Principles of Genetics (BIOL2250)

Department of Biology
Memorial University of Newfoundland

"Gene Interactions (continued)"

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.

Suppressor Genes

A suppressor is an allele of a gene that reverses the effect of a mutation of another gene.
Suppressors can act in homozygous recessive manner (su/su) or as a dominant (Su _).
Suppressors result in a modified dihybrid ratio (13:3 instead of 9:3:3:1).
For example, a mutant allele of the gene purple (pu) results in purple eyes instead of red in Drosophila melanogaster.
Another gene, suppressor of purple su(pu) exists which, when homozygous su(pu)/ su(pu), will suppress homozygous purple (pu/pu).
In other words, a pu/pu individual has purple eyes unless the fly also is homozygous for the mutant version of the suppressor gene (su(pu)/ su(pu)).
The suppressor alleles of the gene often have no phenotypic effect in the absence of the suppressible mutant genes.
The recessive homozygote su(pu)/ su(pu),appears to be wild type in nature.

G0  pu+/pu+; su(pu)/ su(pu)  X pu/pu; su(pu)+/ su(pu)+
                        F1  pu+/pu; su(pu)+/ su(pu)
                    9 pu+ ___; su(pu)+/ ____ red
                    3 pu+ ___; su(pu)/ su(pu) red
                    3 pu/pu; su(pu)+/ ____ purple

                    1 pu/pu; su(pu)/ su(pu) red (purple is suppressed)

So instead of a 12:4 (3:1) ratio, supression results in a 13:3 modified dihybrid ratio.
Suppression differs from epistasis in that suppression cancels (not masks) the effect of an other mutation resulting in two (not three phenotypes).

Some mutations (nonsense mutations) are caused by changes in the DNA sequence that result in the premature stoppage of the translation of a protein at a nonsense translation termination codon.
One mechanism of suppression is demonstrated by the nonsense suppressor mutation which relies upon a compensatory mutation in a tRNA anticodon to insert an amino acid into a nonsense translation termination codon.

Suppression may also be based upon protein-protein interactions.
A mutation may result in a protein that is "bent" into an abnormal shape.
Proteins that normally interact or bind this protein may not interact with the abnormally bent mutant form.
A mutation in the gene that encode the second protein may restore the interaction and thus supress the effects of the initial mutation.

In summary, suppressors cancel the expression of a mutant allele of another gene resulting in normal wild-type phenotype.

Duplicate Genes

Duplicate genes provide alternative genetic determination of a specific phenotype.
If two identical or nearly identical copies of the same gene exist in the genome of an organism, both copies must be mutated before an effect is observed.
In this case, an individual must be doubly homozygous to give the mutant phenotype.
In a dihybrid cross of such individuals, a modified 9:3:3:1 ratio of 15:1 is observed.

G0   a a a2+ a2+  X  a1+ a1+ a a2

                F1    a1+ a1 a2+ a2

            9  a1+ __   a2+ __ (wild type)
            3  a1   a1   a2+ __ (wild type)
            3  a1+ __   a2 a2 (wild type)
            1  a  a1   a2  a2 (mutant)

or 15 (wild type) to 1 (mutant)

Homework Assignment:

Work through the relationships between D/d; M/m; and W/w in foxglove petals and the results of the genetic interactions between these genes (p119-120).

Gene interaction  in coat colour of mammals

Agouti (A) gene is responsible for the "salt and pepper" brindle colour of many wild mammals.  An agouti hair has a band of yellow on the shaft of the hair.

Black (B) gene controls the colour of the pigment where B _ is black and bb is brown.

Colour (C) gene  permits colour expression while cc results in an albino.
Note that Himalayan alleles of this gene (ch) are found in many mammals including mice, cats and rabbits.

Colour intensity (D) gene determines the intensity of the colour such that D _ permits full expression of the colour while dd results in a diluted or milky version of the colour.
Alleles of the colour intensity alleles interact with other genes in horses to give two series of coat colours: 1) chestnut (DD), palomino (Dd) and cremello (dd) and 2) bay (DD), buckskin (Dd) and perlino (dd).

Colour distribution (S) gene which prevents spots when S _  and allows the formation of spots when ss.

A_ B_ = agouti
A_ bb = cinnamon
aa B_ = black
aa bb = brown

_ _ cc = albino

B_ dd dilute black
bb dd dilute brown

Homework Assignment:

Workout the phenotypes of dihybrid and trihybrid crosses with several of these genes.

Penetrance and Expressivity

Different kinds of modified dihybrid ratios point to different ways in which genes can interact with each other to determine phenotype
Penetrance is the percentage of individuals with a given genotype who exhibit the phenotype "associated" with that genotype.
Environmental factors, epistatic genes, suppressors or other modifiers may contribute to an organism not exhibiting the given phenotype.

Expressivity measures the extent to which a given genotype is expressed in the phenotype (the variability of a trait based upon a specific genotype).

Pentrance and expressivity describe the modificiation of gene expression by varying environmental and genetic backgrounds.

The Chi-square test

To determine if an observed set of data is compatible with a predictions based on a hypothesis, a simple statistical method, the Chi-square test can be used.

Observed (O) and Expected (E) values are compared.
The sum of (O-E)2/E for all classes is compared to a table of values.
The degrees of freedom (df) depends upon the number (n) of classes (df=n-1).
The deviation of experimental numbers from the expected would be expected to occur as frequently as the table indicates.
Values of less than 5% (P=0.05) indicates that the hypothesis is unlikely and should be rejected.

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