Wh at is M u tation ?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. 2
With ou t M u tation •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 3
D N A S e qu e nce s At molecular level, mutations are alteration in the DNA molecules. Chromosomes can exchange parts & genetic material can even jump from one to another chromosomes 4
S om atic M u tation •Somatic mutation •Germline mutation 5 Cancer
G e rm line M u tation 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 6
C las s ification There are different ways of classifying mutation Functionally Structurally Nonsense Point Missense Frameshift Silent Harmful Neutral Beneficial 7
H arm fu l m u tation 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. 8
Be ne ficial M u tation •Ultimate source of all genetic variation •Raw material for evolution •able to evolve & adapt to environmental changes For example •Protection against HIV infection 9
N e u tral M u tation 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. 10
S tru ctu rally Point Nonsense Frameshift Missense 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
S tru ctu rally DNA structure permits some basic type of alteration or mutation at a site. Point mutation can be categories as Transition Deletion Transversions Insertion Translocation Inversion 12
P oint M u tation 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 . 14
P oint M u tation Replacement of a Purine base with another Purine or pyrimidines with another pyrimidines Replacement of a purine with pyrimidines or vice versa 15
P oint M u tation A point mutation can also change a codon so that a different protein is specified, a non synonymous change. For example Sickle Cell disease 16
D N A s tru ctu re 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 17
Sense mutations are the opposite of nonsense mutations. Here, a stopcodon is converted into an amino acid codon. Since DNA outside ofprotein-coding regions contains an average of 3 stop codon per 64, thetranslation 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. 18
P oint m u tation 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
A mutation can occur spontaneously or be induce by chemicals or radiationSpontaneous 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,
Replacement of a Purine base with another Purine or pyrimidineswith another pyrimidinesReplacement of a purine with pyrimidines or vice versa 22
Induced mutation are those resulting from exposure of organism to mutagenicagents 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
Radiation e.g., X-rays, UVIonizing radiation breaks covalent bonds including those in DNA and is theleading cause of chromosome mutations. Ionizing radiation has a cumulativeeffect and kills cells at high doses.UV (254-260 nm) causes purines and pyrimidines to form abnormal dimerbonds and bulges in the DNA strands.
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 carryout 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.
P re p are d B y ZAH ID A U MAR B .S c H ons, 5th se m e te r 387-B H -07D e p t of E nvironm e ntal S cie nce s 27