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Transcript
Altering the Genetic Message
Chapter 18
Copyright © McGraw-Hill Companies Permission required for reproduction or display
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Outline
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Mutations
Changes in Gene Position
Cancer
Recombination
Gene Transfer
Reciprocal Recombination
Trinucleotide Repeats
Eukaryotic DNA
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Mutations are Rare But Important
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•
Although organisms have evolved many
mechanisms to avoid errors during DNA
replication, mutations do occur.
 If changes were common, genetic
instructions would soon degrade.
All evolution begins with alterations in the
genetic message.
 Rate of evolution is ultimately limited by the
rate alternative combinations are produced.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Kinds of Mutation
•
Only mutations in the germ line (cells that
form gametes) are passed to subsequent
generations.
 Mutations in somatic cells may have large
effect on the individual, as they are passed
on to other cells in the same individual.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Kinds of Mutation
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•
Point Mutations
 Alterations involving one or a few base
pairs.
- Spontaneous pairing errors during
replication.
- Mutagens.
Transposition
 Individual genes may move within the
genome.
- Chromosomal Rearrangement
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Point Mutations
•
Physical Damage to DNA
 Ionizing Radiation
- Highly mutagenic. Produce free radicles
that cause a double-strand break.
 Can not be fixed by cell’s usual
mutational repair enzymes.
 Ultraviolet Radiation
- Strongly absorbed in pyrimidine bases.
 May form pyrimidine dimer.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Pyrimidine Dimer
Copyright © McGraw-Hill Companies
Permission required for reproduction or display
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Point Mutations
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Chemical Modification of DNA
 Three Chemical Classes
- Chemicals that repair DNA, but pair
incorrectly.
- Chemicals that remove the amino group
from adenine or cytosine.
- Chemicals that add hydrocarbon groups
to nucleotide bases.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Point Mutations
•
Chemical Modification of DNA
 Spontaneous Mutations
- Slipped mispairings are caused when
sequences misalign causing a portion of
one strand to loop out.
 Transitory - quickly repaired.
 If not reverted before the cell
corrects it, the segments will be
excised out, causing a deletion.
 Frame-Shift Mutation
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Changes in Gene Position
•
Chromosomal Rearrangement
 Translocations - Segments of one
chromosome become part of another
chromosome.
 Inversions - Orientation of a portion of
chromosome is reversed.
 Aneuploidy - Genes or chromosome
segments are added or deleted.
 Polyploidy - Entire sets of chromosomes
added.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Inversion
Copyright © McGraw-Hill Companies Permission required for reproduction or display
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Changes in Gene Position
•
Insertional Inactivation
 Transposons are capable of moving to
different locations in the genome.
- Select new locations at random.
 May cause insertional inactivation.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Cancer
•
Cancer is a growth disorder of cells.
 Uncontrolled and invasive growth.
- Results in tumor.
 May metastasize.
 Can be caused by mutagenic chemicals or
possibly viruses.
- Cell division never stops in a cancerous
line, and are thus essentially immortal.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Kinds of Cancer
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•
Sarcomas - Arise in connective tissue or
muscle.
Carcinomas - Arise in epithelial tissue.
 Carcinogens are agents thought to cause
cancer.
- Ames Test
 Carcinogenic chemicals are all mutagenic.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Tumors From Viral Infection
•
Rous avian sarcoma virus (RSV) has been
associated with chicken sarcomas.
 Retrovirus
- Cancer results from inappropriate
activity of growth-promoting genes that
are less active or completely inactive in
normal cells.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Cancer and the Cell Cycle
•
•
Transfection - Nuclear DNA from tumor cells is
isolated and cleaved into random fragments,
and tested for ability to induce cancer.
Single nucleotide substitutions (Point
mutations) have been shown to lead to cancer.
 Cells inhibition of telomerase in somatic
cells is a natural brake on cancer.
- Inactivation of inhibition may help induce
cancer.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Cancer and the Cell Cycle
•
Proto-oncogenes are genes encoding proteins
that stimulate cell division.
 Mutated proto-oncogenes become cancercausing genes (oncogenes).
- Mutated alleles of many oncogenes are
genetically dominant.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Cancer and the Cell Cycle
•
In healthy cells, cell division is normally turned
off by proteins encoding for tumor suppressor
genes.
 Almost half of all cancers involve mutations
of the p53 gene.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Cancer and the Cell Cycle
•
Cells control proliferation at several
checkpoints.
 All these controls must be inactivated for
cancer to be initiated.
- Induction of most cancers involves
mutations of several genes.
 Explains why most cancers occur in
people over 40.
 More time for individual cells to
accumulate multiple mutations.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Smoking and Cancer
•
About one-third of all cancer cases in the
United States are directly attributable to
cigarette smoking.
 Smoke contains many mutagenic
chemicals, and places them in direct
contact with lung tissues.
- Damages genes of epithelial cells lining
the lungs.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Curing Cancer
•
Preventing Start of Cancer
 Receiving Signal to Divide
- Mutations that increase number of
receptors on cell surface amplify the
division signal.
 Relay Switch
- Passage of signal into the cell’s interior.
 Relay switch stuck in “ON” position.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Curing Cancer
Amplifying the Signal
- Amplification of signal within cytoplasm.
 Releasing the Brake
- Used to restrain cell division.
 Checking Readiness
- Ensures DNA is undamaged and ready
to divide.
 Stepping on the Gas
- Restore telomerase inhibitor.

Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Curing Cancer
•
Preventing the Spread of Cancer
 Tumor Growth
- Angiogenesis Inhibitors
 Metastasis
- Cells break off and migrate.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Overview of Recombination
•
•
•
Genetic Recombination represents an
alteration in the genomic location of a gene, or
a gene fragment.
Gene Transfer - One chromosome or genome
donates a segment to another chromosome or
genome.
Reciprocal Recombination - Two
chromosomes trade segments.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Gene Transfer
•
•
Plasmid Creation
 All cells have recombination enzymes that
can cause double duplexes to undergo
reciprocal exchange.
- Loop is freed from rest of DNA and
becomes a plasmid.
Integration
 Region of plasmid DNA involved in original
exchange, recognition site, aligns with
matching sequence on main genome.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Gene Transfer
•
Conjugation
 Bacteria have genes encoding protein
subunits that assemble on the surface of
the bacterial cell, forming a pilus.
- Rolling Circle Replication
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Gene Transfer Between Bacteria
Copyright © McGraw-Hill Companies
Permission required for reproduction or display
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Gene Transfer
•
Transposition
 Transposons encode transposase enzyme
that inserts transposon into genome at a
random site.
- Causes insertional inactivation.
- Facilitates gene mobilization.
 Transposition can rapidly generate
composite plasmids (resistance transfer
factors).
- Antibiotic Resistance
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Reciprocal Recombination
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•
•
Crossing Over
 Exchange between non-sister chromatids.
Unequal Crossing Over
 Crossover between regions similar, but not
homologous, in nucleotide sequence.
Gene Conversion
 Alteration of one homologue by cell’s error
detection and repair system.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Trinucleotide Repeats
•
Trinucleotide repeat is a change in the
genetic material producing an increase in the
number of copies of repeated trinucleotide
sequences.
 Root cause of large number of inherited
human disorders.
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Classes of Eukaryotic DNA
•
DNA That Codes for Protein
 Four Classes: (1% of Human Genome)
- Single-Copy Genes
- Segmental Duplications
- Multigene Families
- Tandem Clusters
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Classes of Eukaryotic DNA
•
Noncoding DNA
 Introns (Noncoding DNA with Genes)
- 24% of Human Genome
 Structural DNA
- 20% of Human Genome
 Repeated Sequences
- 3% of Human Genome
 Transposable Elements
- 45% of Human Genome
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Review
•
•
•
•
•
•
•
•
Mutations
Changes in Gene Position
Cancer
Recombination
Gene Transfer
Reciprocal Recombination
Trinucleotide Repeats
Eukaryotic DNA
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies
Copyright © McGraw-Hill Companies Permission required for reproduction or display
Raven - Johnson - Biology: 6th Ed. - All Rights Reserved - McGraw Hill Companies