Download Introduction to Molecular Genetics

Genetics: Definitions & Disciplines
Introduction to
Molecular Genetics
„ Genetics: the science of variation and hereditary
„ Disciplines:
¾ What living organism are you studying?
8 Plant, bacterial, human, & medical genetics
¾ What area are you working on?
8 Molecular genetics
8 Cytogenetics
8 Biochemical genetics
8 Population genetics
8 Developmental genetics
8 Clinical genetics
8 ..
Mohammad Keramatipour MD
MD, PhD
Keramatipour@tums ac ir
[email protected]
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Molecular Biology?
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Historical Developments
„ What is molecular biology?
„ Pangenesis theory of inheritance: 400 B.C., by
Hippocrates
„ Homunculus (little man) theory, spermists / Ovists (17
(17th)
th)
„ Blending theory of inheritance
„ Mendelian inheritance (particulate theory of inheritance)
„ Era of modern genetics
¾ Science of understanding biological phenomena in
molecular terms
¾ The study
y of gene
g
structure and function at the molecular
level
„ It grew out of genetics and biochemistry
¾ Chromosome theory of inheritance
¾ Molecular genetics
„ Wide area of overlap between molecular biology and
¾ Recombinant DNA technology
molecular genetics
¾ Genomics
¾ Post
Post--genomics era
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Time Line of the Field
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Nobels in Medicine & Physiology
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More of Nobel Laureates
Nobel Laureates
„ 2000
2000:: Arvid Carlsson,
Carlsson, Paul Greengard,
Greengard, Eric R Kandel
Tim Hunt
2001
„ 2001
2001:: Leland
L l dHH
Hartwell,
t ll Ti
Tim H
Hunt,
t Si
Sir P
Paull N
Nurse
„ 2002
2002:: Sydney Brenner, H Robert Horvits
Horvits,, John E Sulston
Sydney Brenner
2002
John Sulston
2002
Martin Evans
2007
„ 2003
2003:: paul C Lauterbur,
Lauterbur, Sir Peter Mansfield
„ 2004
2004:: Richard Axel, Linda B Buck
„ 2005
2005:: Barry J Marshall, Robin Warren
„ 2006
2006:: Andrew Z Fire, Craig C Mello
„ 2007
2007:: Mario R Capecchi
Capecchi,, Sir Martin Evans, Oliver
Smithies
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Australia - 2003
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Australia - 2003
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Transmission Genetics
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Mendel’s Experiments
„ Gregor Mendel (1822
(1822--1884
1884))
„ A monohybrid cross
¾ Working on pea plants
8 True
True--breeding line for seven traits
8 Monohybrid
y
& dihybrid
y
crosses
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Interpretation of Data
A Dihybrid Cross
„ Results:
„ Guess different possibilities:
¾ Particulate theory of
¾ Linked assortment
inheritance
¾ Dominant &
recessive
¾ Mendel’s law of
segregation
¾ Independent assortment
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A Dihybrid Cross
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Rediscovery of Mendel’s Laws
„ Rrsults
Rrsults::
„ Boveri and Sutton – 1902/3
¾ Non
Non--p
parental offspring:
p g No
¾ The chromosome theory
y of inheritance
linked assortment
¾ Phenotype ratio in F2
F2
generation: 9:3:3:1
¾ Law of independent
assortment
¾ New concepts: chromosome, locus, diploid, haploid,
homozygous, heterozygous
„ Thomas Hunt Morgan – 1910
¾ Experiments on Drosophila
¾ Concepts introduced
8 Sex
Sex--linked traits, autosomes & sex chromosomes, wildwild-type,
mutant
8 Genetic linkage,
linkage recombination,
recombination recombinant offspring
offspring,
genetic mapping, centimorgan
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The Era of Molecular Genetics
Understanding Genes
¾ Which sort of structure genes have?
8 1953
1953:: the discovery of DNA structure
„ Understanding genes and their structure?
¾ The chromosome theory of inheritance
8 Genes on chromosomes, in nucleus
„ Activities of genes
¾ Chemical nature of DNA, RNA
8 1869
1869:: Friedrich Miescher discovered ‘‘nuclein
nuclein’’
8 End of nineteenth century: chemical nature of DNA
¾ Relationship between genes and proteins
¾ Gene expression
¾ Gene mutations
¾ Ge
Gene
e ccloning
o g
¾ What is the composition of genes?
8 Protein, DNA, or RNA?
8 1944
1944:: Oswald Avery & colleagues showed that genes
composed of DNA
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Nucleic Acids
Nucleic Acids
- Nucleic Acids: A group of macromolecules that:
a. have acidic properties
b located
b.
l
t d iin th
the nucleus
l
c. are polymers of nucleotides
- Nitrogenous bases: There are two groups of nitrogenous bases:
a Purine: A & G
a.
b. Pyrimidine: T, C, & U
- Required for the storage and expression of genetic information
- Sugar:
- Deoxyribose in DNA
- Ribose in RNA
- There are two classes of nucleic acid:
a. Deoxyribonucleic acid (DNA)
b. Ribonucleic acid (RNA)
- Sugar and phosphate make the backbone of DNA and
nitrogenous bases carry the genetic information
- Nucleotide: A nucleotide consists of three parts:
a. A nitrogenous base
b. A sugar
c. One or more phosphate group
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The Components of Nucleotides
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The Structure of Nucleotides
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DNA & RNA Strands
Nucleoside vs Nucleotides
- Nucleoside:
a sugar with an
attached base
- Nucleotide:
a nucleoside with a
phosphate group
attached at carbon
atom 5’ or 3’
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Knowing DNA
Identifying Transformation Principle
Does DNA carry The Genetic information?
G
Griffith’s
t s eexperiments
pe
e ts
showed that some
genetic material
from the dead bacteria
was being transferred
to the living
bacteria and providing
them with a new trait.
However,
oweve ,
Griffith did not know
what the
transformation
substance was.
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Identifying Transformation Principle
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Experiment on T2 bacteriophage
These results indicated that contaminating RNA and proteins
in the extract was not acting as the genetic material.
However, when the extract was treated with DNase, its ability
to convert type IIR into type IIIS was lost. These results
indicated that the degradation of the DNA in the extract by
DNase
prevented conversion of type IIR to type IIIS.
This interpretation is consistent with the hypothesis that DNA is
the
genetic material. In other word the transformation principle is
DNA.
Life cycle of T2 bacteriophage
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Experiment on T2 bacteriophage
By Hershey and Chase (1952)
Interpretation:
1. Most of the phase DNA was found in the bacteria.
2. Most of the phase proteins was found in the supernatant.
So:
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DNA is the genetic material.
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Discovery of DNA Structure
Discovery of DNA Structure
Background data available to Watson and Crick:
1. Discovery of double helical structure of protein
by Linus Pauling
2. X-ray diffraction data about DNA structure
by Rosalind Franklin
3. Analysis of base composition of DNA by Erwin Shargaff (A/T,
G/C rule))
James Watson
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Francis Crick
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Double Helical Structure of DNA
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Double Helical Structure of DNA
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Complementary nature of double helix
Complementary nature of double helix is
basis for DNA hybridization
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Unusual Structures of DNA
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Thank You For Your Attention!!!
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