Principles of Genetics (BIOL2250)

Department of Biology
Memorial University of Newfoundland

"Gene Interactions"

One of the unfortunate aspects of genetic studies is that we usually only consider one, or at best a few, genes and ignore the tens of thousands of other genes that are present in the individuals crossed.
The relationships of genes to phenotypes can be complex.

Pleiotropy

One gene may influence many phenotypes.
Pleiotropy describes the effect of a single mutant gene (or gene pair) upon a number of characteristics.
For example, a mutation in a gene responsible for pigment production (such as white [w] in Drosophila) may cause various tissues to display altered pigmentation.

In contrast, there are often many genes that contribute to a specific phenotype.
There are greater than 100 genes that are involved in the production of pigment in the Drosophila compound eye.
 

Complementation

This is a complementation test, the diagnostic test for allelism, is to cross two individuals that bear identical or similar mutant phenotypes together.
If the mutations are in alleles of the same gene, the F1 will display the mutant phenotype.
If the mutations are in alleles of different genes, the F1 will NOT display the mutant phenotype.
Complementation is the production of a wild type phenotype when two haploid genomes bearing different recessive mutations are united in the same cell.
Failure to complement, indicates that the parents carried mutations in the same gene.
In summary, when two independently derived recessive mutant alleles producing similar recessive phenotypes fail to complement the alleles must be of the same gene.
 

Example of Complementation Testing

Armed with the knowledge that white feather colour is recessive, a chicken farmer with different breeds of white chickens decides to test if the white colour is caused by defective copies of the same gene in each line.

1) White strain A crossed to white strain B produces all white offspring.

(a a X a' a' -> a a')

This indicates that the mutation in both cases is in the same gene.

2) White strain A crossed to white strain C produces all black & brown offspring.
This indicates that the mutation in both cases is in different genes.

aa X bb  (aa b+b+ X a+a+ bb) -> a+a b+b


Question: What would the cross between white strain B and white strain C produce?

Basis of Complementation

The production of pigment usually requires a number of enzymatic reactions involving a number of precursors and intermediate products.
 

precursors  ---enzyme 1 -- > intermediate ---enzyme 2 -- > intermediate (-etc -) - > pigment

The enzymes are encoded by one or more genes, each directing a step in the process.

In haploid organisms, such as fungi, complementation can occur in the diploid heterokaryon when two nuclei share a common cytoplasm.
 

Intra-allelic Interactions

Alleles of the same gene can display functional interactions that result in very different phenotypes depending upon the alleles involved.

Incomplete dominance is when the heteroallelic combination of two alleles results in a phenotype that is intermediate between the two homoallelic combinations.
In some flowers, c+c+ petals are red and c'c' petals are white.
However, instead of one or the other being completely dominant, the heterozygote c+c' is pink.
Similarly, in Shorthorn cattle, the offspring of a red Shorthorn and a white Shorthorn is a roan (a mixture of red and white hair).
In Shorthorns cattle,  r+r+ is red coated, r'r' is white and r+r' is roan.

If an allele is completely dominant, one copy (instead of two doses) of a gene will produce enough gene product to give normal function.
In other words, half of the gene dosage is sufficient : the gene is haplosufficient.
Rarely, this is not true (and half of the gene dosage is NOT sufficient ): the gene is said to be haploinsufficient.

Codominance occurs when two alleles produce different products.
In the human ABO blood groups an individual may carry up to two alleles of the gene I (IA  IB,  or i).
Genotype  Blood Type
IA  IA  or IA  i A
 I I or IB i B
IA  IB AB
i i  O

Remember that the type of dominance is determined by the molecular functions of the alleles of a gene and by the investigative level of analysis.
Sickle cell anemia is a recessive disease (HbS HbS).
In heterozygotes which have abnormal red blood cells under some conditions (the Sickle Cell Trait), reveal a codominant presence of different forms of the hemoglobin.
Electrophoresis (separation of molecules in a solid support (eg. gel) by electrical current) of the blood cell proteins show the two different forms of hemoglobin.

Allelic Series

A gene can have several different states or forms (multiple alleles).
The alleles are said to constitute an allelic series and the members of a series can show various degrees of dominance to one another.
The markings on the leaves of clover are based upon an allelic series of one gene that produces a wide range of pattern phenotypes.

Lethal alleles

Some mutations cause death during development when homozygous.

Homework Assignment:

Outline the pattern of inheritance of an allele that is an unconditional Dominant Lethal!

The gene yellow (in mice) show unusual patterns of inheritance.
A)  Yellow mice crossed to wild type mice give a 1 yellow to 1 wild type (1:1) ratio in the progeny.
Yellow fur is due to a single dominant allele of a gene.

A AY (yellow) X A A (wild type) - > 1 A AY (yellow) : 1 A A (wild type).


B) Yellow mice crossed yellow mice give 2 yellow to 1 wild type (2:1) ratio and no true breeding line of this allele of yellow mice exists.
 

A AY (yellow) X A AY (yellow) - >  2 A AY (yellow) : 1 A A (wild type).


Note that the AY AY class is missing from the 1:2:1 ratio.
 

A AY(yellow) X A AY(yellow) - > 1 AYAY lethal:  2 A AY(yellow) : 1 A A (wild type).


AY is a pleiotropic allele which affects both colour and viability.

Similarly, in domestic cats the tailless Manx phenotype is due to a dominant allele ML of a gene that severely disrupts spinal development.
 

Gene interaction and modified dihybrid ratios

A classical example of interacting genes from different biochemical pathways concerns the formation of two pigments in the corn snake.
Alleles of two genes interact to produce the natural camouflaged pattern, orange, black  and albino in a 9:3:3:1 pattern in dihybrid crosses.

Mutations with the same phenotype

Interacting genes in same pathway will produce a modified (9:3:3:1) ratio.

precursors  ---enzyme 1 -- > intermediate ---enzyme 2 -- > final product

The a+ allele encodes enzyme 1 and the b+ allele encodes enzyme 2

a a b+ b+  X  a+ a+ b b

If mutant alleles exist for genes controlling two steps in the same biochemical pathway, recessive homozygotes for either gene may display the same null phenotype.
Interacting genes in same pathway with the same mutant phenotype will produce a modified (9:3:3:1) ratio of 9:7.
 

Epistasis (masking mutant allele effects)

If mutant alleles exist for genes controlling two steps in the same biochemical pathway, recessive homozygotes for one gene may mask the effects of another.
Interacting genes in same pathway with different mutant phenotypes may produce a modified (9:3:3:1) ratio of 9:3:4
Epistasis points to interaction of genes in some biochemical or developmental sequence.
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