1 / 22

Mutations General Genetics

Mutations General Genetics. Dr. Attya Bhatti. The Modern Concept.

jenn
Télécharger la présentation

Mutations General Genetics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. MutationsGeneral Genetics Dr. Attya Bhatti

  2. The Modern Concept • Charles Darwin recognized that variation existed in populations and suggested natural selection as a mechanism for choosing some variants over others resulting in survival of the fittest and gradual changes in populations of organisms. • Without a mechanism for generation of new variation, populations would be selected into a corner where only one variation would survive and new species could never arise. • The Modern Synthesis combines the mechanism of mutation in DNA to generate variation with natural selection of individuals in populations to produce new species.

  3. Mutations • A heritable alterations or change in the genetic material. • Biologists use the term “mutation” when talking about any change in the genetic material. Not all result in a change in phenotype. • Polymorphism

  4. Mutations • Somatic Mutations; occur in somatic cells and only affect the individual in which the mutation arises. can not transmitted to offspring. • Gonadal/ Gamete Mutations; Germ-line mutations alter gametes and passed to the next generation.

  5. Mutations are quantified in two ways: • Mutation rate= probability of a particular type of mutation per unit time (or generation). • Mutation frequency= number of times a particular mutation occurs in a population of cells or individuals.

  6. Mutation Rates • The frequency with which a gene changes from the wild type to a mutant is referred to as themutation rate. • Generally expressed as the number of mutations per biological unit, which may be mutations per cell division, per gamete, or per round of replication. • For example, the mutation rate for achondroplasia (a type of hereditary dwarfism) is about four mutations per 100,000 gametes, usually expressed more simply as 4 x 10-5.

  7. Mutation frequency is defined as the incidence of a specific type of mutation within a group of individual organisms. • For achondroplasia, the mutation frequency in the United States is about 2 X 10-4, which means that about 1 of every 20,000 persons in the U.S. population carries this mutation.

  8. Factors affecting Mutation rate 1. They depend on the frequency with which primary changes take place in DNA. Primary change may arise from spontaneous molecular changes in DNA or it may be induced by chemical or physical agents in the environment. • A second factor influencing the mutation rate is the probability that, when a change takes place, it will be repaired. Most cells possess a number of mechanisms to repair altered DNA; so most alterations are corrected before they are replicated. • If these repair systems are effective, mutation rates will be low; if they are faulty, mutation rates will be elevated. • Some mutations increase the overall rate of mutation at other genes; these mutations usually occur in genes that encode components of the replication machinery or DNA repair enzymes.

  9. 3. A third factor, one that influences our ability to calculate mutation rates, is the probability that a mutation will be recognized and recorded. • When DNA is sequenced, all mutations are potentially detectable. In practice, however, sequencing is expensive; so mutations are usually detected by their phenotypic effects. • Some mutations may appear to arise at a higher rate simply because they are easier to detect.

  10. Causes of Mutations Mutation arises in two ways • Errors in DNA Replication • Mutagens

  11. Causes of Mutations • Spontaneous mutations (natural) and rare: 2-12X 10-6 (per generation / gene) • Induced mutations caused by mutagens. Tautomerism - A base is changed by the repositioning of a hydrogen atom. An example is 5-bromo-deoxyuridine (5BU), which can exist in two tautomeric forms: typically it exists in a keto form (T mimic) that pairs with A, but it can also exist in an enol form (C mimic) that pairs with G. Depurination - Loss of a purine base (A or G). Deamination - Changes a normal base to an atypical base; C → U, (which can be corrected by DNA repair mechanisms), Transition - A purine changes to another purine, or a pyrimidine to a pyrimidine. Transversion - A purine becomes a pyrimidine, or vice versa.

  12. Errors in DNA Replication

  13. Induced mutations on the molecular level can be caused by: • Exposure to X-ray, UV light (Radiations) • Chemical treatment: base analogs 5’-bromouracil (=T or rarely C) • hydroxylating agent (add OH-group to C) • alkylating agent such as EMS (ethylmethane sulfonate) • deaminating agent such as nitrous acid • intercalating agent such as Acridine Orange • Transposons that insert into a gene and disrupt the normal reading frame

  14. Ionizing radiations X-rays and gamma rays damage DNA by dislodging electrons from atoms; these electrons then break phosphodiester bonds and alter the structure of bases. Ionizing radiation causes three types of damage to DNA • Single-strand breaks - mostly sealed by DNA ligase • Double-strand breaks - often lethal because can't be resealed by ligase so degraded by nucleases • Alteration of bases - this type of oxidative damage is usually lethal because forms a replication barrier at that site

  15. Radiation • UV radiation – 260-280 nm is wavelength at which maximum absorption occurs for DNA. • Ultraviolet radiation (non-ionizing radiation) excites electrons to a higher energy level. DNA molecules are good absorbers of ultraviolet light. • Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. • UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer. • DNA has so-called hotspots, where mutations occur up to 100 times more frequently than the normal mutation rate. A hotspot can be at an unusual base, e.g., 5-methylcytosine. Mutation rates also vary across species.

  16. Chemical mutagens • Compounds that increase the frequency of some types of mutations. • They vary in their potency since this term reflects; • Their ability to enter the cell, • Their reactivity with DNA, • Their general toxicity, and • The likelihood that the type of chemical change they introduce into the DNA will be corrected by a repair system

  17. Chemical Mutagens • Nitrosoguanidine (NTG), Hydroxylamine NH2OH • Base analogs (e.g. BrdU) • Simple chemicals (e.g. acids) • Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions. • Methylating agents (e.g. ethyl methanesulfonate (EMS) • Polycyclic hydrocarbons (e.g. benzopyrenes) • DNA intercalating agents (e.g. ethidium bromide) • DNA crosslinker (e.g. platinum) • Oxidative damage caused by oxygen (O) radicals

  18. A major problem with chemically-induced and irradiation-induced mutations, however, is that they are generated essentially at random. In order to identify a mutant phenotype of interest, a laborious screen for mutants needs to be conducted by close examination of the phenotypes following mutagenesis. • Transposonsthat insert into a gene and disrupt the normal reading frame

  19. Ames test • The Ames test is based on the principle that both cancer and mutations result from damage to DNA. • The Ames test uses his- strains of bacteria to test chemicals for their ability to produce his-__his+ mutations. Because mutagenic activity and carcinogenic potential are closely correlated, the Ames test is widely used to screen chemicals for their cancer-causing potential.

More Related