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. 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.
Based on the above details, let us attempt to answer a few questions by answering the quiz below. This tutorial looks at the mutation at the gene level and the harm it may bring. Learn about single nucleotide polymorphisms, temperature-sensitive mutations, indels, trinucleotide repeat expansions, and gene duplication Read More. This tutorial is a continuation of the first lesson on chromosomal mutation.
Here, find out the chromosomal aberrations involving the genes. Skip to content Main Navigation Search. Dictionary Articles Tutorials Biology Forum. Table of Contents. Biology definition: A frameshift mutation is a type of gene mutation in which the addition or deletion of one or more nucleotides causes a shift in the reading frame of the codons in the mRNA , which may lead to the alteration in the amino acid sequence at protein translation.
Variant: frame shift mutation. Synonyms: reading frame mutation, reading frame shift, or framing error. Compare: base-pair substitution. More Examples The reading frame of any mRNA is the coding sequence for a given polypeptide and is read continuously from the start codon AUG to one of the three stop codons. Effects of frameshift mutation: Frameshift mutations may be beneficial, deleterious, or lethal. For example, induction of frameshift mutation has been used to make certain bacteria capable of producing nylonase, an enzyme that can degrade nylon.
Some cases of albinism have been attributed to the early termination of any of the enzymes necessary for the production of melanin. Tay Sachs disease is caused by various mutations , including frameshift mutations, in the HEXA gene, a gene on chromosome 15 that codes for the alpha-subunit of the lysosomal enzyme beta-N-acetylhexosaminidase A.
Which of the following are considered to be frameshift mutations? Tautomeric shift. Base analog substitution. Insertion and deletion. Which of the following events could result in a frameshift mutation? Point mutation. Silent mutation. Result in an improper sequence of amino acid Sense codons. Missense codons. Non-sense codons. May result in an early truncation of the translation Sense codons.
A disease caused by a frameshift mutation in the gene Hex-A Cystic fibrosis. Leigh disease. Each group of three bases corresponds to one of 20 different amino acids used to build a protein. If a mutation disrupts this reading frame, then the entire DNA sequence following the mutation will be read incorrectly.
A frameshift mutation is a particular type of mutation that involves either insertion or deletion of extra bases of DNA. Now, what's important here is the number three. Otherwise they are considered - frameshifts. Deletions can account for a substantial proportion of spontaneous mutations. They can occur over several nucleotides, short gene-size distances or include large portions of chromosomes. Deletion mutations encompassing specific chromosomal regions are often associated with progression of tumors.
Like frameshift mutations, the prevalence of deletions is context-sensitive. Deletions are considered " illegitimate " recombination events because they were originally thought to occur at non-homologous sequences. However, sequence analysis of deletion mutations Albertini et al shows that deletion mutations do not occur at random but tend to occur at short repeated sequences bp in length so limited homology may be important even for illegitimate recombination.
Hot spots for deletion are such repeated structures associated with inverted repeat possible hairpin structures. Some deletions occur between much larger repeats: between tandem arrays of duplicated genes e. IS or REP elements in bacteria, retron or retrotransposon elements in eukaryotes. Several prevalent human genetic syndromes fall into this category: male color-blindness, thalessemias. Lovett et al. Most likely, each of these mechanisms can account for a subset of observed deletion mutations.
Like deletions, gene duplications or amplifications can arise at short or long repeated sequences.
0コメント