Download Chapter 13 Mutations (2)

MUTATIONS
Changes in DNA that affect genetic
information
Mutation
change in the genetic
material of a cell
Germ Cell
Mutations
occur in sex
cells and
are passed
on to
offspring
Somatic
Mutations
take
place in
body cells
Types of Mutations
 Gene mutations result from
changes in a single gene.
 Chromosomal Mutations
involve changes at
chromosome level.
 Point Mutations – Changes
in one or a few nucleotides
Point Mutation: Base Substitution
G
DNA
T
A
C
G
C
A
T
G
G
mRNA
A
U
G
C
G
U
A
C
C
Amino Acids
methionine
isoleucine
C
arginine
threonine
Mutations: Substitutions
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCACCTCACGCCA
↓
CCAGUGGAGUGCGGU
↓
Pro-Arg-Glu-Cys-Gly
• Substitutions will only affect a single codon.
• Their effects may not be serious unless they affect an amino acid that is
essential for the structure and function of the finished protein molecule.
Substitution: No change
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTTCTCACGCCA
↓
CCAGAAGAGUGCGGU
↓
Pro-Glu-Glu-Cys-Gly
A mutation may have no effect on the phenotype.
Changes in the third base of a codon often have no effect.
Example: CTC and CTT both code for Glutamine (Glu).
Substitutions: Disaster
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTCCTCACTCCA
↓
CCAGAAGAGUGAGGU
↓
Pro-Glu-Glu-STOP
Point Mutation: Frameshift
Mutation
 Inserting or deleting a
nucleotide causes the entire
code to “shift.”
 Insertion
 THE FAT CAT ATE THE RAT
 THE FAT CAT XAT ETH ERA T
 Deletion
 THE FAT CAT ATE THE RAT
 THE FAT CAT ATE THR AT
T
DNA
mRNA
T
A
C
G
C
A
T
G
G
A
U
G
A
C
G
U
A
C
C
Amino Acids
methionine
isoleucine
arginine
alanine
threonine
tyrosine
Example of Frameshift
Mutation
Mutations: Insertions
Addition of a nucleotide causes a frame shift mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Addition mutation
GGTGCTCCTCACGCCA
↓
CCACGAGGAGUGCGGU
↓
Pro-Arg-Gly-Val-Arg
Mutations: Deletions
A frame shift mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Deletion mutation
GGTC/CCTCACGCCA
↓
CCAGGGAGUGCGGU
↓
Pro-Gly-Ser-Ala-Val
Gene Mutations
 Frameshift Mutations – Shifts
the reading frame of the
genetic message
 so that the protein may not be able
to perform its function.
 INSERTION
 THE FAT CAT ATE THE RAT
 THE FAT HCA TAT ETH ERA T
 DELETION
H
 THE FAT CAT ATE THE RAT
 TEF ATC ATA TET GER AT
H
Chromosomal Mutations
 Deletion: Part of a chromosome is
deleted
 Duplication: Part of a chromosome is
duplicated
 Inversion: Chromosome twists and
inverts the code.
 Translocation: Genetic information is
traded between non-homologous
chromosomes.
Types of Chromosome
Mutations
1. Deletion
occurs
when a piece
of a
chromosome
breaks off
X
X
2. Duplication
Occurs when a gene sequence is
repeated.
2. Inversion
occurs when a piece breaks
from a chromosome and
reattaches itself to the
chromosome in the reverse
orientation
Deletion in
Chromosome 16
3. Translocation
Switch
occurs when a broken piece
of a chromosome attaches to a
non homologous chromosome
Philadelphia
Chromosome
Philadelphia
Chromosome
https://www.youtube.com/watch?v=PNgLK2XuQXc
What Causes Mutations?
 DNA can become mutated
 1. Mutations can be inherited
 Parent to child
 2. Mutations can be acquired
 Environmental agents (mutagens)
 Pesticides
 Tobacco
 UV radiation
 Nuclear radiation
 Mistakes when DNA is copied
Significance of Mutations
• Most are neutral
• Eye color
• Birth marks
• Some are harmful
• i.e. Down Syndrome
• Some are beneficial
• Sickle Cell Anemia to Malaria
• Immunity to HIV
• Evolution - Genetic variability
Objectives:
1. Describe gene regulation in
prokaryotes.
2. Explain how most eukaryotic genes
are regulated.
3. Relate gene regulation to
development in multicellular
organisms.
Prokaryotic Gene Regulation
 Prokaryotes regulate their
activities using only those
genes necessary for the cell
to function.
 OPERON: Group of structural
and regulating genes that
function as a single unit.
Prokaryotic
Gene Regulation
 Operons are composed of 4 components:
 Regulator gene: Codes for a DNA binding protein known as
a repressor (prevents RNA polymerase from binding to DNA.
 Promoter: Region of DNA where RNA polymerase attaches
to signal the start of transcription.
 Operator: Turns transcription on or off by either allowing
RNA polymerase to attach to the promoter or not.
 Structural genes: Group of 3 genes that code for enzyme
or proteins.
The Lac Operon
 When E. Coli (bacteria) is denied glucose
and given the milk sugar lactose instead, it
immediately begins to make the 3 enzymes
needed to metabolize lactose.
 The 3 structural genes that code for these
enzymes are next to each other on the
DNA strand and are under the control of a
single promoter and a single operator.
The Lac Operon – Lactose Absent
 When lactose is absent, the regulator gene codes for a
repressor that binds to the operator.
 This prevents RNA polymerase from binding to the
promoter.
 Transcription for the enzymes needed to digest lactose does
not take place. (It is unnecessary to waste the energy)
The Lac Operon – Lactose Present
 When lactose is present, the lactose molecules bind to the
repressor, changing the shape of the repressor.
 The repressor molecule cannot bind to the operator,
therefore, RNA polymerase CAN bind to the promoter and
transcription does take place.
 The enzymes needed to digest lactose are created.
Prokaryotic Regulation
Eukaryotic Regulation
 Unlike prokaryotic
cells, a variety of
mechanisms regulate
gene expression in
eukaryotic cells:
1. Chromatin structure
2. Transcriptional control
3. Translational control
Eukaryotic Regulation
 CHROMATIN STRUCTURE:
Chromatin packing is used as a
way to keep genes turned off.
 If genes are not accessible to
RNA polymerase, they cannot be
transcribed.
 In the nucleus, highly condensed
chromatin is not available for
transcription, while more loosely
condensed chromatin is
available for transcription.
Eukaryotic Regulation
 TRANSCRIPTION FACTORS: DNAbinding proteins that help initiate
transcription.
 Transcription factors control the
expression of genes (determine whether
the gene should be shut off or turned on).
Eukaryotic Regulation
 TRANSLATIONAL
CONTROL: Occurs in the
cytoplasm and affects when
translation begins and how
long it continues.
 Example: Some mRNAs
may need further processing
before they are translated.
Cell Specialization
 Eukaryotic cells have copies of
all genes, however, different
genes are expressed in
different types of cells.
 Example: Muscle cells have a
different set of genes that are
turned on than nerve cells.
 Complex gene regulation in
eukaryotes is what makes
specialization possible.
RNA Interference
Greg Hannon, PhD.
Cold Spring Harbor
Thomas Tushl, PhD.
Professor at Rockefeller
RNA Interference (micro RNA)
 Cells contain lots of small
RNA molecules
 don’t belong to any of the
major groups of RNA (mRNA,
tRNA, or rRNA).
 These small RNA
molecules
 play a powerful role in
regulating gene expression by
interfering with mRNA.
RNA Interference
 MicroRNA (miRNA), are small
RNA molecules
 regulate gene expression.
 miRNA attach to certain
mRNA molecules
 prevent translation from occurring.
RNA Interference
 Blocking gene expression by means of
an miRNA silencing complex is known
as RNA interference (RNAi).
The Promise of RNAi Technology
 RNAi has made it possible
to switch genes on and off
by inserting double-stranded
RNA into cells.
The Promise of RNAi Technology
 RNAi technology may allow
medical scientists to turn off
the expression of genes
 Cancer related diseases
may be treated.
Genetic Control of Development
 Gene expression shapes embryo
development.
 Every cell has the same genes,
however, transcription factors and
repressors determine which gene
is turned on depending on the
type of cell it is supposed to
differentiate into.
 The process of cells becoming
specialized in structure and
function is called differentiation.
Homeotic Genes: “Master Control Genes”
 Control the identities of
body parts in the
embryo
 Regulate organs that
develop in specific
parts of the body.
Homeobox and Hox Genes
 Homeotic genes share a very similar 130base DNA sequence, which was given the
name homeobox.
 Homeobox genes code for transcription
factors that activate genes that are
expressed in certain regions of the body.
 They determine factors like the presence of
wings or legs.
Homeobox and Hox Genes
 A group of homeobox
genes known as Hox
genes are located side by
side in a single cluster.
 Hox genes determine the
identities of each segment
of an animal’s body.
 Hox genes tell the cells of
the body how to
differentiate as the body
grows.
Homeobox and Hox Genes
 The colored areas on the fly
show the approximate body
areas affected by genes of
the corresponding colors.
 A mutation in one of these
genes can completely
change the organs that
develop in specific parts of
the body.
 Clusters of Hox genes exist
in the DNA of other animals,
including humans.
Environmental Influences
 Environmental factors like
temperature, salinity, and nutrient
availability can influence gene
expression.
 Example: The lac operon in E. coli
 Metamorphosis is another
example of how organisms can
modify gene expression in
response to their environment.
 Example: Unfavorable conditions may
force a frog to undergo
metamorphosis faster than usual.