Genetic Mutation

Report
Suppose that eye gene is sex linked,
and wing is autosomal. A red eyed
female, long wing is crossed to a
male with yellow eyes, vestigial
wings. Diagram the cross if the
female is heterozygous for both
traits.
Mutations
-Gene Mutation
- Chromosome Mutation
Compiled by Siti Sarah Jumali
Room 14, Level 3
06-4832123
5 Ways of Creating Genetic Diversity in
Bacteria
A.
B.
C.
D.
E.
Mutations
Transformation
Conjugation
Transposition
Transduction
MUTATIONS
Mutation – any changes in the DNA sequence that
affects genetic information and the appearance of
offspring.
• Occur naturally at low level (also known as
spontaneous mutations),
during
DNA
replication ; or
• Caused by UV Light, X-Rays, mutagens error
during DNA replication by the effects of chemical
agents called mutagens; or by physical agents
like radiation.
Types of Mutations
• Gene mutation – a mutation that occurs in a
single gene and affects one trait.
Eg: Eye color, Sickle cell Anemia,
Hemophilia
• Chromosome mutation – a mutation that
occurs in many genes and affects many traits at
once.
Eg: Down Syndrome (an extra 21st
chromosome)
• Genome mutation – mutation on ploidy
1. GENE MUTATIONS
Gene Mutation
• Involve insertion or removal of 1 or more base
pairs
• Gene mutation is a change in single base pair
within DNA sequences
Effects of Gene Mutations
Most mutations are neutral - they have no effect
on the polypeptide.
Some mutations result in a less active product;
Less often an inactive product;
Very few mutations are beneficial.
Effects of Gene Mutations cont’d
• Affects molecular changes in the DNA
sequence of a gene
• Alter the coding sequence within a gene
• Causes permanent change in DNA sequence
Body (Somatic) and Gamete
(Germ)mutation
Body cell mutations can cause cancer.
- only the individual is affected.
Gamete cell mutations affect the egg and the
sperm.
- all offspring of the individual can be
affected.
In multicellular organisms (plants or animals) mutations may occur in the somatic cells of the
organism. Somatic cells are the cells involved in growth and repair and maintenance of the
organism. A mutation in these cells may lead to cancer and certain of chromosomal mutations
may be involved in aging. Other mutations happen in the germ cells and these mutations may
appear in the gametes and then in the offspring produced by sexual reproduction. These sorts of
mutations are called germ cell mutations.
Types of Mutations
1. Point mutations - a one base change in
DNA.
2. Frame Shift Mutations - the addition or
deletion of 1 or more bases. These are due to
powerful mutagens; chemical or physical.
Normally..
DNA (antisense strand)
mRNA
Polypeptide
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
The antisense strand is the DNA strand which acts as the
template for mRNA transcription
© 2010 Paul Billiet ODWS
The amino acid chart
The amino acid chart with diseases
1. Point Mutation
3 types:
a. silent mutation - single base substitution in the 3rd
base nucleotide position of a codon. This
results in NO change in amino acid. Note that the
first 2 letters of the genetic code are the most
critical.
b. missense mutation - single base substitution in 1st or
2nd base nucleotide position. This results in
changed amino acid.
c. nonsense mutation - single base substitutions that
yield a stop codon. Note: there are 3 nonsense
codons in the genetic code = NO PROTEIN
Silent or neutral mutation
• Silent mutation can result in enhancing new
protein, but all other mutations reduce the
function
Silent
mutation
Missense
mutation
Nonsense
mutation
2. Frameshift Mutations
Additions
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS
Addition mutation
GGTGCTCCTCACGCCA
↓
CCACGAGGAGUGCGGU
↓
Pro-Arg-Gly-Val-Arg
2. Frameshift Mutations cont’s
Deletion
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS
Deletion mutation
GGTC/CCTCACGCCA
↓
CCAGGGAGUGCGGU
↓
Pro-Gly-Ser-Ala-Val
Frameshift mutation
Frameshift
mutation
Mutations Can Be Neutral
• They may have little or no effect on the survival of an
organism or on its ability to reproduce.
• They may result in the same kind of organism meaning that the change still tells the cell to do what
it should, so there is no difference.
• It is estimated that the average human has 50-100
mutations within their DNA - most (if not all) are
neutral or beneficial
Mutations Can Be Beneficial
• Bacterial resistance to antibiotics
• Insecticide resistance in bugs
• Rapid mutation rates in virus’s proteins
allowing them to adapt to new “hosts”
Mutations Can Be Beneficial
• In humans, it can be a different set of
circumstances… Here’s an example:
• Sickle-Cell Anemia is a genetic disorder in which
there is a defect in the structure of red blood cells.
This leads to fatigue and anemia when not treated.
• However, it has been found that people who are
carriers for Sickle-Cell Anemia also has some
genetic protection against another disease,
malaria.
Mutations Can Be Beneficial
• In evolutionary studies, scientists have connected
the presence of a brain chemical microcephalin (a
proposed mutation) with the human’s development
of art, music, and complex tool-making practices
• This same research indicates that the human brain
is still evolving and becoming more and more
capable of more complex tasks
• Some humans have been found to have mutations
that protect them from other diseases, such as
AIDS
Compare the following types of base-substitution mutation.
Mis-sense
mutation
Silent mutation
Number of bases
substituted
1
Stop codon
produced early –
polypeptide
shortened
Effect on
polypeptide
Example illness
Nonsense
mutation
Sickle cell disease
mRNA
amino acid
Self-Quiz
• Describe the effects of sickle cell disease on
sufferers in terms of:
• Hemoglobin production
• Symptoms and mortality
• Identify parts of the world where a single
sickle cell (Hbs) allele could be beneficial
2. CHROMOSOME MUTATION
Chromosome Mutation
Chromosome structure become influenced by
1. Change in amount of genetic information in
chromosome because of
– Deletion
– Duplication
2. Similar amount of genetic information but the
materials are rearranged
– Inversion
– Translocation
Chromosome Mutation cont’d
• Deletion
– Loss of chromosomal segment
• Duplication
– Repetition of chromosomal segment
• Inversion
– A change in the direction of the genetic material along a single
chromosome
• Translocation
– A segment of one chromosome becomes attached to a different
chromosome
– Simple translocation
• One way transfer
– Reciprocal translocation
• Two way transfer
Duplications
• Insertion of an extra copy of a region of a
chromosome into a neighboring position.
• Zygotes produced from gametes involving
duplications are often viable and may or may not
have any serious problems.
• Various sorts of duplications are related to color
vision conditions many of which are quite subtle
in their effects e.g certain anemias involving
abnormal hemoglobins called the thalassemias.
Deletions
• Deletions result when a gene is mistakenly
removed from a chromosome, as a result
of unequal crossing over.
• Often zygotes produced by gametes involving
deletions are not viable since they do not have
the full compliment of genes.
Inversions
• Inversions happen when a whole region of genes on a
chromosome gets flipped around .
• 2 types of inversions.
– paracentric inversions the centromere is not included in the
inversion.
– pericentric inversions, the centromere is involved in the
inversion.
Both these types of inversions lead to abnormalities in
crossing over and meiosis resulting in some chromosomes
which are not viable, while others are viable but have new
combinations of genes. These sorts of inversions are thus
important in reshuffling genes on a chromosome.
Translocations
• Movement of part of a chromosome to another
part of the genome.
• May happen with the same chromosome.
– translocation is an intrachromosome translocation.
Other translocations involve transfer of a region of a
chromosome to a non homologous chromosome. For
example certain types of Down syndrome involve
translocations between chromosome 14 and
chromosome 21. This type of translocation between
non homologous chromosomes is called an interchromosomal translocation.
• Base substitution changes is in pair
• 2 types of changes
– Transition (within same group AT and GC)
– Transversion (between 2 groups)
Transition vs Transversion
Inversion mutation
Inversion mutations, also, only affect a small part of the gene
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
© 2010 Paul Billiet ODWS
Inversion mutation
GGTCCTCTCACGCCA
↓
CCAGGAGAGUGCGGU
↓
Pro-Gly-Glu-Cys-Gly
GENOME MUTATION
Changes in chromosome number
•
•
•
•
Aneuploidy
Polyploidy
Autopolyploidy
Allopolyploidy
Aneuploidy
• Normally 2N ends up either with extra copies of homologous
chromosomes or fewer than the normal diploid number.
• Happens when homologous chromosomes fail to segregate properly during
meiosis (non disjunction).
• Monosomy (2n-1) in which the diploid individual has only one member of
a certain homologous chromosome.
• The other common type of aneuploidy is called trisomy (2n+1) because the
individual has three copies of the chromosome.
Aneuploidy leads to a number of syndromes in humans. For example
trisomy 21 leads to Down syndrome, characterized by mental retardation
and other abnormalities. Aneuploidy involving the sex chromosomes is
common. XYY males are normal but XXY males and XXXY males have a
syndrome called Klinefelter syndrome. These males are often actually
intersexed or hermaphroditic with partially developed sexual organs of both
genders. These individuals are sterile and are often subjected to hormones
and surgery to bring them into conformance with social gender roles.
Polyploidy
•
•
•
•
•
3N or sets of chromosomes in a nucleus.
Can happen because of a failure of the spindle fibers in mitossis or meiosis to segregate chromosomes
into separate groups.
Many organisms have specialized polyploid tissues even organisms we typically consider as diploid.
– For example in plants a so called double fertilization leads to the genesis of a diploid zygote from
the union of two gametes produced by the haploid gametophytes, but also a specialized triploid
tissue (3N) called endosperm. This tissue is produced when a male gamete fertilizes special diplid
tissue from the flower. In mammals, cells of the liver are typically polyploid.
Believed to be an important mechanism in the development of new species and a common pattern in
plants is to find populations of two species both of which might be diploid. Where the species overlap a
series of localized polyploid populations are often found. These polyploid populations are often
effectively reproductively isolated from the parent species and thus can be considered species in their
own right.
E,g plant species and some fish and amphibians;
– domestic wheat is hexaploid(6N). ‘
– Seedless' plants are usually triploid (3N).
Consider a tetraploid plant (4N). The gametes of this plant are going to be effectively diploid (2N)
and if they are fertilized by a normal haploid gamete (N), the result is a triploid plant. Since triploid
plants have an odd number of chromosomes, typically the gametes have variable number of
chromosomes are usually not viable. This is why triploid plants are used to produce seedless
plants. Since most plants can self fertilize, the tetraploid plant can breed with itself and produce
viable tetraploid populations.
Autopolyploidy
• Autopolyploidy is polyploidy in which all the
chromsomes originate from the same diploid
parent species. Domestic banana and various
seedless plants are often triploid
autoployploids.
Allopolypoidy
• Allopolypoidy is a polyploidy in which the sets of
chromosomes are from differrent species. Usually
hybrid plants (N1 + N2) from such crosses are not
fertile since proper pairing of chromsomes does not
occur in meiosis. But sometimes the the chromosome
number spontaneously doubles leading to tissues with
2N1 + 2N2. If this tissue is germ tissue, tissue that can
give rize to haploid tissue via meisosis the result can be
gametes with the N1 + N2 chromosome complement.
When two of these gametes fuse, the result is an
allopolyploid plant with a viable chromosome
complement (2N1 + 2N2).
Factors that causes mutation
A. Chemical mutagens - used in research to study mutagenesis.
There are 3 kinds of chemical mutagens.
1. Alkylating agents. Adds alkyl group, CnH(2n+1)
Eg. formalin, nitrogen, mustard, and ethylene oxide (reacts with
G changing it to bind with T).
2. Base analogs. Mimics a nitrogen base. Ex. AZT is a modified
sugar that substitutes for T. Eg. 5 - bromouracil binds with A or
G.
3. Intercalating agents. Inserts into DNA and pushes bases
apart. Eg. AFLATOXIN - a chemical produced by peanut and
grain molds. The mold is Aspergillus flavus (fungus).
B. Physical mutagens:
1. nonionizing radiation - Causes the
formation of T= T dimers. UV light @ 260
nm.
2. Ionizing radiation - damages DNA by
causing the formation of “free radicals”
leading to mutations. 3 Ex. X-rays. Gamma
rays from radioactive fallout penetrates the
body. Alpha rays from inhaled dust
containing radioactive fallout.
TRANSFORMATION
B. TRANSFORMATION
The passage of homologous DNA from a dead
donor cell to a living recipient cell. Occurs in
Streptococcus pneumoniae. When S. pneumo
dies the DNA can be absorbed by a living S.
pneumo and recombined into the chromosome.
The gene for capsule formation is obtained in
this way, as is a gene for penicillin resistance.
Discovered in 1929 by Fredrick Griffith.
GA sp07
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Griffith’s Transformation Experiment
C. CONJUGATION
1. A “mating” process between a donor
F+ (bacteria with fertility factor =plasmid)
and an F- recipient cell.
2. Occurs in Gram - enteric bacteria like
E.coli
3. Discovered in 1946 by Joshua Lederberg
and Edward Tatum.
4. Plasmids carry genes that are nonessential
for the life of bacteria. Ex. gene for pili (sex
pilus). Ex. plasmid replication enzymes.
Ex. Medical Problem: R-Factor = antibiotic
resistance!
Conjugation continued
“Normal - Sex” plasmid transfer
(usually ~20 of 100 genes).
a. Requires a sex pilus
b. F + bacteria transmits a copy of the
plasmid
to F- bacteria. This converts the F- cell into an F +
cell. Medical Problem: The R factor (antibiotic
resistance) on the F factor is transmitted!
http://www.cat.cc.md.us/courses/bio141/lecguide/uni
t4/genetics/recombination/conjugation/f.html
6. Hfr (High Frequency Recombination)
a. Hfr- bacterial plasmid integrates into the
chromosome.
b. Medical Problem: Hfr antibiotic resistance
genes are passed during binary fission
(every time the cell divides). Therefore,
antibiotic resistance spreads very rapidly!
c. When Hfr mate with F – bacteria, only the
bacterial genes cross NOT plasmid genes.
Genetic diversity results in this case due to
recombination.
http://www.cat.cc.md.us/courses/bio141/lecguid
e/unit4/genetics/recombination/conjugation/hfr.
html
•
D. TRANSPOSITION p 285
1. Transposons (jumping genes) are big
chunks of DNA that randomly excise
and relocate on the chromosome.
2. Transposons were discovered in 1950 by
Barbara McLintock in corn.
3. Causes antibiotic resistance in Staph.
aureus, the famous methicillin
resistant Staphlococcus aureus (MRSA)
strain!
E. TRANSDUCTION
the transfer of genetic material from
donor bacteria to recipient bacteria via a
transducing agent (virus!). Bacterial
viruses are called bacteriophage.
1. Discovered in 1952 by Zinder &
Lederberg.
2. Two kinds of transduction:
generalized and specialized.
•
2. Generalized transduction: Starts with the
LYTIC CYCLE where a T- even phage (Fig.
8.5 pg 210) infects E.coli killing the host cell,
and synthesizing 2,000 copies of itself. The
T-even phage randomly packages bacterial
DNA in a few defective phages. Once a T –
even phage infects another E. coli, this
genetic information can be recombined into
the host cell without causing the lytic cycle.
New genetic information is thereby
transduced from one bacteria to another.
Generalized Transduction
•
•
Generalized
Transduction
Specialized Transduction
3. Specialized transduction
Lambda phage infects E.coli. The phage does not
lyse the cell immediately. Instead it integrates
into chromosome of the bacteria as a prophage
and remains dormant. This is called the
LYSOGENIC CYCLE.
Phage genes are
replicated and passed to all daughter cells until
the bacteria is under environmental stress,
from lack of nutrients, etc. Then phage gene
will excise from the nucleoid and enter the
LYTIC CYLE taking one adjacent gene for
galactose metabolism.
Specialized Transduction Cont.
The gal transducing phage (lambda)
makes ~ 2,000 copies of itself with the gal
gene, and infects other E.coli. When gal
integrates into the nucleoid of other E.
coli, it may provide these bacteria with a
new capacity to metabolize galactose.
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Comparison of Bacteriophage
3. Comparison of bacteriophage
transduction in E.coli.
Generalized
Specialized
T even phage
lambda phage
lytic cycle
lysogenic
random packaging
specific gal gene
End of Slides

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