Lethal Alleles

An allele that results in the death of an organism is called a lethal allele. Lethal alleles always involve essential genes, which are necessary for an organism’s survival.

When a mutation is caused by a dominant lethal allele, both homozygotes and heterozygotes that inherit the allele perish.

Dominant lethal alleles are rarely identified in populations because the affected individuals are often eliminated rapidly. A notable exception to this observation is Huntington’s disease, a neurological disorder that ultimately leads to death.

However, the onset of disease doesn’t occur until the age of 40. By this time, many affected individuals have already passed their mutant alleles to their progeny.

Unlike dominant lethal alleles, recessive lethal alleles only result in the death of homozygotes.

An example of an essential gene is agouti, which is responsible for determining coat color in mice. Agouti was first studied in 1905 by Lucien Cuénot and is depicted here with capital A for agouti.

Cuénot experimented on the wild-type allele of the agouti gene, which is functional and gives rise to a gray coat color in mice. Such a mouse is called 'agouti' in color.

A mutant allele of the agouti gene is non-functional and results in a yellow coat color in the mouse.

Cuénot crossed two yellow mice and observed 2 yellow mice for every gray mouse, in a ratio of 2:1. This showed that the yellow coat color is a dominant phenotype. Notably, these results did not match Mendel's expected phenotypic ratio of 3:1 for a monohybrid cross.

To identify the genotype of the yellow mice, he performed a test cross where yellow mice were crossed with homozygous wild-type gray mice. Half of the resulting offspring were gray in color, and the other half were yellow, in a ratio of 1:1, which indicated that all the yellow mice were heterozygous and not a single yellow mouse was homozygous.

In 1910, W. E. Castle and C. C. Little demonstrated that when two heterozygotes were crossed, one-quarter of the offspring died during embryonic development.

The failed embryos were homozygous for the mutant agouti-allele suggesting that it is a recessive lethal allele. This explained why Cuénot never observed homozygous yellow mice, and the numbers did not fit a typical Mendelian ratio.