Point mutations usually occur during DNA replication. DNA replication occurs when a double-stranded DNA molecule creates two single strands of DNA, each of which is a model for creating the complementary strand. A single point mutation can alter the entire DNA sequence. Changing a purine or pyrimidine can change the amino acid for which nucleotides code. These sample phrases are automatically selected from various online information sources to reflect the current use of the word «point mutation». The views expressed in the examples do not represent the views of Merriam-Webster or its editors. Send us your feedback. A point mutation occurs in a genome when a single base pair is added, removed, or modified. Although most point mutations are benign, they can also have various functional consequences, including changes in gene expression or changes in encoded proteins. A substitution mutation occurs when one base pair is replaced by another. This would be the case, for example, if a nucleotide containing cytosine was accidentally replaced by a nucleotide containing guanine. There are three types of surrogate mutations: A point mutation is defined as a change in a single pair of nucleotides in the DNA molecule and usually results in a change in a single biochemical function. Missense mutations code for another amino acid.
A missense mutation changes one codon to create another protein, a non-synonymous change. [4] Preservative mutations lead to an amino acid change. However, the properties of the amino acid remain the same (e.g. hydrophobic, hydrophilic, etc.). Sometimes a change in an amino acid in the protein is not harmful to the body as a whole. Most proteins can resist one or two point mutations before their function changes. Non-conservative mutations result in a change in amino acid that has different characteristics than the wild type. The protein can lose its function, which can lead to disease in the body. For example, sickle cell disease is caused by a point mutation (a missense mutation) in the beta-hemoglobin gene, which converts a GAG codon into GUG, which codes for the amino acid valine rather than glutamic acid. The protein can also have a «functional gain» or be activated, as is the case with the mutation that modifies a valine to glutamic acid in the BRAF gene; This leads to activation of the RAF protein, which causes unlimited proliferative signaling in cancer cells. [5] These are two examples of a non-conservative mutation (missense).
There are several ways in which point mutations can occur. First, ultraviolet (UV) light and high-frequency light are able to ionize electrons, which can affect DNA. Oxygen molecules reactive with free radicals, which are a byproduct of cellular metabolism, can also be very harmful to DNA. These reagents can lead to both single-stranded DNA breaks and double-stranded DNA breaks. Third, the bonds in DNA eventually break, creating another problem of maintaining DNA integrity at a high level. There may also be replication errors that result in substitution, insertion, or delete mutations. By changing a single amino acid, the entire peptide can change, altering the entire protein. The new protein is called the protein variant. If the original protein functions in cell reproduction, this single point mutation can alter the entire cellular reproduction process of that organism. Silent mutations code for the same amino acid (a «synonymous substitution»).
A silent mutation has no effect on the function of the protein. A single nucleotide can change, but the new codon specifies the same amino acid, resulting in an unmutated protein. This type of modification is called a synonymous change because the old and new codon codes for the same amino acid. This is possible because 64 codons specify only 20 amino acids. However, different codons can lead to different levels of protein expression. [4] Like a nonsense mutation, a missense mutation occurs when one nucleotide is substituted and another codon is formed; But this time, the codon that forms is not a stop-codon. Instead, the codon produces another amino acid in the amino acid sequence. For example, if a missense substitution changes a codon from AAG to AGG, the amino acid arginine is produced instead of lysine.
A missense mutation is considered conservative if the amino acid formed by the mutation has properties similar to what should be formed instead. It is said to be not preservative if the amino acid has different properties that have the structure and function of a protein. People with color blindness have mutations in their genes that cause the loss of red or green cones, and so they have trouble distinguishing colors. There are three types of cones in the human eye: red, green, and blue. Now, researchers have discovered that some people with the genetic mutation that causes color blindness lose a whole bunch of «color cones» without altering the clarity of their overall vision. [20] Point mutations that occur in non-coding sequences generally have no consequences, although there are exceptions. If the mutant base pair is in the promoter sequence of a gene, the expression of the gene may change. If the mutation occurs in the splicing site of an intron, it can interfere with the correct splicing of the transcribed pre-mRNA. DNA and RNA have a double helix structure. Phosphate groups and 5-carbon sugars form the backbone, while the center of the double helix is formed by nitrogenous base pairs.
Each type of nitrogenous base pairs with a different specific base. Cytosine associates with guanine while adenine associates with thymine in DNA and uracil in RNA and vice versa. For DNA to form proteins, it must be transcribed by messenger RNA (mRNA). The mRNA «reads» the DNA three bases simultaneously and adapts its complementary bases to it. These groups of three bases are called codons, and each codon codes for a different amino acid. Amino acid chains form proteins. Therefore, it is crucial that DNA has the correct sequence of base pairs to make proteins properly. A point mutation may have no effect, or it may alter the protein produced and render it unusable. Point mutations in several tumor suppressor proteins cause cancer.
For example, point mutations in colonic adenomatous polyposis promote tumorigenesis. [9] A new test, rapid parallel proteolysis (FASTpp), could help rapidly investigate specific stability defects in individual cancer patients. [10] Some scientists recognize a different type of mutation, called frameshift mutation, as a point mutation type. Frame shift mutations can lead to a drastic loss of function and occur due to the addition or deletion of one or more DNA bases. In a gene encoding a protein, the sequence of codons that begins with AUG (where U is the base of the uracil RNA that replaces T during transcription) and ends with a termination codon is called a reading frame. When a pair of nucleotides is added or subtracted from this sequence, the reading frame is shifted by one pair of nucleotides from this point, and all downstream codons are modified. The result will be a protein whose first section (before the mutation site) is that of the wild-type amino acid sequence, followed by a tail of functionally meaningless amino acids. Other effects of point mutations or single nucleotide polymorphisms in DNA depend on the location of the mutation in the gene. For example, if the mutation occurs in the region of the gene responsible for encoding, the amino acid sequence of the encoded protein may be altered, resulting in a change in the function, location of the protein, and stability of the protein or protein complex. Many methods have been proposed to predict the effects of missense mutations on proteins. Machine learning algorithms train their models to distinguish known mutations associated with a disease from neutral mutations, while other methods do not explicitly train their models, but almost all methods use evolutionary preservation by assuming that changes in conserved positions tend to be more harmful.