Genetic Mutations: Types, Causes, and Consequences in Bioinorganic Chemistry, Study notes of Inorganic Chemistry

Download Genetic Mutations: Types, Causes, and Consequences in Bioinorganic Chemistry and more Study notes Inorganic Chemistry in PDF only on Docsity! 1 5 Bioinorganic Chemistry CHEM-332 Genetic Mutations 1 5 • Mutations are considered the driving force of evolution, where less favorable (or deleterious) mutations are removed from the gene pool by natural selection, while more favorable or beneficial mutations tend to accumulate, leading to continuous evolution. • Neutral mutations are those that do not affect the organism's chances of survival in its natural environment. These mutations can accumulate over time, and can result in what is known as punctuated equilibrium which result in non-continuous evolution. Mutations 1 5 Organisms have many ways of proofreading and repairing damaged or mutated DNA. Most mistakes are repaired, however some of them are not and may lead to genetic diseases. Mutation rates also vary across species. Evolutionary Biologists have theorized that higher mutation rates may be beneficial in some situations, because they allow organisms to evolve and therefore adapting faster to their changing environment. Mutations 1 5 Causes of mutation There are two classes of mutations: spontaneous mutations which are naturally occurring, and induced mutations caused by mutagens. Spontaneous mutations At the molecular level include: Tautomerism Keto  Enol Amino  Imino Mutations 1 5 Causes of mutation Spontaneous mutations Deamination ap-site Loss of A or G; they occur 1000 times each day in mammals Deamination to base analogs is estimated to occur 100 times each day in mammals, Cytosine (C) Uracil (U), or Adenine (A)  Hypoxanthine(HX) Cytosine Uracil Mutations 1 5 • Although a point mutation is usually the change of a single nucleotide in DNA. It can also be the deletion of a single nucleotide, or just a few base pairs that affect the function of a single gene. • A point mutation can be reversed by • another point mutation, in which the nucleotide is changed back to its original state (true reversion). • a second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). Point Mutations Mutations 1 5 Point Mutations Mutations 1 5 There are several kinds of point mutations, depending upon what the erroneous codon codes for: •silent mutations: codes for the same amino acid, so it has no effect. •missense mutations: codes for a different amino acid in the protein and the protein function is affected. •nonsense mutations: results in a stop codon, which truncates the protein. •frameshift mutations: causes a shift in the reading frame, which introduces unrelated amino acids into the sequence and is usually followed by a stop codon. Point Mutations Mutations Id-type sequences amine N-Phe Arg Trp ile Ala Asn-C mANA S'-UUU CGA UGG AUA GCC AAU-3° DNA 2 -AAA GCT ACC TAT CGG TTAS' S-TTT CG4 1TGG ATAa GOl AAT a’ 3'-AS GCT ACC TAT CGG TTA-5’ 5’-TT CGA TGG ATA GCC AAT-3' N- Arg Trp Je Ala Asn-C Point aa 1 ScTT Oca Me bia. ote Bat Mutations ScTTT CGA TAG. ATA GCC AAT: ameshift by addition 3444 GCT ACC | B-TTT €GA TGG N-Phe = Arg Trp Frameshift by deletion 3’-AAA ACCT ATC GGT TA-5’ S-TTT GGA TAG CCA AT-3° N-Phe Gly Stop 1 5 • Deletion: remove one or more nucleotides from the DNA, shortens the DNA. These mutations are irreversible and they can alter the reading frame of the gene. Large Scale Mu ations • Duplication: repeats a set of nucleotides from the original DNA, resulting on a longer DNA. Like insertions, these mutations can alter the reading frame of the gene. • Inversion: reverses a segment of nucleotides from the DNA, it doesn’t alter the length of the DNA. These mutations alter the reading frame of the gene. 1 5 • When the number of nucleotides is a multiple of three, they may result is less serious consequences. • Huntington’s disease involves repeated trinucleotide CAG which inserts extra glutamins (Gln) to the encoded protein. This causes increased level of a brain protein that causes apoptosis. Large Scale Mutations Insertion: ranges from one to thousands extra nucleotides into the DNA. These mutations are also called indels, for insertion/deletion. They are usually errors during replication of repeating elements (e.g. AT repeats). 1 5 Induced mutations These mutations at the molecular level can be caused by specific but sometimes simple chemical substances Chemically induced mutations by Nitrosoguanidine (NTG) Base analogs (e.g. BrdU) Simple chemicals (e.g. acids) Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) Methylating agents (e.g. ethane methyl sulfonate (EMS)) DNA intercalating agents (e.g. ethidium bromide) DNA crosslinker (e.g. platinum) Oxygen radicals Mutations 1 5 Polycyclic hydrocarbons (e.g. benzopyrenes found in internal combustion engine exhaust and charbroiled food) Benzo(a)pyrene Radiation Induced Mutations Mutations can be caused by electromagnetic radiation: Ultraviolet radiation High energy ionizing radiation, such as from X-rays, and radioactive decay. Mutations 1 5 Bioinorganic Chemistry CHEM-332 Genetic Mutations