Heterozygote Advantage - Experimental Confirmation

Experimental Confirmation

Cases of heterozygote advantage have been demonstrated in several organisms, including humans. The first experimental confirmation of heterozygote advantage was with Drosophila melanogaster, a fruit fly that has been a model organism for genetic research. In a classic study, Kalmus demonstrated how polymorphism can persist in a population through heterozygote advantage.

Kalmus discovered a mutant allele of an autosomal gene that expressed ebony body color and other selective advantages in a pattern that was autosomal dominant. The same allele also conveyed harsh disadvantages in a pattern that was completely recessive. When a fly inherited two copies of the mutation (homozygous), it expressed the dark ebony color, but it was also particularly weak, and was placed at a harsh reproductive disadvantage.

If weakness were the only effect of the mutant allele, so it conveyed only disadvantages, natural selection would weed out this version of the gene until it became extinct from the population. However, the same mutation also conveyed advantages, providing improved viability for heterozygous individuals. The heterozygote expressed none of the disadvantages of homozygotes, yet gained improved viability. The homozygote wild type was perfectly healthy, but did not possess the improved viability of the heterozygote, and was thus at a disadvantage compared to the heterozygote in survival and reproduction.

This mutation, which at first glance appeared to be harmful, conferred enough of an advantage to heterozygotes to make it beneficial, so that it remained at dynamic equilibrium in the gene pool. Kalmus introduced flies with the ebony mutation to a wild-type population. The ebony allele persisted through many generations of flies in the study, at genotype frequencies that varied from 8% to 30%. In experimental populations, the ebony allele was more prevalent and therefore advantageous when flies were raised at low, dry temperatures, but less so in warm, moist environments.