Download Lecture 6: DNA and molecular genetics

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The lowdown on DNA and the genetic code
• information for living organisms is encoded in a four letter code in the sequence of a
very long molecule called deoxyribonucleic acid (DNA)
• DNA consists of two strands twisted around each other to form a double helix
• Most of our DNA is stored in the nucleus of cells although some DNA exists inside the
mitochondria
• The genetic code is formed by four different bases: cytosine (C), thymine (T), adenine
(A), and guanine (G). One of the strands is the coding (sense) strand, while the
other is the non-coding (antisense
).
(antisense).
• Bases pair up by weak bonds allowing for easy copying and replication of the DNA
strands: the strands unzip and build two more by addiing bases to each strand.
The template also acts as quality control to check for correct pairing and error
correction if necessary
• DNA is transcribed into messenger RNA that is translated into protein. The sequence
encoding a single protein is called a gene.
• Humans have about 3 billion base pairs of DNA containing perhaps 60,000 genes. For
those keeping score, this means that most of our DNA doesn’
doesn’t code for anything
(junk DNA)
Is this clear? Dr. Sussman makes it easy!
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Outline
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DNA Structure and Function
DNA Replication
RNA Structure and Function
– Types of RNA
Gene Expression
– Transcription
– Translation
Biotechnology
Human Genome
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DNA and RNA Structure and Function
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DNA is the genetic material found
principally in chromosomes.
– In between cell divisions, chromosomes
exist in long fine threads of chromatin.
v When a cell is about to divide,
chromosomes coil and condense.
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DNA Location and Structure
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DNA Structure and Replication
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DNA is a sequential series of joined
nucleotides.
– Sugar (deoxyribose), phosphate, and base.
v Adenine (A).
v Thymine (T).
v Cytosine (C).
v Guanine (G).
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DNA Structure and Replication
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DNA is a double helix with a sugarphosphate backbone and bases projecting
between the backbones.
– Exhibits complementary base pairing.
v A-T.
v G-C.
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DNA Replication
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Replication Steps.
– Hydrogen bonds between strands break
and the molecule unzips.
– New nucleotides fit beside parental
strand.
– DNA polymerase joins new nucleotides.
– Two complete molecules present, each
with one old strand and one new strand.
v Semi-conservative replication.
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DNA Replication
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Structure and Function of RNA
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RNA is made up of nucleotides containing
the sugar ribose and the base uracil in
place of thymine.
– Single stranded.
v RNA is a helper to DNA allowing
protein synthesis.
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Types of RNA
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Ribosomal RNA.
– Joins with proteins made in the
cytoplasm to form the subunits of
ribosomes.
Messenger RNA.
– Carries genetic information from DNA to
the ribosomes in the cytoplasm where
protein synthesis occurs.
Transfer RNA.
– Transfers amino acids to the ribosomes
where amino acids are joined.
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RNA structure: like DNA, but different
mRNA - (messenger) template for protein
synthesis
tRNA - (transfer) brings amino acids to
ribosomes
rRNA - (ribosomal) forms ribosomal subunits
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DNA Code
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Genetic code is essentially universal.
– Contains a triplet code.
v Every three bases represents one
amino acid.
Transcription.
– Strand of mRNA forms that is
complementary to a portion of DNA.
v Triplet of mRNA is termed a codon.
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Found in translation: mRNA to protein
• The triplet code: each three bases codes for a single
amino acid
• Transcription
ranscription is the process of creating the mRNA strand
from DNA
• Translation is the process of converting the mRNA
sequence into protein
• Production of DNA and RNA strands is
performed by enzymes called polymerase
• Start and stop codons specify beginning and end of
protein coding sequences
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Transcription of DNA leads to
production of mRNA strand
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Processing of mRNA
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Most human genes are interrupted by
introns.
– Intragene segments interrupt gene
segments, exons.
v During processing, introns are
removed and exons are joined to form
an mRNA molecule.
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Exons and introns:
introns: creating alternative
products from a single mRNA
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Translation
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Translation is the synthesis of a polypeptide
under the direction of an mRNA molecule.
– Transfer RNA molecules bring amino
acids to the ribosomes.
v Anticodon is triplet complementary to
an mRNA codon.
Polypeptide synthesis requires three steps.
– Initiation.
– Elongation.
– Termination.
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tRNA anticodon - mRNA codon pairing
brings the amino acids in line
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Elongation of the peptide chain:
nascent protein synthesis
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Polyribosomes - making multiple protein
strands off of a single mRNA template
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Gene Expression Review
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DNA triplet codes for a specific amino acid.
During transcription, a segment of DNA
serves as a template for mRNA.
Messenger RNA has introns removed.
Messenger RNA carries a sequence of
codons to the ribosomes.
Transfer RNA molecules have anticodons
complementary to mRNA codons.
Linear sequence of mRNA codons
determines order amino acids are
incorporated into a protein.
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Putting it all together: from DNA to protein
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Point mutation: changing the protein product
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Effects of mutations: causing genetic disorders
• Point mutants: a single base change - remains in frame
• Frameshift mutants: add or lose a make changes downstream
triplet code
• examples:
• hemophilia B - premature stop codon
•Cystic fibrosis -altered chloride channel sequence
• androgen insensitivity - altered androgen receptor
renders individual nonresponsive to
testosterone (possesses testes but appears
as female)
faulty enzyme (Ea) can lead to impaired conversion of amino acid
leading to disease (phenylketonuria
). Alternatively, loss of enzyme
(phenylketonuria).
function (Eb
(Eb)) can lead to loss of protein production leading to
disease (albino).
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Regulation of Gene Expression
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Gene Regulation Mechanisms.
– Transcriptional control.
– Posttranscriptional control.
– Translational control.
– Posttranslational control.
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Biotechnology
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Genetic engineering is the use of
technology to alter the genomes of
organisms.
– Biotechnology includes genetic
engineering and other techniques to
make use of natural biological systems to
achieve an end desired by humans.
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Biotechnology Products
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Transgenic Bacteria.
– Insulin.
– Human Growth Hormone.
Transgenic Plants.
– Pest resistance.
v Higher yields.
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Biotechnology Products
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Transgenic Animals.
– The use of transgenic farm animals to
produce pharmaceuticals is currently
being pursued.
v Cloning transgenic animals.
ÿ Dolly (1997).
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The Cloning of a Gene
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Recombinant DNA Technology.
– Uses at least two different DNA sources.
v Vector used to introduce foreign DNA
into a host cell.
ÿ Plasmid.
Enzymes.
– Restriction enzymes cleave DNA.
– DNA ligase seals DNA into an opening
created by the restriction enzyme.
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Biotechnology:
genetic engineering to create
designer protein products
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Recombinant DNA: cutting and pasting
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Polymerase Chain Reaction
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Polymerase Chain Reaction (PCR) can
create millions of copies of a DNA segment
very quickly.
– Can be subjected to DNA fingerprinting
using restriction enzymes to cleave the
DNA sample, and gel electrophoresis to
separate DNA fragments.
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DNA fingerprinting by PCR
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Gene Therapy
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Gene therapy is the insertion of genetic material
into human cells to treat a disorder.
– Ex Vivo Gene Therapy.
v Bone marrow stem cells are removed from
the blood and infected with an RNA
retrovirus that carries a normal gene for the
enzyme.
ÿ Cells returned to patient.
– In Vivo Gene Therapy.
v Genes injected alone, or with a virus, directly
into the organ, or the body.
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Gene therapy: ex vivo manipulation of cells
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The Human Genome
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Genome is all the genetic information of an
individual or species.
– Base sequence map.
v Shows sequences of all base pairs.
ÿ Completed for humans.
– Genetic map.
v Shows locations of genes along each
chromosome.
ÿ Unfinished for humans.
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Mapping the location of genes on
chromosomes allows for identification of
loci associated with genetic diseases
Map of chromosome 17 from human reveals position
of multiple loci associated with diseases
Human genome project mapped human DNA
sequence with the promise of creating information
for novel approaches to pharmaceuticals,
idfentification of novel genes, discovering disease
loci, potential for better prenatal counseling
Ethical dliemma:
dliemma:
How much do we want to
know about our potential
defects or those of our
offspring?
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Review
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DNA Structure and Function
DNA Replication
RNA Structure and Function
– Types of RNA
Gene Expression
– Transcription
– Translation
Biotechnology
Human Genome
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