton
Morgan
Griffith
Delbruck
Beadle & Tatum
Tatum & Lederberg
Molecular Biology - Genetics
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Mendel (1865)
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Fluid vs. particulate inheritance
Studied pure breeding pea plants
Law of Segregation
Law of Independent Assortment
Rediscovered by de Vries & others
Molecular Biology
Molecular Biology
Molecular Biology - Genetics
Cross of pure breeding purple flowers with
pure breeding white flowers produces all purple
plants with genotype Pp; crossing Pp plants
produces following distribution:
P
p
P
PP
purple
Pp
purple
p
Pp
purple
pp
white
Molecular Biology - Genetics
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Walter Sutton (1902)
– Studied meiosis in grasshoppers (insects
have large readily observable
chomosomes)
– Observed that chromosomes behave in
manner similar to segregation of hereditary
material
– Found that chromosomes occur in
morphologically similar pairs
– Pairs separate during meiosis
Molecular Biology - Genetics
Molecular Biology - Genetics
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Morgan
– Developed modern science of genetics
– Used fruit flies because they had a shorter
generation time than peas
– Discovered sex-linkage
– Students developed techniques of mapping
genes on chromosomes
Molecular Biology - Genetics
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Griffith
– discovered transformation in 1927
– is a means of genetic transfer in
microorganisms
– a process by which a nonpathogenic strain
is transformed into a pathogenic strain
Molecular Biology - Genetics
Molecular Biology - Genetics
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Delbruck
– developed quantitative methods for
analysis of bacteriophage; viruses of
bacteria
– organized course to teach biologists
methods at Cold Spring Harbor resulting
in a large number of biologists trained in
molecular techniques
Molecular Biology - Genetics
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Beadle & Tatum
– developed Neurospora as an experimental
organism
– established one gene one enzyme
hypothesis
– generation time is even shorter with
Neurospora
Molecular Biology - Genetics
Molecular Biology - Genetics
Molecular Biology - Genetics
Molecular Biology - Genetics
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Tatum & Lederburg
– discovered conjugation in bacteria
– Led to genetic map of E. coli
– E. coli became widely used in molecular
biology
Molecular Biology - Biochemistry
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Meischer (1869)
– Austrian doctor
– isolated a substance called “nuclein” from
the nuclei of cells obtained from the pus of
surgical bandages
– found to contain nitrogenous chemicals,
sugar and phosphate
Molecular Biology - Biochemistry
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Avery & MacLeod (1944)
– isolated Griffith’s transforming factor to a
high degree of purity
– characterized transforming factor using
highly purified enzymes
– found transforming factor to be DNA
Molecular Biology
Substance Enzyme
Transform
Capsule
Carbohydrase Yes
Protein
Protease
Yes
RNA
RNAse
Yes
DNA
DNAse
No
Molecular Biology - Biochemistry
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Hershey & Chase (1952)
– used newly developed radioisotopes
» 35S for protein
» 32P for nucleic acid
– labeled bacteriophage (a virus of bacteria)
– found 32P went into cells but 35S did not
implying that nucleic acid transfer
information to cell for new bacteriophages
Molecular Biology - Biochemistry
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Watson & Crick (1953)
– used X-ray crystallography to study
structure of DNA
– by combining chemical data and X-ray
data were able to construct a model of
DNA
– structure inferred function leading to
Central Dogma