Presentasi Mutasi (171111).ppt

8/11/2019 Presentasi Mutasi (171111).ppt

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MUTASI MUTATION)


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The flow of information within a cell involves the transcriptionof DNA to mRNA and the translation of mRNA to protein?

The flow of information between cell generations involves DNAreplication and distribution to two equal daughter cells?

A change in DNA to be replicated and passed on to future

generations and to effect protein structure and function if thechange occurred in the gene that coded for that protein?

The cause and effect of changes in DNA?

These changes are called mutations


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Mutations

Any change in the DNA sequence of anorganism is a mutation

Mutations are the source of the alteredversions of genes that provide the rawmaterial for evolution.


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Mutations are Random

A central tenet of biology is that the flow ofinformation from DNA to protein is one way.DNA cannot be altered in a directed way bychanging the environment. Only random DNAchanges occur.


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The simplest mutations are base changes, where one baseis converted to another. These can be classified aseither: transitions, where one purine is changed to another purine (A -

> G, for example), or one pyrimidine is changed to anotherpyrimidine (T -> C, for example).

transversions, where a purine is substituted for a pyrimidine,

or a pyrimidine is substituted for a purine. For example, A -> C. Another simple type of mutation is the gain or loss one or

a few bases.

Larger mutations include insertion of whole newsequences, often due to movements of transposable

elements in the DNA or to chromosome changes such asinversions or translocations.

Deletions of large segments of DNA also occurs.

Types of DNA Change


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Types of Mutation

Mutations can be classified according to their effectson the protein (or mRNA) produced by the gene that ismutated.

Point Mutations

Frameshift Mutations


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Point Mutations

Point mutations are the most common type of mutation.A single point mutation, also called a base substitution, occurswhen a single nucleotide is replaced with a different nucleotide.

A point mutation results in a base pair substitution afterreplication and possibly a mutant protein after transcriptionand translation.

There are three types of point mutations:

Silent mutation Missence Mutation

Nonsense Mutation


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Silent Mutation

A silent mutation causes no change in the activity of theprotein.

A silent mutation is usually the result of a substitution

occurring in the third location of the mRNA codon. Third basechanges often have no effect on the amino acid sequence of theprotein.

The genetic code is degenerate (most amino acids are coded for

by several alternative codons), the resulting new codon may stillcode for the same amino acid.

These mutations affect the DNA but not the protein. Theyhave no effect on the organisms phenotype.


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Missence Mutation

A missence mutation is a nucleotide substitution thatchanges a codon so that it codes for a differentamino acid in the protein.

Some missense mutations have very large effects,while others have minimal or no effect. This usuallyresults in a change of the activity of the protein. Thechange may be harmful or beneficial to the protein.It depends on where the mutation occurs in the

proteins structure, and how big a change in the typeof amino acid it is.


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Nonsense Mutation

A nonsense mutation is the same as a missensemutation except the resulting codon codes for aSTOP signal.

The result is a premature termination of translation.

The protein is shorter than usual and does not

contain all the amino acids that it should. Therefore,this protein is most likely nonfunctional.


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Frameshift Mutations

Another type of mutation is a frameshift mutationwhich is caused by the insertion or a deletion of abase pair.

An inserted or deleted nucleotide alters the tripletgrouping of nucleotides into codons and shifts thereading frame so that all nucleotides downstreamfrom the mutation will be improperly grouped.

The result is a protein with extensive missenseending sooner or later in nonsense.


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What causes mutations?

A mutation can be the result of different events.

Errors made during replication, repair, or

recombination can all lead to point or frameshiftmutations. Mutations resulting from such errors arespontaneous mutations.


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DNA replication is very accurate, but DNA polymerase is not100% accurate. Mutations that are not due to external factorsare called spontaneous mutations.

Our body temperature (37o

C) increases the rate of spontaneousmutation. The base C spontaneously converts to the base Ureadily at high temperatures.

A CG base pair can become a UG base pair. If the mismatch is

not detected and repaired before DNA replication begins, the Uwill be paired with an A during replication. The UG will thusbecome an UA and a CG base pair. Replacement of the U orfurther replication will result in the UA becoming an TA basepair. So, heat causes CG base pairs to become TA base pairs.

What causes mutations?


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Environmental factors also influencethe rate of mutation

A mutation can also result from the action ofphysical and chemical agents known as mutagens. Wewill now explore three mutagens: nitrous acid, baseanalogs, and UV light.


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Nitrous Acid (HNO2)

Nitrous acid affects DNA complementation.

The acid randomly modifies the base adenine so that it will pairwith cytosine instead of thymine. HNO2causes GC base pairs to

become AT base pairs, and AT base pairs to become GC basepairs

This change is made evident during DNA replication when a newbase pair appears in daughter cells in a later generation.

The salt of nitrous acid (nitrite) can be found in preservedmeats and is mutagenic.


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Nitrous acid (HNO2)


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Base Analog

A base analog is a compound sufficiently similar to one of thefour DNA bases but have different pairing properties.

For example, 5-bromouracilis the analog of thymine but

sometimes pairs with guanine and 2-aminopurineis the analog ofadanine but sometimes pairs with cytosine. It can beincorporated into DNA and pair with A or G. It results in AT toGC changes or GC to AT changes

The incorporation of a base analog will to a base pairsubstitution in that appears in daughter cells in a latergeneration.


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5-Bromouracil


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X-rays & UV Light

Ionizing radiation (X-rays) & nuclear radiation causemutations by creating highly reactive free radicalscan cause minor or major mutations. They can reactwith DNA and cause breaks in the DNA backbone.

This may destroy individual genes, or result in loss ofwhole sets of genes through loss of pieces ofchromosomes.

UV rays from sunlight result in the formation of TTdimers


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UV Light


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UV Light

Exposure to direct UV light induces covalent linking betweenadjacent thymine nucleotides on a DNA strand forming athymine dimer.

These dimers cause the strand to buckle, disrupting normal basepairing. This prevents proper replication and transcription.

Bacteria have enzymes to fix the damage created by UV light.

An enzyme cuts the DNA at two point and removes the damagedportion.


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UV Light

T-T dimers can be repaired, but if they remain unrepaired untilreplication, the opposite strand will be replicated incorrectly.DNA polymerase will skip the bases included in the dimer, and a2 nucleotides will be lost from the DNA.

DNA polymerase synthesizes a new DNA segment using thehealthly strand as a template.

DNA ligase joins the new fragment to the old strand.


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Mutation Rate

Mutations are random events and there is no way ofknowing when a mutation will occur.

Genes do, however mutate spontaneously at acharacteristic rate, making it possible to assignprobabilities to certain mutation events.

The probability that a gene will mutate when a celldivides is called the mutation rate.


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Mutation Rate

Spontanoeus mutation rate for the average gene is0.000000001.

This means a mutation event is estimated to occuronce in every million genes replicated.

The presence of a mutagen increases the rate ofmutation to 0.00001 to 0.001.

This means that a mutation event is estimated tooccur once in every hundred thousand to onehundred thousand genes in the presence of amutagen.


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Alleles of a gene commonlydiffer by only a single nucleotide

pair in DNA. The nucleotide

change results in an amino acidchange in the protein and achange in the properties of the

protein.


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Sickle-cell anemia

Sickle-cell anemia is due to a recessive gene.Homozygotes for the sickle-cell allele have sickle-cell anemia. They have problems delivering oxygen totheir tissues when they are stressed and oxygen

levels in their blood start to drop.

The gene codes for Hb, one of the twoproteinsthat make up the hemoglobin 2 molecule.


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A single base-pair change in DNA canaccount for the amino acid change

HbS, sickle cell hemoglobin, is a change in the beta-globin gene, where a GAG codon is converted to GUG.GAGcodes for glutamic acid, which is a hydrophilic

amino acidthat carries a -1 charge, and GUG codesfor valine, a hydrophobic amino acid. This amino acidis on the surface of the globin molecule, exposed towater. Under low oxygen conditions,valinesaffinity for hydrophobicenvironments causes the hemoglobinto crystallize out of solution.


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-Hb has an amino acid sequence containing 146 amino acids.

In normal -Hb, the sixth amino acid is GLU

In sickle-cell -Hb, the sixth amino acid is VAL

in mRNA:

GLU is coded by either GAA or GAG

VALis coded by GU_

Normal Sickle cellanemia

Template: ... CTT ... ... CAT ...

Coding: ... GAA ... ... GTA ...

Codon: ... GAA ... ... GUA ...

Aminoacid:

... GLUTAMICACID ...

... VALIN ...


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All genetic variation arises from changein the nucleotide sequences of DNA


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Presentasi Mutasi (171111).ppt