Transcript Chapter 25: Molecular Basis of Inheritance

Chapter 25: Molecular Basis
of Inheritance
DNA was shown to be the genetic material
(rather than proteins) by a simple
experiment.
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Viral DNA is labeled
Fig 25.1
Different parts of the phage were
radioactively labeled (shown in red).
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Viral capsid is labeled
Fig 25.1
The experiments showed that only the virus
DNA entered the bacteria and produced
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new viruses.
One pair of bases
DNA is a polynucleotide
composed of a
phosphate, a sugar, and
four nitrogen-containing
bases: adenine (A),
thymine (T), guanine
(G), and cytosine (C).
Fig 25.2
Pyrimidine
Purine
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The structure of DNA was determined by
James Watson and Francis Crick in the
early 1950’s and they showed that DNA is
a double helix in which A is paired with T
and G is paired with C.
This is called complementary base pairing
because a purine (2 rings) is always
paired with a pyrimidine (1 ring).
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DNA double helix
When the DNA double
helix untwists, it
resembles a ladder:
Fig 25.2
Hydrogen
Bond
Sides =
sugar+phosphate
Rungs = complementary
paired bases.
The two DNA strands
are anti-parallel – they
run in opposite
directions
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Replication of DNA
DNA replication occurs during
chromosome duplication; an exact copy
of the DNA is produced with the aid of
DNA polymerase.
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Overview of DNA replication
Fig 25.3
Hydrogen bonds
between bases break
and enzymes “unzip”
the molecule.
Each old strand of
nucleotides serves as
a template for each
new strand.
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Ladder configuration and DNA
replication
New nucleotides move
into complementary
positions and are joined
by DNA polymerase.
Fig 25.4
Old Strands
The process is
semiconservative. Each
new double helix is
composed of an old
strand and a newlyformed strand.
New Strands
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Gene Expression
A gene is a segment of DNA that specifies
the amino acid sequence of a protein.
Gene expression occurs when gene
activity leads to a protein product in the
cell.
A gene does not directly control protein
synthesis; DNA is transcribed into RNA,
RNA is translated in amino acids which
are used to make proteins.
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RNA (ribonucleic acid)
Three types of RNA:
messenger RNA (mRNA) carries genetic
information to the ribosomes, RNA
copy of DNA
ribosomal RNA (rRNA) is found in the
ribosomes, and
transfer RNA (tRNA) transfers amino
acids to the ribosomes, where the
protein product is synthesized.
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Structure of RNA
RNA is a singlestranded nucleic
acid in which A
pairs with U
(uracil) while G
pairs with C.
Fig 25.5
DNA=T-A;G-C
RNA=U-A;G-C
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Two processes are involved in the synthesis of
proteins in the cell:
Transcription makes an RNA molecule
complementary to a portion of DNA (a
section of DNA instruction is copied).
Translation occurs when the sequence of
bases of mRNA directs the sequence of
amino acids in a polypeptide (instructions
are followed to build a protein).
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The Genetic Code
DNA specifies the synthesis of proteins
because it contains a triplet code: every
three bases stand for one amino acid.
Each three-letter unit of an mRNA
molecule is called a codon.
The code is nearly universal among living
organisms.
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Codons
TTAGCCACGATC
AATCGGTGCTAG
Double Stranded
DNA
AATCGGTGCTAG
Each group of three bases = one codon
Each codon is the ‘code’ for a specific
amino acid.
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Messenger RNA codons
Fig 25.6
123 = amino acid
AUA = isoleucine
CCG = proline
GAU = aspartate
GAC = aspartate
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Central Concept
The central concept of genetics involves
the DNA-to-protein sequence involving
transcription and translation.
DNA has a sequence of bases that is
transcribed (copied) into a sequence of
bases in mRNA.
Every three bases is a codon that stands
for a particular amino acid.
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Overview of gene expression
Fig 25.7
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Transcription and mRNA synthesis
Fig 25.8
During transcription in the
nucleus, a segment of DNA
unwinds and unzips, and the
DNA serves as a template for
mRNA formation.
RNA polymerase joins the
RNA nucleotides so that the
codons in mRNA are
complementary to the triplet
code in DNA.
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Translation
Translation is the second step by which
gene expression leads to protein
synthesis.
During translation, the sequence of
codons in mRNA specifies the order of
amino acids in a protein.
Translation requires several enzymes
and two other types of RNA: transfer
RNA and ribosomal RNA.
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Transfer RNA
During translation, transfer RNA (tRNA)
molecules attach to their own particular
amino acid and travel to a ribosome.
Through complementary base pairing
between anticodons of tRNA and
codons of mRNA, the sequence of
tRNAs and their amino acids form the
sequence of the polypeptide.
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Fig 25.10
Transfer RNA: amino acid carrier
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Anticodon
Anticodon for
the first codon
Part of tRNA
UUA
AAUCGGUGCUAG
mRNA
Codons
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Ribosomal RNA
Ribosomal RNA, also called structural
RNA, is made in the nucleolus.
Proteins made in the cytoplasm move
into the nucleus and join with
ribosomal RNA to form the subunits of
ribosomes.
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Translation Requires Three
Steps
During translation, the codons of an
mRNA base-pair with tRNA
anticodons.
Protein translation requires these steps:
1) Chain initiation
2) Chain elongation
3) Chain termination.
Enzymes are required for each step, and
the first two steps require energy.
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Chain Initiation
Fig 25.12
First, a small
ribosomal subunit
attaches to the mRNA
near the start codon.
The anticodon of
tRNA, called the
initiator RNA, pairs
with this codon.
Then the large
ribosomal subunit
joins.
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Chain Elongation
Fig 25.12
The ribosome
moves forward
and the tRNA at
the second
binding site is
now at the first
site, a sequence
called
translocation.
The previous
tRNA leaves the
ribosome and
picks up another
amino acid before
returning.
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Chain Termination
Fig 25.12
Chain termination occurs
when a stop-codon
sequence is reached.
The polypeptide is
enzymatically cleaved
from the last tRNA by a
release factor.
A newly synthesized
polypeptide may function
alone or become part of a
protein.
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Polyribosome structure and function
Fig 25.11
Several ribosomes may attach and
translate the same mRNA, therefore
the name polyribosome.
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Review of Gene Expression
DNA in the nucleus contains a triplet
code (codons); each group of three
bases stands for one amino acid.
During transcription, an mRNA copy of
the DNA template is made.
The mRNA joins with a ribosome, where
tRNA carries the amino acids into
position during translation.
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Gene expression
Fig 25.13
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Gene Mutations
A gene mutation is a change in the
sequence of bases within a gene.
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Frameshift Mutations
Frameshift mutations involve the addition
or removal of a base during the formation
of mRNA; these change the genetic
message by shifting the “reading frame.”
Codon sequence:
THE CAT ATE THE RAT
If C in cat is removed:
THE ATA TET HER AT
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Point Mutations
Point mutation (3 types) - The change of just
one nucleotide causing a codon change
-can cause the wrong amino acid to be
inserted in a polypeptide.
1) Silent mutation, change in the codon
results in the same amino acid.
CUC and CUA both code for Leucine
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2) Nonsense mutation - If a codon is
changed to a stop codon, the resulting
protein may be too short
3) Missense mutation - the substitution
of a different amino acid, the protein
cannot reach its final shape
An example is Hbs which causes sicklecell disease.
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Fig 25.17
Sickle-cell disease in humans
Chain is 146 AA’s long
One change in the sixth position
GUA & GUG = Valine
GAA & GAG = glutamate
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Cause and Repair of Mutations
Mutations can be spontaneous or caused
by environmental influences called
mutagens.
Mutagens include radiation (X-rays, UV
radiation), and organic chemicals (in
cigarette smoke and pesticides).
DNA polymerase proofreads the new
strand reducing mistakes to one in a
billion nucleotide pairs replicated.
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Cancer: A Failure of Genetic
Control
Cancer is a genetic disorder resulting in
a tumor, an abnormal mass of cells.
‘Unregulated Cell Growth’
Carcinogenesis - the development of
cancer.
Cancer cells fail to undergo apoptosis, or
programmed cell death.
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Cancer cells
Cancer cells lack
differentiation,
form tumors,
undergo
angiogenesis
and metastasize.
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Angiogenesis (stimulated by cancer
cells) is the formation of new blood
vessels.
Metastasis is invasion of other tissues by
establishment of tumors at new sites.
A patient’s prognosis is dependent on
the degree to which the cancer has
progressed.
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Origin of Cancer
1) Mutations in genes for DNA repair
enzymes can contribute to cancer.
2) Mutations in genes that code for
proteins regulating structure of
chromatin can promote cancer.
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3) Mutations in Proto-oncogenes or
tumor-suppressor genes can prevent
normal regulation of the cell cycle.
4) Telomeres are DNA segments at the
ends of chromosomes that normally
get shorter and signal an end to cell
division; cancer cells have an enzyme
that keeps telomeres long.
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Oncogenes
Proto-oncogenes – involved with
stimulating cell division
Proto-oncogenes can undergo mutations
to become cancer-causing oncogenes.
Oncogenes are responsible for
uncontrolled cell growth.
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Tumor-Suppressor Genes
Tumor-suppressor genes – involved with
suppressing cell division.
When Tumor-suppressor genes mutate,
they stop suppressing the cell cycle
and it can occur nonstop.
The balance between stimulatory signals
and inhibitory signals determines
whether proto-oncogenes or tumorsuppressor genes are active.
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Causes of cancer
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Stop
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Chapter 23:
Know why Gregor Mendel is important
What does homologous, allele, loci, gene, chromosome,
genotype, and phenotype mean?
What is the relationship between dominant and recessive
alleles. How does inheritance work? How many copies of each
allele are found in gametes?
What is a one-trait cross? What are the possible outcomes
(genotype & phenotype) based on the parents
genotypes/phenotypes. Same questions for two-trait cross.
What is a pedigree chart and what is it used for. Understand
how to do a pedigree analysis.
What is an autosome? What is autosomal dominant versus
autosomal recessive? Also polygenic traits, incomplete
dominance,and codominance.\
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Review blood type and sickle cell disease.
Chapter 24:
Know what karyotyping is and what it can be used for.
Understand how changes in chromosome number, what can
happen, and why that is important.
Understand how changes in sex-chromosomes affect a
persons phenotype/genotype and associated syndromes.
How can changes in chromosome structure occur?
What is a sex-linked trait and how are they inherited?**
Understand how autosomal and sex-linked inheritance of traits
works.
Do the practice problems!!
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Chapter 25:
How was it discovered that DNA was the source of genetic
information
What is the structure of DNA? How is it replicated?
What is RNA? How is it different than DNA? What types of
RNA are there and why?
What is a codon? What are they used for?
What is gene expression? What are the processes that lead to
gene expression.
Understand Translation and Transcription and all steps
involved.
What are some types of gene mutations and how do they work.
Understand the mechanisms of cancer growth.
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