What are mutations?- Any changes in the DNA sequence of an organism is a mutation.- DNA is made of a long sequence of smaller units strung together. There are four basic types of unit: A, T, G, and C.- Some parts of DNA are control centers for turning genes on and off.- some parts have no function.- And some parts have a function that we dont understand yet.- Organisms have mechanisms such as DNA repair to remove mutations.
What are mutations?- Other parts of DNA are genes that carry the instructions for making proteins .- Proteins are long chains of amino acids.- These proteins help build an organism.- Protein-coding DNA can be divided into codons — sets of three bases that specify an amino acid or signal the end of the protein.
Classifications of mutations OR Types of Mutation
A- Good or bad or neutral.- A harmful mutation Is a mutation that decreases the fitness of the organism.- A beneficial mutation Is a mutation that increases fitness of the organism, or which promotes traits that are desirable.- A neutral mutation Has no harmful or beneficial effect on the organism. Such mutations occur at a steady rate, forming the basis for the molecular clock.
B- Somatic or germline
C- Spontaneous or Induced Mutations - Most mutations are spontaneous, rather than being induced by a mutagen. - Spontaneous mutation ; A mutation occurring in the absence of mutagens, usually due to errors in the normal functioning of cellular enzymes.
Spontaneous MutationsThese mutations can be caused by:• Tautomerism – A base is changed by the repositioning of a hydrogen atom, altering the hydrogen bonding pattern of that base resulting in incorrect base pairing during replication.• The ability of a molecule to exist in more than one chemical form is called tautomerism .• All the four common bases of DNA (A, G, C and T) have unusual tautomeric forms, which are rare.
Spontaneous Mutations- Depurination – In molecular genetics, depurination is an alteration of DNA in which the purine base (adenine or guanine) is removed from the deoxyribose sugar by hydrolysis of the beta-N-glycosidic link between them.- Loss of a purine base form an apurinic site (AP site). where the sugar phosphate backbone remains and the sugar ring has a hydroxyl (-OH) group in the place of the purine.
Spontaneous Mutations• Deamination – Hydrolysis changes a normal base to an atypical base containing a keto group in place of the original amine group.
Spontaneous Mutations- Slipped strand mispairing - Denaturation of the new strand from the template during replication, followed by renaturation in a different spot lead to insertions or deletions.- (SSM) is a process that produces mispairing of short repeat sequences between the mother and daughter strand during DNA synthesis
Induced Mutations• Ingredients that cause mutations are called mutagens. Mutagen is divided into three, namely:1- Mutagenic chemicals like;• Hydroxylamine NH2OH• Base analogs (e.g. BrdU)• Alkylating agents• Agents that form DNA adducts• DNA intercalating agents• DNA crosslinkers• Oxidative damage
Induced Mutations Nitrous acid converts amine groups on A and C to diazo groups, altering their hydrogen bonding patterns which leads to incorrect base pairing during replication.
Induced Mutations- Ultraviolet light is absorbed by the nucleic acid bases, and the resulting influx of energy can induce chemical changes.
Induced Mutations- The most frequent photoproducts are the consequences of bond formation between adjacent pyrimidines within one strand, and, of these, the most frequent are cyclobutane pyrimidine dimers (CPDs).- T CPDs are formed most readily, followed by T-C or C-T; C-C dimers are least abundant.
Induced Mutations3- Mutagen biological substances.suspected viruses and bakeries can cause mutations. Of the virus that can cause mutations is DNA.
D- Forward or Reverse Mutations- In an organism when mutations created a change from wild type to abnormal phenotype, then that type of mutations are called forward mutations.- Most mutations are of forward type.- The forward mutations are often corrected by error, correcting mechanism, so that an abnormal phenotype changes into wild type phenotype. Such mutations are called back or reverse mutations.
E- Point or frameshift mutations
Point mutations- Point mutations also called Single base substitutions are single nucleotide base changes in a genes DNA sequence.- It exchange a single nucleotide for another.- These changes are classified as transitions or transversions.
Point mutations- Most common is the transition that exchanges a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T).- Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G).
Point mutations- Point mutations that occur within the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for: • Silent mutations: which code for the same amino acid. • Missense mutations: which code for a different amino acid. • Nonsense mutations: which code for a stop and can truncate the protein.
Point mutationsIllustration of three types of point mutations
frameshift mutations- Frameshift mutation is a mutation caused by add or remove one or more DNA bases of nucleotides that is not evenly divisible by three from a DNA sequence.- Insertion or deletion mutations cause frameshift mutations.
frameshift mutations• Addition or deletion of one or two bases results in a new sequence of codons which may code for entirely different amino acids. This results in a drastic change in the protein synthesized.
DNA Repair• Cells have developed a number of systems designed to repair DNA damage and correct mutations.1- Photoreactivation- For Repair Thymine Dimers by A brief exposure to blue light following UV exposure can reverse the effects of the UV radiation.
DNA Repair• An enzyme called photolyase or photoreactivation enzyme (PRE), which cleaves the covalent bonds linking the thymine dimers using the energy from a DNA Repair Pathway. This flow chart shows one way that damaged photon of blue light. DNA is repaired in E. coli bacteria.
DNA Repair• 2- Base excision repair The damaged or inappropriate base is removed from its sugar linkage and replaced. These are glycosylase enzymes which cut the base-sugar bond.• 3- Nucleotide excision repair - This system works on DNA damage which is "bulky" and creates a block to DNA replication and transcription. - (UV-induced dimers and some kinds of chemical adducts). - It probably recognizes not a specific structure but a distortion in the double helix.
DNA Repair4- Recombinational (daughter-strandgap) repair- This is a repair mechanism whichpromotes recombination to fix thedaughter-strand gap--not the dimer--andis a way to cope with the problems of anon-coding lesion persisting in DNA.- Double Strand Break (DSB) Repair.Shown is an overview of the main stepsand factor requirements for DNA DSBrepair by homologous recombination (left)and non-homologous end-joining (right).
DNA Repair• Mismatch repair - This process occurs after DNA replication as a last "spellcheck" on its accuracy. - In E. coli, it adds another 100-1000-fold accuracy to replication. - It is carried out by a group of proteins which can scan DNA and look for incorrectly paired bases (or unpaired bases) which will have aberrant dimensions in the double helix. - The incorrect nucleotide is removed as part of a short stretch and then the DNA polymerase gets a second try to get the right sequence.