1DNA structure

What is Mutation?

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Sudden heritable changes in genetic material is know as Mutation

The term Mutation refers both to •Change in genetic material &.

•To the process by which the change occurs.

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Without Mutation

•All genes would exist in one form

•Alleles would not exist

•Genetic analysis would not be possible

•Not able to evolve & adapt to environmental changes

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DNA Sequences

At molecular level, mutations are alteration in the DNA molecules. Chromosomes can exchange parts & genetic material can even jump from one to another chromosomes

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Somatic Mutation

•Somatic mutation

•Germline mutation

Cancer

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Germline Mutation

In germline mutation, the change occurs during the DNA replication that processes meiosis. The resulting gametes & all the cells that descend from it after fertilization have the mutation

Classification

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There are different ways of classifying mutation

Functionally Structurally

HarmfulBeneficial

Neutral

PointFrameshift

Missense

Nonsense

Silent

Harmful mutation

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Mutation can cause errors in protein sequence creating non functionally proteins. Harmful mutation can cause genetic disorders

•,Drosophila melanogaster A drosophila with legs grown over the head as a result of mutation.

•A baby with an abnormal formation of eyes and eyelids because of mutation.

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Beneficial Mutation

•Ultimate source of all genetic variation

•Raw material for evolution

•able to evolve & adapt to environmental changes

For example

•Protection against HIV infection

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Neutral Mutation

A neutral mutation is a mutation that occurs in an amino acid codon but it has no impact.

A change in a base pair results in an amino acid change but the new amino acid has the same chemical properties as the old amino acid.

Point

Frameshift Missense

Nonsense

Silent

A point mutation or single base substitution, is a type of mutation that causes the replacement of single base nucleotides with another nucleotides of DNA or RNA

Structurally

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Structurally

DNA structure permits some basic type of alteration or mutation at a site. Point mutation can be categories as

Deletion

Insertion

Inversion

Translocation

Transition

Transversions

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Point Mutation

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Point Mutation

Translocation are transfer of a Piece of One chromosomes to a non homologous chromosomes

Translocation can alter the phenotype in several ways

•The break may occur within a gene destroying its function

•Translocated genes may come under the influence of different promotes and enhance so that their expression is altered

•Breakpoint may occur within a gene creating a hybrid gene.this may be transcribed & translated .

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Point Mutation

Replacement of a Purine base with another Purine or pyrimidines with another pyrimidines

Replacement of a purine with pyrimidines or vice versa

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Point Mutation

A point mutation can also change a codon so that a different protein is specified, a non synonymous change.

For example Sickle Cell disease

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DNA structure

A nonsense mutation is a genetic mutation in a DNA sequence that results in a shorter, unfinished protein product

During protein formation,DNA nucleotide sequences are read three nucleotides “Codon” & each codon corresponds to a specific amino acid or stop codon, also called nonsense codon

Thus ,nonsense mutation occurs when a premature or stop codon is introduced in DNA .When the mutated sequence is translated into a protein, the resulting protein is incomplete & shorter than normal. Most nonsense mutation result in non functional protein

Examples:

•Blood Clotting disorder

•Becker Muscular Dystrophy

•Ehlersdanles Syndrome

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Sense mutations are the opposite of nonsense mutations. Here, a stop codon is converted into an amino acid codon. Since DNA outside of protein-coding regions contains an average of 3 stop codon per 64, the translation process usually stops after producing a slightly longer protein.

Example: Hb-α Constant Spring. alpha-globin is normally 141 amino acids long. In this mutation, the stop codon UAA is converted to CAA (glutamine). The resulting protein gains 31 additional amino acids before it reaches the next stop codon. This results in thalassemia, a severe form of anemia.

Frameshift mutation is a genetic mutation caused by indels i.e., insertion or deletion of a number of nucleotides.

Due to triplet nature of gene expression by codon, the insertions or deletion can disrupt the reading frame

A Frameshift mutation causes the readings of all codon after the mutation to the different amino acids .the protein being created could be abnormally short ,long or contain the wrong amino acids.and functionless.

Example:

Tay sachas disease

Point mutation

A mutation can occur spontaneously or be induce by chemicals or radiation

Spontaneous mutations on the molecular level include:

Tautomerism - A base is changed by the repositioning of a hydrogen atom.

Depurination - Loss of a purine base (A or G).

Deamination - Changes a normal base to an atypical base; C → U,

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Replacement of a Purine base with another Purine or pyrimidines with another pyrimidines

Replacement of a purine with pyrimidines or vice versa

Induced mutation are those resulting from exposure of organism to mutagenic agents such as ionizing radiation UV light or various chemical.

Induced mutations on the molecular level can be caused by Chemicals

•Hydroxylamine NH2OH•Base analog i.e., Brdu•Alkylating agents•DNA intercalating agents e.g. ethidium bromide•DNA cross linkers•Oxidative Damage•Nitrous Acids•Acridines Dyes

Alkylating agent

5-Bromouracil

2-Aminopurine

Nitrous Acid Acridines Dyes

Proflavin

e.g., X-rays, UV

Ionizing radiation breaks covalent bonds including those in DNA and is the leading cause of chromosome mutations. Ionizing radiation has a cumulative effect and kills cells at high doses.

UV (254-260 nm) causes purines and pyrimidines to form abnormal dimer bonds and bulges in the DNA strands.

Radiation

In some genes mutation are more likely to occur in region called hotspots, where sequences are repetitive. It is as if the molecules that guide and carry out replication become confused by short repeated sequences.

For example:

More than one third of the many mutation that causes Alkaptonuria occur at or near one or more CCC repeats even though these repeats accounts for only 9% of the gene

Such a segment of DNA with identical sequences but opposite in direction is called a palindrome. A palindrome site is a sequence of base pairs in double stranded DNA that reads the same backwards and forward across the double strand.

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Prepared By ZAHIDA UMAR

B.Sc Hons, 5th semeter387-BH-07

Dept of Environmental Sciences