A deleterious mutation is a change in an organism’s DNA that diminishes its fitness, negatively impacting its ability to survive and reproduce. This genetic alteration can increase susceptibility to a disease or disorder. While it may make symptoms more likely, it does not always guarantee their onset. This type of genetic change is also called a disease-causing mutation or a pathogenic variant.
Mechanisms of Genetic Harm
Genetic information begins with DNA, which contains instructions for life. These instructions are copied into messenger RNA (mRNA) through transcription. The mRNA then serves as a template for building proteins, which carry out most biological functions. This flow of information from DNA to RNA to protein is called the central dogma of molecular biology.
A deleterious mutation disrupts this process, often by altering the protein produced. A point mutation, for instance, involves a change in just one DNA building block, or nucleotide, within a gene. This single change can lead to a different amino acid being incorporated into the protein, potentially altering its shape and function. Imagine a recipe where a single ingredient is swapped, potentially changing the entire dish.
A more severe disruption can occur with frameshift mutations, which involve the insertion or deletion of nucleotides not in multiples of three. Since protein-building machinery reads DNA instructions in groups of three (codons), adding or removing one or two nucleotides shifts the entire “reading frame.” This results in a completely altered sequence of amino acids from that point onward, often leading to a non-functional or shortened protein. The resulting protein may be improperly folded, absent entirely, or unable to perform its specific role.
Spectrum of Effects and Examples
The consequences of deleterious mutations exist on a wide spectrum, ranging from mildly detrimental effects that slightly reduce an organism’s fitness to severe, lethal conditions. The impact depends on the specific gene affected, the type of mutation, and the protein’s importance to cellular function.
Cystic Fibrosis, for example, is a genetic disorder caused by mutations in the CFTR gene. This gene provides instructions for making a protein that regulates the movement of salt and water in and out of cells. Mutations in CFTR lead to a faulty or absent protein, resulting in thick, sticky mucus buildup in the lungs, pancreas, and other organs, impairing their function. Individuals with Cystic Fibrosis experience persistent lung infections, difficulty breathing, and digestive problems.
Huntington’s Disease offers another illustration of a deleterious mutation’s impact, caused by an expansion of a specific DNA segment within the HTT gene. This expansion leads to an abnormally long huntingtin protein, which accumulates and damages nerve cells in the brain. The progressive degeneration of these brain cells results in uncontrolled movements, cognitive decline, and psychiatric problems that worsen over time.
Sickle Cell Anemia is a well-known example resulting from a single point mutation in the gene for beta-globin, a component of hemoglobin in red blood cells. This mutation causes red blood cells to become stiff, sticky, and sickle-shaped under certain conditions, instead of their usual round, flexible form. These misshapen cells can block blood flow, leading to pain, organ damage, and a reduced lifespan for red blood cells, causing anemia.
Inheritance and Population Dynamics
Deleterious mutations can arise as somatic mutations or germline mutations. Somatic mutations occur in body cells after conception and are not passed down to offspring; for example, a mutation in a skin cell caused by sun exposure. In contrast, germline mutations occur in reproductive cells (sperm or egg) and can be inherited by future generations.
When a germline mutation is passed on, its expression in offspring depends on inheritance patterns. In dominant inheritance, only one copy of the mutated gene is needed for the condition to manifest, as seen in Huntington’s Disease. If one parent has the dominant mutation, there is a 50% chance their child will inherit it and develop the condition. With recessive inheritance, like in Cystic Fibrosis or Sickle Cell Anemia, an individual must inherit two copies of the mutated gene—one from each parent—to express the disorder. Individuals with only one copy of a recessive mutation are carriers and do not show symptoms but can pass the mutation to their children.
Natural selection plays a role in managing the frequency of deleterious mutations within a population. This process, known as purifying selection, gradually removes harmful mutations from the gene pool. Mutations that severely reduce an organism’s fitness are less likely to be passed on because affected individuals may not survive to reproduce or may have fewer offspring. However, recessive mutations can persist at low frequencies in carrier individuals, as they are not directly exposed to selection pressure.
The Environmental Context of Mutations
The impact of a mutation is not always absolute and can be significantly influenced by the surrounding environment. What is considered “deleterious” in one context might be neutral or even beneficial in another. This highlights that a mutation’s effect on fitness is context-dependent, not an inherent property.
A classic illustration of this environmental interplay is the sickle cell trait. As previously mentioned, having two copies of the mutated beta-globin gene causes Sickle Cell Anemia, a severe condition. However, individuals who inherit only one copy of the sickle cell mutation (carriers) do not experience severe symptoms of anemia.
Possessing one copy of the sickle cell allele provides protection against malaria, a parasitic disease prevalent in many tropical and subtropical regions. The altered red blood cells in carriers are less hospitable to the malaria parasite, reducing infection severity. In environments where malaria is widespread, the sickle cell trait, despite its potential for harm in two copies, offers a survival advantage, demonstrating how environmental pressures can shape the selective value of a genetic variation.