Download From DNA to Phenotype

Wheeler High School
The Center for Advanced Studies in Science, Math & Technology
Course Introduction
Genetics Lecture 1
Post-AP DNA/Genetics – Mrs. Kelavkar
What Is A Gene?
• We shall begin with the physical definition of
a gene. Conceptually, this is quite simple
and gives us a chance to refresh our minds.
Post-AP DNA/Genetics – Mrs. Kelavkar
• Genes are made of DNA
Watson & Crick
• 1953
• Deduced structure of DNA as double helix
– With a little help from Rosalind Franklin
• Complementary base pairing (Chargaff)
– Showed how information could be encoded in a
molecule & duplicated
• Thus REPLICATION
Post-AP DNA/Genetics – Mrs. Kelavkar
Gene Expression:
From DNA to Phenotype
• TRANSCRIPTION
– Uses complementary base pairing
– Makes mRNA
• RNA is chemically less stable than DNA
• Think of mRNA as a temporary molecule that stores
DNA’s information
Post-AP DNA/Genetics – Mrs. Kelavkar
Initiation of Transcription
Transcription begins at the 5’ end of the gene in a
region called the promoter.
The promoter recruits TATA protein, a DNA binding
protein, which in turn recruits other proteins.
TATA binding protein
Promoter
DNA
GG
Transcription factor
Gene sequence
to be transcribed
TATA
TATA box
Transcription begins
When a complete transcription complex is formed RNA
polymerase binds and transcription begins.
Translation
The process of reading the RNA sequence of an mRNA and
creating the amino acid sequence of a protein is called
translation.
DNA
Transcription
T
T
C
A
G
T
C
A
G
A
A
G
U
C
A
G
U
C
DNA
template
strand
Messenger
RNA
mRNA
Codon
Codon
Codon
Translation
Protein
Lysine
Serine
Valine
Polypeptide
(amino acid
sequence)
Make me a protein!
(Remember…”Structure equals function”)
You see…
it’s all about
the proteins.
Cellular processes depends on
protein structure AND the amino acid
combinations that make them!
Having Said That…
What is a GENE?
A DNA segment that is needed to make a
protein.
Post-AP DNA/Genetics – Mrs. Kelavkar
Genes
• Usually 103 – 104 bp in size
– Human dystrophin gene is 2 x 106 bp
• Connects muscle fibers to cell membrane
• E. coli has ~4,200 genes
– Not very many
– There are more than 1,000 different enzymes
needed to carry out the necessary biological
reactions in an E. coli cell
Post-AP DNA/Genetics – Mrs. Kelavkar
Dystrophin
Connects the
muscle fibers to
the cell’s
membrane
through the extracellular matrix.
‘Irregular’ dystrophin =
muscular dystrophy
Post-AP DNA/Genetics – Mrs. Kelavkar
More Complex Organisms
• Humans have ~35,000 genes
– Genes are located on chromosomes
There is a fairly predictable flow to it all…
Gene → Protein → Cell Processes → Organism
It may be simple, but it illustrates 2 very powerful
aspects of genetic analysis.
Post-AP DNA/Genetics – Mrs. Kelavkar
The 2 Important Aspects
1. We can study microscopic changes in DNA
and these changes are revealed by
phenotype
2. We can study the function of individual
proteins by examining the consequences of
eliminating that one protein function
(‘knockout’ mice)
These are 2 of the main themes studied in
genetics!
Some Terms You Should Know
Alleles: Different versions of the same gene
Mutation: An altered version of a gene
Genotype: All of the alleles in an organism
Phenotype: The physical result of the genotype
Wild Type: It’s the standard (think of it like the
control)
Post-AP DNA/Genetic – Mrs. Kelavkar
Any Questions?
Post-AP DNA/Genetics – Mrs. Kelavkar
Wheeler High School
The Center for Advanced Studies in Science, Math & Technology
Model Organisms & Key Players
Genetics Lecture 2
Post-AP DNA/Genetics – Mrs. Kelavkar
Table 1-2
Copyright © 2006 Pearson Prentice Hall, Inc.
Model Organisms
Why do genetic studies rely on the use of
model organisms?
1.
2.
3.
4.
Short life cycle
Easy to maintain in the lab (usually)
Lots of offspring
Fairly straightforward genomes & anatomy
Post-AP DNA/Genetics – Mrs. Kelavkar
Escherichia coli
E. coli
• Gram negative
• Different serotypes
– Different serotypes = different surface antigens
• Named after Austrian doctor, Theodor von
Escherich, who isolated it from the intestines of
animals
–
–
–
–
Isolated in 1922
First bacterium to have genome sequenced
~4.6 million bases
Important because it has many genes that are found in
common organisms
Post-AP DNA/Genetics – Mrs. Kelavkar
Escherichia coli
E. coli
•Studied by many early
geneticists
–Most famous is Avery,
MacLeod & McCarty’s
1944 experiment
illustrating transformation
• Remember that
“transformation” was
first described by Griffith
in 1928
–Experiment showed
DNA was genetic material
Post-AP DNA/Genetics – Mrs. Kelavkar
T Phage infecting E. coli
Viruses that infect bacteria are called
bacteriophages (geeky geneticists call
them ‘phages’ for short).
Seymour Benzer genetically
mapped >2400 mutations in
the T4 rII gene.
Figure 1-7
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Saccharomyces cerevisiae
Yeast
Why do geneticists love yeast?
1. Non pathogenic eukaryote
2. Grows rapidly on glucose
3. Easy transformation
4. ~6,000 genes, all sequenced
Drosophila melanogaster
Fruit fly
•Used to study humanspecific diseases
•3 pairs of autosomes and
an X and Y
•Life cycle & mating
behavior very well
understood
–Morgan & Benzer
–Many mutants identified
–Almost ALL genes have
human orthologs
Figure 1-6
Copyright © 2006 Pearson Prentice Hall, Inc.
Drosophila melanogaster
Fruit fly
Thomas Hunt Morgan & his “Raiders”
• Discovered the following (and many more):
–
–
–
–
White-eye mutation
Sex-linkage & segregation
Nondisjunction & crossing-over
The “clock” gene
• Benzer worked on this too. He was convinced that
our circadian rhythms had a genetic basis.
– “Notch” gene
• Led to discovery of Huntington’s mutation
Post-AP DNA/Genetics – Mrs. Kelavkar
Caenorhabditis elegans
C. elegans
•
•
•
•
•
Soil dwelling nematode
~1 mm
Sydney Brenner (1974)
Has nervous system
First multicellular organism to have it’s
genome sequenced
• Many conserved protein sequences &
human orthologs
– Shows quick evolutionary patterns
Post-AP DNA/Genetics – Mrs. Kelavkar
Danio rerio
Zebrafish
Mutation in
the pigment
gene (1 bp
difference
in humans).
• Vertebrate, Freshwater
• Used to study embryonic development and
development of vertebrates
– Large, transparent eggs
• Mutations in the two cell singaling genes,
PSEN1 and PSEN2, are studied in zebrafish
– Mutations in these genes can lead to
Alzheimers disease
Post-AP DNA/Genetics – Mrs. Kelavkar
Mus musculus
The common mouse
• Mammals and therefore share a high degree
of homology with humans
• ~3 billion bp’s
• Knockout mice – gene is ‘knocked out’;
used to study function of genes
• Oncomice – activated oncogene mutant;
lead to cancer
• Transgenic mice – foreign genes inserted
in to their genome
Post-AP DNA/Genetics – Mrs. Kelavkar
What causes obesity? Genetics,
environment, combo of both?
Post-AP DNA/Genetics – Mrs. Kelavkar
Some Terms You Should Know
• Homologue: A gene related to a second gene by
descent from a common ancestral DNA sequence.
There are 2 main types of homologues…
– Ortholog: genes in different species that evolved from a
common ancestral gene by speciation (normally,
orthologs retain the same function in the course of
evolution)
• Always the result of speciation
– Paralogs: genes related by duplication within a genome
• Orthologs retain the same function in the course of evolution,
whereas paralogs evolve new functions
Post-AP DNA/Genetics – Mrs. Kelavkar
Any Questions?
Yes…we will study C. elegans and you will need to
understand their mating patterns.
Post-AP DNA/Genetics – Mrs. Kelavkar
1.1 From Mendel to DNA
in Less Than a Century
1.1.2 The Chromosome Theory of
Inheritance: Uniting Mendel and Meiosis
Figure 1-2
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Figure 1-3
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Figure 1-5
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1.1 From Mendel to DNA
in Less Than a Century
1.1.3 Genetic Variation
Mendel 1857
1.1 From Mendel to DNA
in Less Than a Century
1.1.4 The Search for the Chemical Nature of
Genes: DNA or Protein?
Fredrick Griffith 1928
Non-virulent bacteria transformed to virulent strain
Thomas Morgan 1933
Chromosome as heredity material
1.2 Discovery of the Double
Helix Launched the
Recombinant DNA Era
1.2.1 The Structure of DNA and RNA
Rosalind Franklin 1953-56
Maurice Wilkins and Watson & Crick 1953-58
Figure 1-8
Copyright © 2006 Pearson Prentice Hall, Inc.
1.2 Discovery of the Double
Helix Launched the
Recombinant DNA Era
1.2.2 Gene Expression:
From DNA to Phenotype
Edwin Chargaff 1940’s
AT & GC Complimentary rule
Figure 1-9
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1.2 Discovery of the Double
Helix Launched the
Recombinant DNA Era
1.2.3 Proteins and Biological Function
Messelson and Stahl
Semiconservative mode of replication 1958-59
Figure 1-10
Copyright © 2006 Pearson Prentice Hall, Inc.
1.2 Discovery of the Double
Helix Launched the
Recombinant DNA Era
1.2.4 Linking Genotype to Phenotype:
Sickle-Cell Anemia
Figure 1-11
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Figure 1-12
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Figure 1-13
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1.3 Genomics Grew Out of
Recombinant DNA
Technology
1.3.1 Making Recombinant DNA Molecules
and Cloning DN
Figure 1-14
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1.3 Genomics Grew Out of
Recombinant DNA
Technology
1.3.2 Sequencing Genomes:
The Human Genome Project
1992-93 Beginning
2002-2003 Completed
Craig Venter
Celera Genomics & J. Craig Venter Institute
Francis Collins Physician - geneticist
Director of National Institutes of Health
Figure 1-15
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1.4 The Impact of Biotechnology
Is Growing
1.4.1 Plants, Animals, and the Food Supply
Table 1-1
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Figure 1-16
Copyright © 2006 Pearson Prentice Hall, Inc.
1.4 The Impact of Biotechnology
Is Growing
1.4.2 Who Owns Transgenic Organisms?
Figure 1-18
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1.5 Genetic Studies Rely On the
Use of Model Organisms
Why? What are the advantages to
researchers?
1.5 Genetic Studies Rely On the
Use of Model Organisms
1.5.1 The Modern Set of Genetic Model
Organisms
1.5 Genetic Studies Rely On the
Use of Model Organisms
1.5.2 Model Organisms and Human Diseases
Zoonotic Diseases
Animals to Humans transmission & visa versa