Genetic variation is a fundamental characteristic of life, providing the raw material upon which natural selection acts. Within any given population, multiple versions of a single gene exist, leading to a spectrum of observable traits. Typically, if one version of a gene offers a survival or reproductive benefit, natural selection will drive that version to become the most common, eventually eliminating less advantageous alternatives. However, some specific genetic variations persist over long periods, maintaining a stable presence within the gene pool. This stable maintenance of multiple gene forms represents an important compromise in the evolutionary process.
Defining Balanced Polymorphism
Balanced polymorphism is a genetic phenomenon where two or more distinct forms of a gene, known as alleles, are maintained in a population at relatively constant frequencies over many generations. In this balanced state, natural selection prevents any single allele from becoming fixed (100% frequency) or from being completely eliminated. This stable coexistence ensures that the overall genetic makeup of the population remains diverse for that specific gene.
The gene’s location on a chromosome is called a locus, and the different alleles occupying that locus are what create the polymorphism. The defining feature of a balanced polymorphism is the equilibrium state, where the disadvantage of a harmful allele is counterbalanced by an advantage it confers in a different genetic combination. This balancing act is a form of stabilizing selection, which actively preserves the genetic variation rather than removing it.
The Mechanism of Heterozygote Advantage
The primary mechanism responsible for maintaining a balanced polymorphism is known as heterozygote advantage, sometimes called overdominance. This occurs when individuals who possess two different alleles for a specific gene—the heterozygous genotype—have a higher biological fitness than individuals with two identical alleles—the two homozygous genotypes.
Consider a gene with two alleles, A and a, which combine to form three possible genotypes: AA, Aa, and aa. In a heterozygote advantage scenario, the Aa individual is the “fittest,” meaning they have the greatest reproductive success. For this mechanism to work, both homozygous states (AA and aa) must be disadvantaged compared to the heterozygous state (Aa). Natural selection then favors the heterozygote, preserving both the A and the a alleles in the gene pool.
The selection pressure against the less-fit homozygous individuals is offset by the reproductive success of the heterozygotes, who carry and pass on both alleles to the next generation. Even if the ‘a’ allele causes a severe condition when two copies are present (aa), the superior survival of the Aa heterozygotes ensures that the ‘a’ allele is not completely removed from the population. This continuous advantage for the heterozygote is what creates and sustains the stable frequency of both alleles.
Classic Examples in Human Populations
The most widely recognized example of balanced polymorphism in humans involves the gene for hemoglobin and its relationship with the infectious disease malaria. The gene has a normal allele, hemoglobin A (HbA), and a variant allele, hemoglobin S (HbS), which is responsible for sickle cell disease when two copies are inherited. Individuals who are homozygous for the normal allele (HbAA) produce entirely normal red blood cells but are highly susceptible to severe malaria caused by the parasite Plasmodium falciparum.
Conversely, individuals homozygous for the variant allele (HbSS) suffer from sickle cell disease, a severe condition that significantly reduces life expectancy, especially without modern medical care. The selection pressure against these two groups is intense: malaria eliminates HbAA individuals, and sickle cell disease eliminates HbSS individuals. This leaves the heterozygous individuals (HbAS), who possess one normal and one sickle cell allele, with the highest fitness in environments where malaria is widespread.
The HbAS heterozygotes, who have what is known as sickle cell trait, typically do not experience the severe symptoms of sickle cell disease but possess a marked resistance to the lethal effects of malaria. Their red blood cells are slightly altered, which interferes with the malaria parasite’s life cycle and growth within the cell. This selective advantage of the heterozygote in malaria-endemic regions is why the HbS allele, despite its severe consequences when homozygous, is maintained at high frequencies in those specific populations.
Another proposed case involves the gene responsible for Cystic Fibrosis (CF), known as CFTR. The mutant CFTR allele, common in populations of European descent, is hypothesized to offer protection against certain infectious diseases. Individuals heterozygous for the CFTR mutation are thought to have some resistance to the severe secretory diarrhea caused by cholera and possibly against typhoid fever.
The CFTR mutation reduces the number of functional proteins, which may limit the ability of the cholera toxin to cause excessive fluid loss or prevent the entry of the Salmonella typhi bacteria. While the selective pressure of typhoid and cholera is still being debated, the underlying principle remains: a beneficial effect in the heterozygote maintains a potentially harmful allele in the gene pool.