Deoxyribonucleic acid, or DNA, is the fundamental instruction manual for all living organisms. It carries the genetic information that directs development, functioning, growth, and reproduction. Often described as the blueprint for life, DNA stores and transmits the genetic information defining our traits. Changes in this blueprint, known as genetic mutations, can alter these instructions and impact an organism’s health.
How Genes Are Read
The genetic information within DNA is organized into segments called genes, which contain the instructions for building proteins. To create a protein, the DNA sequence is first copied into a messenger molecule called RNA. This RNA sequence is then “read” in specific units called codons. Each codon consists of three consecutive nucleotides, acting like a three-letter word in the genetic code.
These codons specify which amino acid should be added to a growing protein chain. Their sequence is read sequentially and without overlap, establishing a “reading frame.” This frame is set by a specific “start codon” (typically AUG) and continues in triplets, ensuring the correct amino acid sequence is produced. Maintaining this reading frame is essential for the cell to accurately translate the genetic message into the intended protein.
What Causes a Frameshift
A frameshift mutation is a genetic change that significantly alters how the genetic code is read. This mutation occurs when nucleotides are inserted or deleted within a DNA sequence, and the number is not a multiple of three. For example, adding or removing one, two, four, or five nucleotides causes a frameshift.
When such an insertion or deletion happens, it shifts the entire reading frame downstream from the mutation point. Imagine reading a sentence where each word has three letters; if one letter is unexpectedly added or removed, all subsequent words become scrambled. Similarly, the cell’s machinery misinterprets every codon after the frameshift, assembling a completely different sequence of amino acids from that point onward.
The frameshift’s location plays a role in its severity. If the insertion or deletion occurs early in the gene, a larger portion of the resulting protein will be miscoded. Frameshift mutations are distinct from substitutions, where one nucleotide is replaced by another, as substitutions typically affect only a single codon or amino acid.
Impact on Proteins
The alteration of the reading frame due to a frameshift mutation significantly impacts the protein produced. All subsequent codons after the mutation are misread, causing the cell to incorporate incorrect amino acids into the protein chain. This results in a completely different amino acid sequence from what was intended.
Often, this altered reading frame prematurely encounters a “stop codon.” Stop codons are specific three-nucleotide sequences that signal protein synthesis termination. When a frameshift mutation creates an early stop codon, protein synthesis ends abruptly, resulting in a shortened, or “truncated,” protein. These truncated proteins are typically non-functional or severely impaired, as they lack essential structural parts for proper operation.
If a premature stop codon is not immediately encountered, the frameshift still leads to an entirely new amino acid sequence, producing a protein with a different structure. Regardless of truncation, the altered protein will likely be non-functional or have significantly altered function, because its three-dimensional shape and active sites are disrupted.
Why Frameshifts Matter
Frameshift mutations often lead to non-functional proteins, which has significant biological implications. Proteins perform nearly all cellular functions, acting as enzymes, structural components, and signaling molecules. When an essential protein is non-functional, it can severely disrupt normal cellular activities.
These mutations are associated with various genetic disorders and diseases. For instance, frameshift mutations cause conditions such as cystic fibrosis, Tay-Sachs disease, and certain cancers. Their impact varies depending on the specific gene affected and mutation location. Understanding frameshift mutations helps explain the molecular basis of many inherited conditions.