What is the difference between a missense mutation and a silent mutation

But sometimes they make no difference at all, or very little difference. Sometimes missense mutations cause amino acids to be incorporated, which make the protein more effective in doing its job. More frequently, it causes the protein to be less effective in doing its job. But this is really the grist of evolution, when missense mutations happen, and therefore small changes, frequently small changes in proteins, happen, and it happens to be that it improves the function of a protein.

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. However, frameshift mutations , caused by insertions or deletions of a number of nucleotides that are not a multiple of three are extremely problematic because a shift in the reading frame results Figure 1.

Because ribosomes read the mRNA in triplet codons, frameshift mutations can change every amino acid after the point of the mutation. The new reading frame may also include a stop codon before the end of the coding sequence. Consequently, proteins made from genes containing frameshift mutations are nearly always nonfunctional. Figure 1.

Click for a larger image. Mutations can lead to changes in the protein sequence encoded by the DNA. Since the first case of infection with human immunodeficiency virus HIV was reported in , nearly 40 million people have died from HIV infection, [1] the virus that causes acquired immune deficiency syndrome AIDS.

There is no cure for HIV infection, but many drugs have been developed to slow or block the progression of the virus. Unfortunately, this is also a part of the world where prevention strategies and drugs to treat the infection are the most lacking. Figure 2. HIV is highly prevalent in sub-Saharan Africa, but its prevalence is quite low in some other parts of the world. In recent years, scientific interest has been piqued by the discovery of a few individuals from northern Europe who are resistant to HIV infection.

In , American geneticist Stephen J. CCR5 is a coreceptor found on the surface of T cells that is necessary for many strains of the virus to enter the host cell. The mutation leads to the production of a receptor to which HIV cannot effectively bind and thus blocks viral entry.

People homozygous for this mutation have greatly reduced susceptibility to HIV infection, and those who are heterozygous have some protection from infection as well. It is not clear why people of northern European descent, specifically, carry this mutation, but its prevalence seems to be highest in northern Europe and steadily decreases in populations as one moves south.

Research indicates that the mutation has been present since before HIV appeared and may have been selected for in European populations as a result of exposure to the plague or smallpox.

This mutation may protect individuals from plague caused by the bacterium Yersinia pestis and smallpox caused by the variola virus because this receptor may also be involved in these diseases. 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.