What is the difference between silent and missense mutation

Carbon Cycling 4. Climate Change 5: Evolution 1. Evolution Evidence 2. Natural Selection 3. Classification 4. Cladistics 6: Human Physiology 1. Digestion 2. The Blood System 3.

Disease Defences 4. Gas Exchange 5. Homeostasis Higher Level 7: Nucleic Acids 1. DNA Structure 2. Transcription 3. Translation 8: Metabolism 1. Metabolism 2. Cell Respiration 3. Photosynthesis 9: Plant Biology 1. Xylem Transport 2. Phloem Transport 3. Plant Growth 4. Plant Reproduction Genetics 1. Meiosis 2. Inheritance 3.

Speciation Animal Physiology 1. Antibody Production 2. Movement 3. The Kidney 4. The age of this mutation is a matter of debate, but estimates suggest it appeared between years to years ago, and may have been spread from Northern Europe through Viking invasions.

Although DNA testing to determine which individuals carry the CCR5-delta 32 mutation is possible, there are documented cases of individuals homozygous for the mutation contracting HIV.

For this reason, DNA testing for the mutation is not widely recommended by public health officials so as not to encourage risky behavior in those who carry the mutation. Mistakes in the process of DNA replication can cause spontaneous mutations to occur. The error rate of DNA polymerase is one incorrect base per billion base pairs replicated.

Exposure to mutagens can cause induced mutations , which are various types of chemical agents or radiation Table 1. Exposure to a mutagen can increase the rate of mutation more than fold.

Mutagens are often also carcinogens , agents that cause cancer. However, whereas nearly all carcinogens are mutagenic, not all mutagens are necessarily carcinogens. Various types of chemical mutagens interact directly with DNA either by acting as nucleoside analogs or by modifying nucleotide bases. Chemicals called nucleoside analogs are structurally similar to normal nucleotide bases and can be incorporated into DNA during replication Figure 3.

These base analogs induce mutations because they often have different base-pairing rules than the bases they replace.

Other chemical mutagens can modify normal DNA bases, resulting in different base-pairing rules. For example, nitrous acid deaminates cytosine, converting it to uracil. Uracil then pairs with adenine in a subsequent round of replication, resulting in the conversion of a GC base pair to an AT base pair. Nitrous acid also deaminates adenine to hypoxanthine, which base pairs with cytosine instead of thymine, resulting in the conversion of a TA base pair to a CG base pair.

Figure 3. This chemical modification, as shown here, results in converting a CG base pair to a TA base pair. Chemical mutagens known as intercalating agents work differently.

These molecules slide between the stacked nitrogenous bases of the DNA double helix, distorting the molecule and creating atypical spacing between nucleotide base pairs Figure 4. As a result, during DNA replication, DNA polymerase may either skip replicating several nucleotides creating a deletion or insert extra nucleotides creating an insertion.

Either outcome may lead to a frameshift mutation. Combustion products like polycyclic aromatic hydrocarbons are particularly dangerous intercalating agents that can lead to mutation-caused cancers.

The intercalating agents ethidium bromide and acridine orange are commonly used in the laboratory to stain DNA for visualization and are potential mutagens. Figure 4. Intercalating agents, such as acridine, introduce atypical spacing between base pairs, resulting in DNA polymerase introducing either a deletion or an insertion, leading to a potential frameshift mutation.

Exposure to either ionizing or nonionizing radiation can each induce mutations in DNA, although by different mechanisms. Strong ionizing radiation like X-rays and gamma rays can cause single- and double-stranded breaks in the DNA backbone through the formation of hydroxyl radicals on radiation exposure Figure 5. Ionizing radiation can also modify bases; for example, the deamination of cytosine to uracil, analogous to the action of nitrous acid.

Nonionizing radiation, like ultraviolet light, is not energetic enough to initiate these types of chemical changes. However, nonionizing radiation can induce dimer formation between two adjacent pyrimidine bases, commonly two thymines, within a nucleotide strand.

During thymine dimer formation, the two adjacent thymines become covalently linked and, if left unrepaired, both DNA replication and transcription are stalled at this point. DNA polymerase may proceed and replicate the dimer incorrectly, potentially leading to frameshift or point mutations. Figure 5. The process of DNA replication is highly accurate, but mistakes can occur spontaneously or be induced by mutagens.

Uncorrected mistakes can lead to serious consequences for the phenotype. Cells have developed several repair mechanisms to minimize the number of mutations that persist.

Most of the mistakes introduced during DNA replication are promptly corrected by most DNA polymerases through a function called proofreading. In proofreading , the DNA polymerase reads the newly added base, ensuring that it is complementary to the corresponding base in the template strand before adding the next one. If an incorrect base has been added, the enzyme makes a cut to release the wrong nucleotide and a new base is added. Some errors introduced during replication are corrected shortly after the replication machinery has moved.

This mechanism is called mismatch repair. The enzymes involved in this mechanism recognize the incorrectly added nucleotide, excise it, and replace it with the correct base. One example is the methyl-directed mismatch repair in E. The DNA is hemimethylated. This means that the parental strand is methylated while the newly synthesized daughter strand is not.

It takes several minutes before the new strand is methylated. MutH cuts the nonmethylated strand the new strand. An exonuclease removes a portion of the strand including the incorrect nucleotide. Because the production of thymine dimers is common many organisms cannot avoid ultraviolet light , mechanisms have evolved to repair these lesions. In nucleotide excision repair also called dark repair , enzymes remove the pyrimidine dimer and replace it with the correct nucleotides Figure 6.

If a distortion in the double helix is found that was introduced by the pyrimidine dimer, the enzyme complex cuts the sugar-phosphate backbone several bases upstream and downstream of the dimer, and the segment of DNA between these two cuts is then enzymatically removed. DNA pol I replaces the missing nucleotides with the correct ones and DNA ligase seals the gap in the sugar-phosphate backbone.

The direct repair also called light repair of thymine dimers occurs through the process of photoreactivation in the presence of visible light. An enzyme called photolyase recognizes the distortion in the DNA helix caused by the thymine dimer and binds to the dimer. Then, in the presence of visible light, the photolyase enzyme changes conformation and breaks apart the thymine dimer, allowing the thymines to again correctly base pair with the adenines on the complementary strand.

Photoreactivation appears to be present in all organisms, with the exception of placental mammals, including humans. Photoreactivation is particularly important for organisms chronically exposed to ultraviolet radiation , like plants, photosynthetic bacteria, algae, and corals, to prevent the accumulation of mutations caused by thymine dimer formation. Figure 6. Bacteria have two mechanisms for repairing thymine dimers.

One common technique used to identify bacterial mutants is called replica plating. This technique is used to detect nutritional mutants, called auxotrophs , which have a mutation in a gene encoding an enzyme in the biosynthesis pathway of a specific nutrient, such as an amino acid.

As a result, whereas wild-type cells retain the ability to grow normally on a medium lacking the specific nutrient, auxotrophs are unable to grow on such a medium. During replica plating Figure 7 , a population of bacterial cells is mutagenized and then plated as individual cells on a complex nutritionally complete plate and allowed to grow into colonies.

Cells from these colonies are removed from this master plate, often using sterile velvet. This velvet, containing cells, is then pressed in the same orientation onto plates of various media.

At least one plate should also be nutritionally complete to ensure that cells are being properly transferred between the plates. The other plates lack specific nutrients, allowing the researcher to discover various auxotrophic mutants unable to produce specific nutrients.

Cells from the corresponding colony on the nutritionally complete plate can be used to recover the mutant for further study. Figure 7. Identification of auxotrophic mutants, like histidine auxotrophs, is done using replica plating. After mutagenesis, colonies that grow on nutritionally complete medium but not on medium lacking histidine are identified as histidine auxotrophs.

The Ames test , developed by Bruce Ames — in the s, is a method that uses bacteria for rapid, inexpensive screening of the carcinogenic potential of new chemical compounds. The test measures the mutation rate associated with exposure to the compound, which, if elevated, may indicate that exposure to this compound is associated with greater cancer risk.

The Ames test uses as the test organism a strain of Salmonella typhimurium that is a histidine auxotroph, unable to synthesize its own histidine because of a mutation in an essential gene required for its synthesis. After exposure to a potential mutagen, these bacteria are plated onto a medium lacking histidine, and the number of mutants regaining the ability to synthesize histidine is recorded and compared with the number of such mutants that arise in the absence of the potential mutagen Figure 8.

Chemicals that are more mutagenic will bring about more mutants with restored histidine synthesis in the Ames test. Because many chemicals are not directly mutagenic but are metabolized to mutagenic forms by liver enzymes, rat liver extract is commonly included at the start of this experiment to mimic liver metabolism.

After the Ames test is conducted, compounds identified as mutagenic are further tested for their potential carcinogenic properties by using other models, including animal models like mice and rats. Figure 8. The Ames test is used to identify mutagenic, potentially carcinogenic chemicals.

The number of reversion mutants capable of growing in the absence of supplied histidine is counted and compared with the number of natural reversion mutants that arise in the absence of the potential mutagen. Which of the following is the type of DNA repair in which thymine dimers are directly broken down by the enzyme photolyase? Why is it more likely that insertions or deletions will be more detrimental to a cell than point mutations? Why do you think the Ames test is preferable to the use of animal models to screen chemical compounds for mutagenicity?

Envision that each is a section of a DNA molecule that has separated in preparation for transcription, so you are only seeing the template strand. What type of mutation is each? Skip to main content. Mechanisms of Microbial Genetics. Search for:. Mutations Learning Objectives Compare point mutations and frameshift mutations Describe the differences between missense, nonsense, and silent mutations Describe the differences between light and dark repair Explain how different mutagens act Explain why the Ames test can be used to detect carcinogens Analyze sequences of DNA and identify examples of types of mutations.

Think about It What type of a mutation occurs when a gene has two fewer nucleotides in its sequence? Think about It What are the reasons a nucleotide change in a gene for a protein might not have any effect on the phenotype of that gene?