In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1 alleles. This is an example of recessive epistasis and demonstrates that most biological systems involve many genetic elements that interact in multiple and complex ways.
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The expression of a gene might depend on a gene product in the same biochemical pathway.
One example of epistasis is fur pigmentation in rabbits. Many genes affect a rabbit’s fur color, including one called tyrosinase (TYR). Animals homozygous dominant or heterozygous at a tyrosinase locus will produce colored coats, while homozygous recessive rabbits develop unpigmented coats that appear white. Fur color is also partially established by another gene called tyrosinase-related protein 1, or TYRP1. The dominant allele produces black fur, and the recessive allele produces brown or chocolate fur.
Disregarding other factors involved in coat color, rabbits heterozygous at both loci will have black fur. However, their offspring that inherit two recessive tyrosinase alleles will have white, unpigmented fur, regardless of which TYRP1 alleles they inherit. This is an example of recessive epistasis because the recessive TYR alleles mask or interfere with the production of a black or brown coat. In this case, TYR is epistatic to TYRP1.
The study of epistatic interactions allows researchers to understand how different species developed coat colors to suit unique environments. In general terms, it helps determine the functional relationship between genes, the ordering of genes in a pathway, and how different alleles quantitatively impact phenotypes. As such, since the concept of epistasis was introduced, it has become increasingly clear that most biological systems involve many genetic elements that interact with one another in multiple and complex ways.
