WHAT IS EPISTASIS? (WITH EXAMPLES) - BIOLOGY - 2025

The epistasis, genetics, is the study of the interaction between different genes coding for the same character. That is, it is the manifestation of a trait that arises from the interaction between alleles of genes at different loci.

When we talk about the relationships that establish alleles of the same gene, we refer to allelic relationships. That is, alleles of the same locus or allelomorphic alleles. These are the known interactions of complete dominance, incomplete dominance, codominance and lethality between alleles of the same gene.

The gene for baldness is epistatic to those with red or blonde hair. Thomas Shafee, from Wikimedia Commons

In the relationships between alleles of different loci, on the contrary, we speak of non-allelomorphic alleles. These are the so-called gene interactions, which are all epistatic in some way.

Epistasis allows us to analyze whether the expression of one gene determines the expression of another. In such a case such a gene would be epistatic on the second; the second would be hypostatic on the first. The analysis of epistasis also makes it possible to determine the order in which the genes that define the same phenotype act.

The simplest epistasis analyzes how two different genes interact to confer the same phenotype. But obviously it can be many more genes.

For the analysis of the simple epistasis we will base ourselves on the variations to the proportions of the classic dihybrid crosses. That is, to the modifications of the 9: 3: 3: 1 ratio, and to herself.

The classic phenotypic ratio 9: 3: 3: 1

This proportion arises from the combination of the inheritance analysis of two different characters. That is, it is the product of the combination of two independent phenotypic segregations (3: 1) X (3: 1).

When Mendel analyzed, for example, plant stature or seed color, each character segregated 3 to 1. When he analyzed them together, even if they were two different characters, each one segregated 3 to 1. That is, they were distributed independently.

However, when Mendel analyzed the characters in pairs, they resulted in the well-known phenotypic classes 9, 3, 3, and 1. But these classes were sums of two different characters. And never, neither character affected how the other manifested.

Gametes and proportions in a cross of two genes. Taken from m.wikipedia.org

Deviations that are not such

The previous one was the explanation of the classic Mendelian proportion. Therefore, it is not a case of epistasis. Epistasis studies the cases of inheritance of the same character determined by several genes.

The previous case, or Mendel's second law, was of inheritance of two different characters. Those explained later are true epistatic proportions and involve only non-allelomorphic alleles.

The ratio 9: 3: 3: 1 (double dominant epistasis)

This case is found when the same character presents four different phenotypic manifestations in a ratio of 9: 3: 3: 1. Therefore, it cannot be an allelic (monogenic) interaction like the one that leads to the appearance of four different blood groups in the ABO system.

Let us take as an example the cross between a heterozygous individual with type A blood and a heterozygous individual with type B blood. That is, the cross I ^A i XI ^B i. This would give us a 1: 1: 1: 1 ratio of individuals I ^A i (Type A), I ^A I ^B (Type AB), I ^B i (Type B) and ii (Type O).

On the contrary, a true dominant double epistatic relationship (9: 3: 3: 1) is observed in the form of the rooster comb. There are four phenotypic classes, but in a 9: 3: 3: 1 ratio.

Two genes participate in its determination and manifestation, let's call them R and P. Regardless, the R and P alleles show complete dominance over the r and p alleles, respectively.

From the RrPp X RrPp cross we can obtain the phenotypic classes 9 R_P_, 3 R_pp, 3 rrP_ and 1 rrpp. The symbol "_" means that that allele can be dominant or recessive. The associated phenotype remains the same.

Class 9 R_P_ is represented by roosters with walnut crests, 3 R_pp by roosters with rose crest. Pea crested roosters would be class 3 rrP_; those of the rrpp class have a single crest.

Cockscomb genetically analyzed several times. Taken from maxpixel.net

In double dominant epistasis, each class 3 arises from the dominance effect of the R or P gene. Class 9 is represented by the one in which both R and P dominant alleles manifest. Finally, in class 1 rrpp, the alleles are absent. dominant of both genes.

The 15: 1 ratio (doubled gene action)

In this epistatic interaction, one gene does not suppress the manifestation of another. On the contrary, both genes code for the manifestation of the same trait, but without additive effect.

Therefore, the presence of at least one dominant allele of either of the two genes from different loci allows the manifestation of the trait in class 15. The absence of dominant alleles (the double recessive class) determines the phenotype of class 1.

The products of the A and / or B genes participate in the manifestation of the color of the wheat grain. That is, either of these products (or both) can lead to the biochemical reaction that transforms the precursor into a pigment.

The only class that does not produce any of them is class 1 aabb. Therefore, classes 9 A_B_, 3 A_bb and 3 aaB_ will produce pigmented grains, and the remaining minority will not.

The 13: 3 ratio (dominant suppression)

Here we find a case of dominant deletion of a gene (hypostatic) due to the presence of at least one dominant allele of the other (epistatic). That is, formally speaking, one gene suppresses the action of the other.

If it is the dominant suppression of D over K, we would have the same phenotype associated with classes 9 D_K_, 3 D_kk and 1 ddkk. Class 3 ddK_ would be the only one showing the non-suppressed trait.

The double recessive class is added to classes 9 D_K_ and 3 D_kk because it does not produce what the hypostatic gene K codes for. Not because it is suppressed by D, which is not in any case, but because it does not produce K.

This ratio is sometimes also called dominant and recessive epistasis. The dominant one is that of K over D / d. The recessive epistasis would be that of dd over K / k.

For example, primrose flowers owe their color to the manifestation of two genes. The K gene that codes for the production of the pigment malvidin, and the D gene that codes for the suppression of malvidin.

Only ddKK or ddKk plants (ie class 3 ddK_) will produce malvidin and be blue in color. Any other genotype will give rise to plants with turquoise flowers.

The 9: 7 ratio (doubled recessive epistasis)

In this case, the presence of at least one dominant allele of each gene in the pair is required for the character to manifest. Let's say it's the C and P genes. That is, the homozygous recessive state of one of the genes of the pair (cc or pp) makes the manifestation of the character impossible.

In other words, only class 9 C_P_ has at least one dominant C allele and one dominant P allele. For the trait to manifest, the functional products of the two genes must be present.

This interaction is epistatic because the lack of expression of one gene prevents the other gene from manifesting. It is double, because the converse is also true.

A classic example that illustrates this case is that of the pea flowers. CCpp plants and ccPP plants have white flowers. The CcPp hybrids of the crosses between them have purple flowers.

If two of these dihybrid plants are crossed, we will obtain class 9 C-P_, which will have purple flowers. Classes 3 C_pp, 3 ccP_ and ccpp will be white flowers.

The study of the inheritance of the color of the flowers has helped a lot to understand the epistasis. Taken from maxpixel.net

Other epistatic phenotypic ratios

From the proportion proposed in Mendel's second law, we have other additional cases that deserve to be mentioned.

We call the modified 9: 4: 3 ratio recessive epistasis for good reason. When a gene is homozygous for the recessive gene, it prevents the expression of the other gene - even if it is dominant.

Take as an example the recessive epistasis of genotype aa over those of gene B. Class 9 is the already recognized 9 A_B_. For class 4, class 1 aabb must be added, with the same phenotype, those of class 3 aaB_. Class 3 would be those of class 3 A_bb.

In the epistatic interaction of duplicated genes, the observed phenotypic ratio is 9: 6: 1. All individuals of class 9 A_B_ have at least one allele of each A or B gene. They all have the same phenotype.

On the contrary, in classes 3 A_bb and 3 aaBb, there are only dominant alleles of either A or B. In this case, there is also a single and the same phenotype - but different from the others. Finally, in class 1 aabb no dominant allele of any of the genes is present and represents another phenotype.

Perhaps the most confusing class is the dominant epistasis, which shows the phenotypic ratio 12: 3: 1. Here, the dominance of A (epistatic) over B (hypostatic) causes class 9 A-B_ to join class 3 A_bb.

The phenotype of B will only manifest when A is not present in class 3 aaB_. The double recessive class 1 aabb will manifest neither the phenotype associated with the A / a gene nor with the B / b gene.

Other epistatic phenotypic ratios that do not have a particular name are 7: 6: 3, 3: 6: 3: 4 and 11: 5.

References

1. Brooker, RJ (2017). Genetics: Analysis and Principles. McGraw-Hill Higher Education, New York, NY, USA.
2. Goodenough, UW (1984) Genetics. WB Saunders Co. Ltd, Pkiladelphia, PA, USA.
3. Griffiths, AJF, Wessler, R., Carroll, SB, Doebley, J. (2015). An Introduction to Genetic Analysis (11th ed.). New York: WH Freeman, New York, NY, USA.
4. Miko, I. (2008) Epistasis: Gene interaction and phenotype effects. Nature Education 1: 197. nature.com
5. White, D., Rabago-Smith, M. (2011). Genotype-phenotype associations and human eye color. Journal of Human Genetics, 56: 5-7.
6. Xie, J., Qureshi, AA, Li., Y., Han, J. (2010) ABO blood group and incidence of skin cancer. PLoS ONE, 5: e11972.