Point Mutation Definition
A point mutation is a type of mutation in DNA or RNA, the cell’s genetic material, in which one single nucleotide base is added, deleted, or changed. DNA and RNA are made up of many nucleotides. There are five different molecules that can make up nitrogenous bases on nucleotides: cytosine, guanine, adenine, thymine (in DNA), and uracil (in RNA), abbreviated C, G, A, T, and U.
The specific sequence of nucleotides encodes all the information for carrying out all cell processes. In general, a mutation is when a gene is altered through a change in DNA structure; this may refer even to entire sections of chromosomes. A point mutation is specifically when only one nucleotide base is changed in some way, although multiple point mutations can occur in one strand of DNA or RNA.
From DNA to Protein
DNA and RNA have a double helix structure. Phosphate groups and 5-carbon sugars make up the backbone, while the middle of the double helix is formed by pairs of nitrogenous bases. Each type of nitrogenous base pairs with another specific base. Cytosine pairs with guanine, while adenine pairs with thymine in DNA and uracil in RNA, and vice versa.
In order for DNA to make proteins, it must be transcribed by messenger RNA (mRNA). The mRNA “reads” the DNA three bases at a time, matching its complementary bases to it. These groups of three bases are called codons, and each codon codes for a different amino acid. Chains of amino acids make up proteins. Therefore, it is vitally important that the DNA has the correct sequence of base pairs in order to make proteins correctly. A single point mutation could have no effect, or it could alter the protein that is produced and render it useless.
Point mutations are sometimes caused by mutations that spontaneously occur during DNA replication. The rate of mutations may also increase when a cell is exposed to mutagens, which are environmental factors that can change an organism’s DNA. Some mutagens are X-rays, UV rays, extreme heat, or certain chemicals like benzene.
Types of Point Mutations
A substitution mutation occurs when one base pair is substituted for another. For example, this would occur when one nucleotide containing cytosine is accidentally substituted for one containing guanine. There are three types of substitution mutations:
A nonsense mutation occurs when one nucleotide is substituted and this leads to the formation of a stop codon instead of a codon that codes for an amino acid. A stop codon a certain sequence of bases (TAG, TAA, or TGA in DNA, and UAG, UAA, or UGA in RNA) that stops the production of the amino acid chain. It is always found at the end of the mRNA sequence when a protein is being produced, but if a substitution causes it to appear in another place, it will prematurely terminate the amino acid sequence and prevent the correct protein from being produced.
Like a nonsense mutation, a missense mutation occurs when one nucleotide is substituted and a different codon is formed; but this time, the codon that forms is not a stop codon. Instead, the codon produces a different amino acid in the sequence of amino acids. For example, if a missense substitution changes a codon from AAG to AGG, the amino acid arginine will be produced instead of lysine. A missense mutation is considered conservative if the amino acid formed via the mutation has similar properties to the one that was supposed to be formed instead. It is called non-conservative if the amino acid has different properties that structure and function of a protein.
In a silent mutation, a nucleotide is substituted but the same amino acid is produced anyway. This can occur because multiple codons can code for the same amino acid. For example, AAG and AAA both code for lysine, so if the G is changed to an A, the same amino acid will form and the protein will not be affected.
Insertion and Deletion
An insertion mutation occurs when an extra base pair is added to a sequence of bases. A deletion mutation is the opposite; it occurs when a base pair is deleted from a sequence. These two types of point mutations are grouped together because both of them can drastically affect the sequence of amino acids produced. With one or two bases added or deleted, all of the three-base codons change. This is called a frameshift mutation.
For example, if a sequence of codons in DNA is normally CCT ATG TTT and an extra A is added between the two cytosine bases, the sequence will instead read CAC TAT GTT T. This completely changes the amino acids that would be produced, which in turn changes the structure and function of the resulting protein and can render it useless. Similarly, if one base was deleted, the sequence would also shift.
Examples of Diseases Caused by Point Mutations
Cystic Fibrosis (CF) is a recessive inherited disorder most common among people of European descent. In the United States, 1 in 3500 newborns are born with cystic fibrosis, and 1 in 30 Caucasian Americans is a carrier. There are many different mutations that can cause CF, but the most common one is a deletion of three nucleotides in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that results in the loss of the amino acid phenylalanine and causes an incorrectly folded protein. (Note that this deletion is not a frameshift mutation because three bases next to each other are deleted, and all the other amino acids in the chain remain the same.) CF is associated with thick, sticky mucus in the lungs and trouble breathing, salty sweat, infertility in certain individuals, and a shortened life expectancy (about 42-50 years in developed countries).
Sickle-cell anemia is a recessive disorder caused by a single substitution in the gene that creates hemoglobin, which carries oxygen in the blood. Normally, glutamic acid is produced in the chain, but the substitution causes valine to be produced at that spot instead. When people have two copies of this mutation, it results in thin sickle-shaped blood cells that sometimes cannot carry oxygen properly.
About 80% of people with sickle-cell disease are in sub-Saharan Africa, where being a carrier for sickle-cell anemia (having only one copy of the gene, not two) actually helps protect against malaria. It is also found in other parts of the world such as India and the Middle East and affects about 1 in 500 African Americans. Symptoms include anemia, obstruction of blood vessels, and chest pain, and it is treated with folic acid, blood transfusions, bone marrow transplants, and certain prescription drugs.
Tay-Sachs disease is another recessive disorder caused by point mutations. Different mutations can cause this disorder, but they are all found on the HEXA gene on chromosome 15. Tay-Sachs causes nerve cells to deteriorate over time, which in turn results in the decline of physical and mental functioning. Both child and adult-onset forms of the disease occur, and children with the disease usually die before the age of four. About 1 in 320,000 newborns in the United States develop Tay-Sachs. It occurs in higher frequencies in Ashkenazi Jews, Cajuns, and French Canadians (about 1 in 3500 in these populations), although the mutations associated with the disease are different in each population. There is currently no treatment or cure.