A frameshift mutation affects the grouping of these bases and hence the amino acid coding. Typically, the resultant protein is nonfunctional. Frameshift mutations can occur as a result of insertions, deletions, or duplications. They can also arise from mutations in genes that control DNA replication or repair. Examples include BRCA1 and BRCA2.
Frameshift mutations can be classified into three groups: (i) insertion-deletion (indel), (ii) one-base pair deletion, and (iii) one-base pair insertion.
An indel frame shift mutation occurs when a sequence insertion or deletion causes a reading frame shift. These mutations typically involve small sequences of 1-20 bases. They can be caused by random events during DNA replication or transcription, but may also be associated with genetic instability (see below). For example, an indel mutation may cause a gene to produce an abnormal protein because it contains a sequence not found in the normal gene. This type of mutation may also explain why some people who inherit two copies of a defective gene experience disease while others who inherit the same genes do not.
A one-base pair deletion frame shift mutation occurs when a single base is deleted from a codon. The resulting amino acid change may or may not affect the function of the protein.
A reading frame is made up of groups of three bases, each of which codes for one amino acid. Insertions and deletions change the sequence of DNA in such a way that creates a gap where there should be a base pair. This usually causes a shift in the reading frame and a termination signal to end protein production. However, an insertion or deletion may not cause a termination signal if it falls within a region known as a splice site. Splice sites are nucleotide sequences at the beginning and end of an intron that are recognized and used by the cell to remove the intron from the mRNA template and join the remaining exons together again to make a functional protein.
Deletions involve the removal of bases within the genome of an organism. This can happen as a result of radiation or chemicals damage to the DNA. If the missing section of DNA contains information for making a gene product, then this product will be deleted from the cell. Otherwise, the cell will try to repair the damage using information from homologous genes or else stop dividing and enter dormancy until the stress has been fixed.
Insertions include changing the order of bases in the genome of an organism.
Frameshift mutations are insertions or deletions in the genome that are not three nucleotide multiples. Substitutions in which one nucleotide substitutes another are not considered frameshift mutations. The polypeptide changes by a single amino acid in replacement mutations. In deletion mutations, there is no protein sequence because of the absence of some of the coding DNA. In insertion mutations, part of the gene is inserted into the mRNA from an adjacent gene (or genes). This can have important effects on the resulting protein if the inserted sequence codes for a new domain of life or alters the reading frame such that it starts producing a different protein.
A substitution frameshift occurs when one base in DNA is replaced with another. This can be any pair of bases, but they usually are A-T or G-C. When this happens, the cell replaces that base with a similar looking base. So instead of having a cytosine at that spot, you have a thymine. Instead of having a guanine at that spot, you have an adenine. This is called a substitution frameshift because one nucleotide has been substituted for another.
A deletion frameshift occurs when an entire section of DNA is removed from the gene. Because there is no genetic code to translate into proteins, this type of mutation results in a stop codon being read by the ribosome and terminated translation early.
Frameshift mutations affect the polypeptide more dramatically than missense or nonsense mutations. Instead of modifying only one amino acid, frameshifts affect all of the amino acids in the rest of the gene. This is because the cell does not go back to re-use an exon's codons; instead it creates a new sequence of codons at the site of the defect.
Missense mutations modify only one amino acid in the protein, so they have less of an impact than frameshifts. Nonsense mutations cause the translation of an entire codon to be interrupted, resulting in a stop signal being sent to the ribosome and stopping the synthesis of the protein completely.
The most severe effect of a frameshift mutation is when it occurs in an essential gene. An essential gene is one that is needed for life to exist. Because of this, any change to these genes will necessarily lead to death of the organism. A frameshift mutation in an essential gene would thus be considered lethal. Other types of mutations may also be lethal depending on the location of the mutation within the gene.
Lethal mutations are always negative effects on the protein.
A frameshift mutation is a kind of mutation that involves the insertion or deletion of a nucleotide with an odd number of deleted base pairs. If this reading frame is disrupted by a mutation, the whole DNA sequence after the mutation will be read erroneously. This type of mutation can cause many genetic diseases.
The name "frameshift" comes from the fact that the mutant gene product is likely to be prematurely terminated because it lacks the normal complement of amino acids in its sequence. Thus, a frameshift mutation produces an altered protein with only part of its sequence containing amino acids.
For example, if a patient has a mutation in which a single cytosine is inserted into DNA between two adenosines (a cytosine-adenine-cytosine sequence instead of the usual cytosine-guanine-cytosine sequence), the reading frame of the gene is disrupted. The codon for arginine is interrupted by the premature termination signal, so translation of the RNA transcript yields a shortened protein lacking all but six amino acids of its sequence.
This form of mutation can lead to disease if the truncated protein is not produced at sufficient levels. In such cases, transcription of alternative splice variants may overcome this problem.
Point mutations occur when one base pair is replaced by another, whereas frameshift mutations occur when base pairs are inserted or deleted from the DNA structure. This can have a significant effect on the reading frame of the gene, which in turn can cause a mutation in the encoded protein.
Frameshift mutations can be caused by either insertion elements or deletion elements. Insertion elements do so by inserting themselves into the genome and reproducing until they find a cellular nucleus that will allow them to integrate their DNA into its genome. Deletion elements do so by deleting pieces of DNA containing genes that it needs to survive. Humans have evolved mechanisms to prevent insertion elements from invading our genome, but those same mechanisms may not work for deletion elements because these elements contain genes that are detrimental to their host cell.
Deletion elements can also cause frameshift mutations by removing bases from the sequence of the DNA. These bases are called splice sites, and they help the DNA-making process by indicating where the gene should be cut out and then put back together. If a deletion element removes all of the splice sites, then there will be no indication as to where the gene should be split up and then put back together, and thus it will produce faulty proteins.