Indels, short for insertions and deletions, are a type of genetic variation involving the addition or removal of nucleotides within a DNA sequence. These changes differ from other genetic alterations, such as point mutations, where a single nucleotide is replaced without changing the total number of bases. Indels are fundamental in shaping the genetic makeup of organisms and influence various biological traits.
Understanding Insertions and Deletions
Indels vary considerably in size, from a single nucleotide to thousands of nucleotides. Small indels typically involve fewer than 50 nucleotides, frequently occurring in gene coding regions and potentially disrupting their function. Larger indels, involving thousands of nucleotides, often affect gene regulation, gene expression, and the overall structure of the genome. Indels are a common form of genetic variation, making up between 16% and 25% of all sequence polymorphisms in humans.
How Indels Arise
Indels originate through several biological mechanisms, primarily errors during DNA replication, DNA repair processes, and recombination. During DNA replication, a common cause is DNA polymerase slippage, particularly in regions with repetitive sequences like homopolymers or microsatellites. This slippage can lead to misalignments between the template strand and the newly synthesized strand, resulting in an insertion or deletion.
Errors can also occur during the repair of DNA double-strand breaks. One repair pathway, non-homologous end joining (NHEJ), can inaccurately repair broken DNA, leading to the random removal or addition of nucleotides. Recombination errors, such as unequal crossing over during meiosis, can result in one chromatid gaining an insertion while the homologous chromatid experiences a deletion.
The Molecular Consequences of Indels
The impact of indels on the genetic code and protein synthesis depends heavily on their size and location within a gene. If an indel is not a multiple of three nucleotides, it causes a frameshift mutation. This shifts the DNA sequence’s reading frame, altering every downstream codon and typically leading to the production of a non-functional protein that is often abnormally short or long.
Indels that are a multiple of three nucleotides (e.g., 3, 6, or 9 nucleotides) are non-frameshift mutations. These in-frame indels result in the insertion or deletion of entire amino acids within the protein sequence, without disrupting the reading frame. While such changes can affect protein function, they do not necessarily lead to a complete loss of function. Indels can also affect gene regulation by occurring in non-coding regions like promoter or enhancer sequences, influencing how genes are expressed.
Indels in Health and Evolution
Indels contribute significantly to human genetic diversity and are implicated in various genetic diseases. For instance, cystic fibrosis is often caused by a three-base pair deletion in the CFTR gene, leading to a non-functional protein unable to regulate chloride transport. Huntington’s disease arises from an expansion of a trinucleotide repeat (an insertion) in the HTT gene, leading to an abnormal protein that accumulates in the brain. Duchenne muscular dystrophy can also be caused by indels, often leading to frameshift mutations in the dystrophin gene.
Beyond disease, indels are a driving force in evolution, contributing to adaptation and diversification across species. They can introduce new genetic variation, allowing populations to adapt to changing environmental conditions. Indels can also alter gene function or create new genes, influencing evolutionary trajectories. By modifying regulatory regions, indels can change gene expression patterns, impacting an organism’s ability to respond to its environment and shaping genome structure.