6 - Molecular basis of gene interaction

Epistasis - the interaction between two or more genes to control a single phenotype 

Polygenic inheritance (interaction between genes) 

• Genes rarely act independently of each other 

Genes usually cooperate in the production of a trait: 

• Formation of molecular complexes 

• Formation of molecular pathways eg. cell signalling

Function of one gene can mask or modify the function of another cooperating gene (epistasis): 

• Protein of one gene may stimulate or repress another gene and its protein 

• Absence of a functional gene (eg. through mutation) often affects the function of another gene and its protein 

Eg. two genes acting on the same colour trait in tomatoes: 

• Red pigment requires R1 and R2 products 

• Yellow pigment requires R1 

• Lack of R1 will give green 

• Epistasis occurs when one gene masks the effects of another gene acting on the same trait

• Epistatic = doing the masking (eg. R1 is epistatic to R2) 

• Hypostatic = masked gene 

• Epistatic ratios mat allow a geneticist to determine the order of genes in a particular pathway 

Coat colour in mice 

• One recessive gene (c ) can mask all the other colour coding genes

• Trihybrid cross - AaBbCc x AaBbCc 

• A and B give a different coat colour

• The agouti gene C is dominant  

• When C is a wild type complex relationship between A and B segregating as 9:3:3:1 

• But when c is homozygous mutant, coat colour is white ie. when the genotype is A_B_cc or aabbcc

• C masks the effects of the other 2 genes; it could code for a precursor or makes a precursor that A and B act on 

• Within dihybrid F1 crosses can find epistatic relationships that can give modified 9:3:3:1 ratios 

• 12:3:1 = dominant epistasis 

• 9:7 = complementary gene action 

• 15:1 = duplicate gene action 

• 13:3 = dominant suppression epistasis 

Dominant epistasis 

• 12:3:1 

• Dominant allele of one gene masks the effect of both alleles of another gene 

Example: 

• If you are B_ you're white 

• If you are bb, colour is determined by A/a 

• A_ is yellow 

• aa is green 

• B is epistatic to A and a 

Complementary gene action 

• 9:7 

Eg. two genes are needed to produce flower colour 

Perform a cross between double homozygotes: 

What is the ratio of pink : white in the F2? 

9:7 

• Need at least one wild type allele for both genes, otherwise white 

Duplicate gene action 

• 15:1 

• Double dominant alleles, two genes working on the same part of a pathway

• Genes don't have to work in opposition for interaction to be epistatic 

Eg. Kernel colour in wheat

Cross AABB (coloured) x aabb (colourless

Cross the F1s (AaBb) 

15:1

• Because either of the genes can produce a wild type phenotype 

Dominant suppression epistasis 

• 13:3

• Some genes have the ability to suppress the expression of a gene at a second locus 

• Suppressor - a genetic factor that prevents the expression of alleles at a second locus; this is an example of an epistatic interaction

Eg. Production of the chemical Malvidin in the plant Primula 

• Synthesis of malvidin (controlled by K gene) and the suppression of synthesis at the K gene (controlled by D gene) are dominant traits 

• The F1 plant with the genotype KkDd will not produce malvidin because of the presence of the dominant D allele 

Distribution of the F2 phenotypes after the F1 were crossed

Human example of epistasis 

Bombay phenotype 

• Involves the interaction between the ABO alleles and a third antigen H coded for by a different gene (H) 

• Individuals homozygous recessive at the H gene (hh) will be blood type O regardless of the phenotype of the I-gene which has the alleles for the AB blood types 

• H codes for an antigen H that is the precursor molecule for the formation of the A and B antigens 

• Genetically, individuals may be A, B or AB but appear as O if the are hh 

• Can't make A or B without H