Classical Genetics
The Genome Contains
The Entirety Of An
Organism's Hereditary
Information.
If the DNA from a single (diploid) human cell were
connected end-to-end and straightened, it would
have a length of ~2 m and a width of ~2.4
nanometers
Challenge
In humans the entire stretch of DNA
polymer is made of ~ 3·109 monomer units
Question:
IF YOU HAD A REALLY LONG STRING HOW
WOULD YOU ORGANIZE IT?
Another Question
WHAT IF FROM TIME TO TIME YOU HAD TO
ACCESS PART OF THE STRING?
highly condensed nuclear structures
histone proteins
The DNA is compacted
into Chromosomes.
highly condensed nuclear structures
histone proteins
The DNA is compacted
into Chromosomes.
Humans Have 23 Pairs
of Chromosomes in
(Diploid) Cells
Humans Have 23 Pairs
of Chromosomes in
(Diploid) Cells
Gene is a stretch of DNA that contains the
instructions for making a protein
With Better
Understanding of
Genomics, The
Definition Of A Gene
Has Changed
DNA segment that encodes
for a protein
when and where it is made
new definition of a Gene
6 Atomic Constituents:
C, H, N, O, P, S Build
99.6% Of All Living
Matter
This small subset of atoms provides an extensive molecular diversity
All life is based on complex
structures (DNA, RNA, Proteins)
areformade
3 essentialwhich
biomolecules
existenceof these 6
and continuationelements
of life:
DNA, RNA: 4 nucleic bases
Proteins: 20 amino acids
variable units
Genetic code for DNA
2 strands of backbone
locked by base pairs
double helix
4 Nucleic Bases:
Adenine (A), Thymine (T), Guanine (G), and Cytosine (C)
Adenine
Guanine
Thymine
Cytosine
Genetic code for DNA
2 strands of backbone
locked by base pairs
double helix
4 Nucleic Bases:
Adenine (A), Thymine (T), Guanine (G), and Cytosine (C)
Thymine
Adenine
Pairing
A-T
G-C
Guanine
Cytosine
H-bonding  attractive force
between one electronegative atom
(O,F, N) and a hydrogen covalently
bonded to another electronegative
atom.
Hydrogen Bonding
Helps Stabilize DNA
Hydrogen Bonding
Helps Stabilize DNA
example:
Kevlar derives part of its high strength from
inter-molecular hydrogen bonds on
neighboring polymer chains and aromatic
(ring) stacking interactions between stacked
strands
Nucleotide Pairing Is
A Result of Hydrogen
Bonding
0.34 nm
Repetitive Structure
Backbone
Uniform Helix
The Structure of DNA
chemical variability
nucleic bases in arbitrary sequence
The Structure of DNA
Notice that the widths of the pairs A-T
and G-C are equal
base -sequence encodes the meaning
Base compositions experimentally determined for a
variety of organisms
Species
A:T
G:C
A:G
H. sapiens
1.00
1.00
1.56
Salmon
1.02
1.02
1.43
Wheat
1.00
0.97
1.22
Yeast
1.03
1.02
1.67
E. coli
1.09
0.99
1.05
S.
0.95
0.86
0.70
marcescens
The Structure of DNA
and Franklin
Watson, Crick…
Watson and Crick
The structure of DNA:
Notice that the widths of the
pairs A-T and G-C are equal
The structure of DNA:
chemical variability
nucleic bases in arbitrary sequence
repetitive structure
• backbone
• uniform helix
Notice that the widths of the
pairs A-T and G-C are equal
base -sequence encodes the meaning
Physically Repetitive, Chemically Variable
Why is this significant ?
The structure of DNA:
chemical variability
nucleic bases in arbitrary sequence
repetitive structure
• backbone
• uniform helix
Notice that the widths of the
pairs A-T and G-C are equal
base -sequence encodes the meaning
Physically Repetitive, Chemically Variable
 Readability requires some
sort of regular structure that can be
algorithmically sifted through
(semi-conservative replication)
 Chemically variability in sequence
provides a meaning and
a genetic diversity
DNA Replication Is
Semi-Conservative
Provides opportunity for introduction and preservation of Novelty
semi-conservative replication of DNA
Genetic code for RNA
1 strands of backbone
with base pairs
single helix
4 Nucleic Bases:
Adenine (A), Uracil (U), Guanine (G), and Cytosine (C)
Adenine
Guanine
Triplet of RNA bases (codon) translates into a particular amino acids
Uracil
Cytosine
The Genetic Code
Consists of Triplets of
Bases Called Codons
The Order of Amino
Acids Helps
Determine the Shape
of the Protein
Overview of What We’ve Discussed This AM:
The structure of DNA:
Shape governs the Function (Meaning)
The Hershey-Chase
Use a Virus
Experiments: What
the
Let it infectis
a bacteria
Radioactively label DNA & Proteins:
Hereditary Material Proteins or
DNA?
32P-labeled
DNA
35S-labeled
Protein
The Hershey-Chase
Experiments: DNA is the
Hereditary Material
2/3 within bacterium
32P-labeled
DNA
35S-labeled
Protein
1/4 within bacterium
The Central Dogma of
Molecular Biology:
1) DNA encodes RNA
2) RNA encodes Proteins
3) Proteins encode shape/function
DNA  RNA  Protein
 Genetic information (the MEANING) is encoded in the
SEQUENCE of basis along the DNA strand;
 DNA is not a direct template for protein synthesis;
The History of Classical Genetics
NATURE|Vol 441|25 May 2006
Classical Genetics
NEW CORE CURRICULUM: FOUNDATIONS OF THE SCIENTIFIC PROCESS
The Central Dogma of
Molecular Biology:
1) DNA encodes RNA
2) RNA encodes Proteins
3) Proteins encode shape/function
DNA  RNA  Protein
Genetic information (the MEANING) is encoded in the SEQUENCE
of basis along the DNA strand;
DNA is not a direct template for protein synthesis;
In the beginning…
Mendel
NATURE|Vol 441|25 May 2006
Johansen
Morgan
1941. Single Genes… Single
Enzymes
Johansen
Beadle
Tatum
1944. Genes are Made of DNA
Avery
MacLeod
McCarty
1953. Structure of DNA
Watson
Crick
Wilkins
Franklin
1977. Introns
Roberts
Sharp
1993. The first μRNA identified
in C. elegans
Establishing Basic Terminology and Definitions:
Gene = is a stretch of DNA that contains the instructions for making a protein;
Allele = alternative forms of genes for a certain characteristics
alleles for flower color or earlobe shape);
Homozygous (EE, ee) & Heteorzygous (Ee);
(ex.
Genotype = genetic makeup of an organism;
Phenotype = observed characteristics of organism;
The phenotype is produced by the interaction of genes and the environment.
It has been long known that offspring
resemble parents.
Animals and plants selectively bred for
many centuries.
Gregor Mendel was the first to explain
the principles of heredity in the midnineteenth century. He investigated
heredity in pea plants
Pea Plants have distinctive characters:
Purple OR White flowers
Garden pea grow easily, produce
large numbers of seeds quickly, and
self-fertilize.
Scientific Process of discovery….establishing Classical Genetics
Mendel isolated true-breeding strains
Traits were selected because they had two distinct phenotypes
Mendel crossbred plants with different
alleles
Gamete is a cell that is involved in
sexual reproduction.
A male and female gamete unite to produce a
zygote that will develop into offspring.
Interpretation of Mendel’s Results  Laws of Heredity:
Law of dominance: When an organism has 2 alleles for a given trait, the
allele that is expressed (overshadows the expression of the other allele) is
the dominant allele. The overshadowed allele is called recessive allele.
notation convention:
Y - dominant allele (ex. purple)
y - recessive allele (ex. white)
• YY - homozygous dominant
• Yy - heterozygous
• yy - homozygous recessive
Recessive traits are usually the result of a mutation causing loss or
modification of gene product.
ex.
Albinism: characterized by the complete or partial absence of pigment in the skin,
hair and eyes due to absence or defect of an enzyme involved in the production of melanin
Deleterious recessive alleles
persist in the population
because heterozygous individuals
carry the allele without developing
the phenotype, and are not
at a selective disadvantage.
If both parents are homozygous
for the recessive trait, all their progeny will
usually also have the trait.
You could construct a family tree of either your family or friend’s family by using character
for ear lobe type (recessive vs. dominant)
non-attached is dominant
Co-Dominance
Both alleles, when present, will contribute
equally to the phenotype.
Blood typing in humans- the ABO
system; Rh factor incompatibility
(erythrobalstosis feotalis).
Terms: antigen, antibody, agglutination,
Rh factor
Co-Dominance
Co-Dominance
Incomplete
Dominance
Interpretation of Mendel’s Results  Laws of Heredity:
Law of dominance: When an organism has 2 alleles for a given trait, the
allele that is expressed (overshadows the expression of the other allele) is
the dominant allele. The overshadowed allele is called recessive allele.
Law of segregation: Parental alleles of a gene separate in process called
meiosis into gametes (reproductive cells). In the process of gametes
formation, the alleles that control a trait separate form one another retaining
their individuality.
Law of independent assortment: If two different genes are found on
separate chromosomes, where the one allele goes is not influenced by
where the other goes.
Law of Segregation
Law of Independent
Assortment
parental alleles of a gene separate in process
semi-conservative replication of DNA
called meiosis into gametes
Next time…more about current
efforts in Genetics