Mendel's First Law

Pleiotropy

## Pleiotropic Effects and Lethal Genes

During the first years after the rediscovery of Mendel's laws, a number of experiments were performed that gave results that at first glance did not coincide with the laws. In 1904, a cross was made between a yellow-coated mouse and a mouse with a gray coat. The gray- coated mouse was extensively inbred and therefore was considered to be pure bred.

What allelic relationship do we have here? We know that the gray mouse is homozygous (because it is a pure line). If gray coat was dominant then we would see all gray mouse. Since we obtain both yellow and gray mice, yellow must be dominant to gray. So what are the genotypes of the two mice populations? First, let's provide gene symbols.

 Gene Symbols: gray = yyellow = Y

From the above discussion, the genotype of the gray mouse must be yy. What is the genotype of the yellow mouse? If the mouse was homozygous we would not see any gray mice from the cross, therefore the genotype must be heterozygous or Yy.

Next a cross was made between two yellow mice. What genetic ratio would we expect to see? Yy x Yy should give a ratio of 3 yellow:1 gray. The result, though, was a ratio of 2 yellow to 1 gray mice. How can this result be explained? Let's first set up a Punnett Square.

Expected Punnett Square

 Female Gametes MaleGametes Y y Y YY (yellow) Yy (yellow) y Yy (yellow) yy (gray)

As we can see, we should get a 3:1 ratio of yellow to gray mice. Could some genotype be absent from the progeny. How can we test the genotypes of the yellow mice, since we already know the genotypes of the gray mice are yy. Testcross!! All testcross data with the yellow mice give a 1:1 ratio. This ratio is typical of what is seen with heterozygous individuals. Therefore, all of the yellow mice from the cross of two heterozygous yellow mice are genotypically Yy. Somehow the YY genotype is lethal. The 2:1 ratio is the typical ratio for a lethal gene.

Coat Color in Mice

Lethal Gene - a gene that leads to the death of an individual; these can be either dominant or recessive in nature

An important question is how can a gene controlling coat color cause death in an organism? Possibly in a single dose the allele causes a yellowing of the coat, but when expressed in two doses, the gene product kills the animal. Thus, this gene actually has an effect on two phenotypes.

Pleiotropic gene - a gene that affects more than one phenotype

In this example the gene that causes yellowing of the coat also affects viability and is termed a pleiotropic gene.