Heterozygote advantage describes a genetic situation where an individual inheriting two different versions, or alleles, of a gene experiences a survival or reproductive benefit compared to those with two identical versions. This occurs when a single copy of an allele, potentially detrimental in two copies, offers protection under specific environmental conditions.
Genetic Building Blocks
A gene is a segment of DNA that carries instructions for building a specific protein or function. Alleles are different forms of the same gene, each inherited from one parent. An individual’s genotype refers to the specific combination of alleles they possess for a particular gene.
When an individual inherits two identical alleles for a gene, they are homozygous. If they inherit two different alleles, they are heterozygous. The observable traits resulting from a genotype are called the phenotype.
How Heterozygote Advantage Works
Heterozygote advantage involves a delicate balance: one copy of an allele, often associated with disease in two copies, confers an unexpected benefit. This benefit typically arises from an environmental challenge, such as an infectious disease. The single altered allele can subtly change a protein or cellular process, making the individual less susceptible to the environmental threat.
Individuals with two normal gene copies are susceptible to environmental pressure, while those with two altered alleles develop a severe condition. The heterozygous state, with one normal and one altered allele, provides a middle ground. This means the protective effect is present without the full severity of the disease. This genetic balancing act allows the altered allele to persist in populations because the advantage it provides to heterozygotes outweighs the disadvantage to those who inherit two copies.
Prominent Examples
One well-known instance of heterozygote advantage is the sickle cell trait, which protects against malaria. Individuals heterozygous for the hemoglobin S (HbS) allele (HbAS genotype) are resistant to severe malaria caused by Plasmodium falciparum. Their red blood cells are less hospitable to the parasite, reducing its growth and multiplication. Infected HbAS red blood cells may also prematurely sickle and be removed by the spleen, eliminating parasites. This advantage is prevalent in malaria-prone regions like Sub-Saharan Africa, India, the Middle East, and the Mediterranean.
Conversely, individuals homozygous for the normal HbA allele are susceptible to severe malaria, while those homozygous for the HbS allele develop sickle cell disease, a serious blood disorder. The sickle cell trait’s protective effect against malaria has led to the HbS allele’s persistence in malaria-endemic areas.
Another example of heterozygote advantage involves carriers of the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation, who may have increased resistance to certain infectious diseases. The CFTR gene produces a protein that transports chloride and bicarbonate ions across cell membranes. Individuals with two mutated CFTR gene copies develop cystic fibrosis, a severe condition affecting multiple organs.
However, carrying one mutated CFTR allele (heterozygous) offers some protection against cholera. Cholera toxin normally activates the CFTR protein, causing excessive fluid loss and severe diarrhea. Heterozygous individuals produce about half the normal functional CFTR protein, reducing fluid secretion and lessening dehydration severity.
Additionally, heterozygous CFTR carriers may have some resistance to typhoid fever. Salmonella typhi, which causes typhoid, uses normal CFTR protein to enter intestinal cells. In carriers with reduced functional CFTR, fewer bacteria may invade, potentially conferring protection. While exact mechanisms and protection extent are still being explored, these examples illustrate how specific genetic variations can provide an unexpected survival benefit.