Which of the Following Mutations Would Be Classified as Indels?

A genetic mutation is a change in an organism’s DNA sequence. These alterations are a source of genetic variation and can result in a wide range of effects. Mutations are classified into types based on the changes they cause to the DNA. This article will focus on a specific class of mutations known as indels.

Understanding Indels: Insertions and Deletions

The term “indel” is a portmanteau of “insertion-deletion” and refers to a mutation where nucleotide bases are either added to or removed from a DNA sequence. An insertion is the addition of one or more base pairs. For instance, if a DNA sequence reads as ATGC, an insertion of a G would change it to ATGGC, increasing the segment’s length.

Conversely, a deletion involves the removal of one or more nucleotide base pairs. Using the same ATGC sequence, a deletion of the G would result in ATC, which shortens the DNA segment. The defining characteristic of an indel mutation is this change in the overall length of the DNA sequence.

These mutations can range in size from a single base pair to thousands and often result from errors during DNA replication or repair. The outcome is always a net gain or loss of genetic material, making this change in length the first clue when classifying a mutation.

Indels vs. Other Genetic Mutations

To identify an indel, it is useful to contrast it with other mutation types, especially point mutations. A point mutation, also known as a substitution, is a change where one base pair is replaced by a different one. For example, a sequence of ATGC might be altered to ATTC, where the guanine (G) base is substituted with a thymine (T).

The primary difference is that a substitution does not change the total number of nucleotides in the DNA sequence. The original length is maintained, whereas an indel alters it by adding or removing bases. Indels account for a substantial portion of all genetic variation, estimated to be between 16% and 25% of all sequence polymorphisms in humans.

Identifying Indel Mutations

Identifying an indel mutation involves a direct comparison between an original and a mutated DNA sequence. The key is to look for a change in the length of the sequence. If the mutated sequence is longer than the original, an insertion has occurred. If it is shorter, a deletion has taken place.

Consider these examples. If the original sequence is AGTTCG and the mutated version is AGTTGCG, the addition of a guanine (G) makes it an insertion. If the mutated sequence becomes AGTCG, the loss of a thymine (T) means it is a deletion. However, if the sequence changes to AGCTCG without altering the length, it is a substitution.

Consequences of Indel Mutations

The effects of indel mutations are pronounced when they occur within the coding regions of genes. Genes are read in three-base “codons” that correspond to specific amino acids, the building blocks of proteins. This sequence of codons is known as the “reading frame.” An indel that is not a multiple of three bases, such as the insertion or deletion of a single nucleotide, will shift this entire reading frame.

This “frameshift mutation” alters every codon downstream from the mutation site. The result is a different sequence of amino acids being produced, which almost always leads to a non-functional protein. The frameshift can also introduce a premature stop codon, halting protein synthesis and leading to a truncated product. Such changes are associated with genetic disorders like Bloom syndrome.

In some cases, an indel involves a multiple of three base pairs, which is known as an “in-frame” indel. An in-frame indel adds or removes one or more complete amino acids but does not shift the reading frame for the rest of the gene. While less disruptive than a frameshift, an in-frame indel can still alter the structure and function of the resulting protein.