SB 4: Ch 2.2 Extensions to Mendel for Two-Gene Inheritance

Two genes can interact in several ways to determine a single trait

Additive interactions between two genes can create novel phenotypes, how does this compare to Mendel’s?

• PB tan (AAbb) x PB gray (aaBB) lentils

  • F1 = hybrid brown (AaBb)

  • F2 = 9 brown: 3 tan: 3 gray: 1 green

• Same 9:3:3:1 but here: two genes interact additively to control one single trait — seed color

• With complete dominance at both genes, the 9 possible F₂ genotypes collapse into only 4 phenotypic classes

• With incomplete dominance or codominance, the F₂ genotypes could instead produce more than four phenotypes

Biochemical/Molecular explanation for the interaction of 2 genes for 1 trait

• The two genes likely encode proteins that act additively in independent biochemical pathways

• Enzyme A (AA, Aa) gives tan; Enzyme B (BB, Bb) gives gray; both together (both dominant) give brown; if neither (aabb), then green

• This is why heterozygous/dominant combinations at both loci produce a new phenotype (brown) rather than blending or one trait masking the other

Epistasis Definition/Terms

• One gene can mask the effect of another

• Fewer than four phenotypes because one gene hides the effects of another

  • This masking interaction = epistasis

  • The gene doing the masking = epistatic

  • The gene being masked = hypostatic

Recessive Epistasis

• Occurs when homozygosity for a recessive allele of one gene hides the effect of the other

• When an individual is homozygous for the epistatic recessive allele of one gene, the whole phenotype is independent of whatever alleles are present at the hypostatic gene (other gene) Rec

Recessive Epistasis Ratio, Biochemistry, & Labrador Example

• Two genes involved: B gene and E gene

• Pure-breeding black (BBEE) × pure-breeding yellow (bbee)

  • F1 = black (BbEe)

  • F2 = 9 black (B-E-): 3 brown (bbE-): 4 yellow (-ee)

• 9:3:4 ratio

• 3 B-ee + 1 bbee = 4 —ee

• The ee genotype masks the influence of the B gene on coat color (epistatic gene = E; hypostatic gene = B)

• Underlying biochemistry: B and E gene products act in the same coat-color pathway; the product of one enzyme helps with the product of the other (final product)

Recessive Epistasis - Bombay Phenotype

• The superficial resemblance of O from hh

• Type A: enzyme adds polysaccharide A onto sugar polymer substance H

• Type B: an alternate enzyme adds polysaccharide B onto sugar polymer substance H

• Type O: neither added, exposed substance H

• ABO genes all carry at least one H allele and produce H substance. In the Bombay phenotype (hh), no H is produced, nothing for an enzyme to add onto, so it appears O

• hh alleles of H gene masks ABO gene

How can a parent of blood type O and a parent of blood type B have an offspring that is blood type A?

• Parent appears to be blood type O (predicted genotype ii)

  • Could actually be AB, hh each

  • Or Ai, hh

  • Donates an A

Reciprocal Recessive Epistasis

• 9:7 ratio

• 9 A-B- and 7 are (3) A-bb, (3) aa-B, and (1) aabb

• Need both Enzyme A and Enzyme B to make pigment, even if one works, both are needed as precursors

Reciprocal Dominant Epistasis

• 15:1

• Dominance of one gene masks the other

• Redundant Gene Action: A and B act in parallel, redundant pathways, specify identical proteins

  • Dominant Epistasis usually indicates that the dominant alleles of 2 genes have antagonistic functions

Incomplete Dominance/Codominance

• 4 genotype classes, 9 genotypes

• Expands the number of phenotypes

Locus heterogenity

• Mutations in any one of several genes may cause the same phenotype

• Example: 50 genes have alleles that cause deafness; many genes contribute to the developmental pathway of hearing

  • Dominant wild-type of each gene gives normal hearing

  • Heterogenous trait

What is a complementation test used for and how is it done?

• To determine whether an identical recessive mutant phenotype in two different breeding lines is caused by mutations in the same gene or different genes.

• Mate affected individuals from the two lines together and observe the phenotype of the offspring.

Complementation Occurs

• Offspring show the wild-type phenotype (normal)

• The two mutations are in different genes. Each parent's normal (wild-type) allele of one gene "complements" — makes up for — the other parent's mutant allele at that same gene.

• So the offspring end up with at least one functional copy of both genes.

No Complementation Occurs

• The two mutations are in the same gene.

• Neither parent can supply a functional allele the other lacks — the offspring is homozygous mutant (received one nonfunctional allele of that gene from each parent) → still mutant.

Two key conditions for complementation to be meaningful

1. The mutant alleles must be recessive

2. The mutant alleles must be nonfunctional (loss-of-function)
   — i.e., complementation only makes sense if a single dose of the normal allele can restore the phenotype.

What does a successful complementation result tell you about the trait?

The trait must be heterogeneous — meaning more than one gene can independently cause the same phenotype when mutated.