Gene Interactions

Marie Černá

Lecture No 406-H

Mendelian genetics: 1 character = 1 geneGenes are segregating independently

on each other

Gene interactions:1 character = two or more genes Interaction of two genes

– genotype ratio as in dihybridism – less phenotype classes

Gene Interactions

• Reciprocal interactions• Epistasis - dominant and recessive• Inhibition• Complementarity• Multiplicity

Reciprocal interactions

= Interactions without change of phenotype ratioF2: 9 : 3 : 3 : 1, B1: 1 : 1 : 1 : 1

The identical character can occur in more various independent forms, which of them is determined by one gene.

gene 1 = A1 Phenotype A2 = gene 2

Reciprocal interactions

Product color of paprika:Gene 1: allele R – anthocyan = red coloring Gene 2: allele Cl – chlorophyll degradation =

yellow pigmentPhenotype 1: R-Cl-– red (anthocyan)Phenotype 2: R-clcl – brown (red + green)Phenotype 3: rrCl- – yellowPhenotype 4: rrclcl – green (chlorophyll)

P

1)x

2)x

F1

RRClCl rrclcl RRclcl rrClCl

RrClcl

R-Cl- R-clcl rrCl- rrclcl 9 : 3 : 3 : 1

F2

Epistasis

One of alleles of the epistatic gene suppresses phenotype manifestation of the hypostatic gene.

It is then an unilateral relation - among alleles of two various genes (M > N)- among alleles of more various genes (M > N > R > S)

Dominant Epistasis

- Dominant allele of one gene has epistatic effect.Dominant alleles of both genes allow the same

precursor processing in the same direction, but into different final products.

Epistatic effect will have dominant allele of that of both genes, which can lead by biosynthetic processes to more expressive form of a trait, and by this way will cover an effect of dominant allele of the hypostatic gene.

Dominant Epistasis

Flower color of dahlia: depends on hydroxylation degree of colorless precursor of flavon pigment

Gene 1: allele Y – higher degree = dark yellowGene 2: allele I – lower degree = light yellow

(ivory white)

Phenotype 1: Y-I-, Y-ii – dark yellowPhenotype 2: yyI- – light yellowPhenotype 3: yyii – white

P

1)x

2)x

F1

YYII yyii YYii yyII

YyIi

Y-I- Y-ii yyI- yyii 9 : 3 : 3 : 1

12 : 3 : 1

F2

Examples of dominant epistasis in human

Determination of eye coloring

- depends on type and density of pigment in eye iris

brown coloring (melanin) gene EYCL3 = BEY2 on chr.15

? light-brown, nut coloring gene EYCL2 = BEY1 on chr.15

genes dominant epistatic towards „lipochrome“ gene

green coloring (lipochrome) gene EYCL1 = GEY on chr.19

? 2nd gene

gene dominant hypostatic towards „melanin“ gene

Determination of eye coloring

BEY > GEY

B-G-, B-gg _brown → intensity depends on

quantity of pigment

bbG- _green

bbgg _blue (albinotic) →

inability of pigment formation

Which parents can have which children?

Examples of dominant epistasis in human

Determination of hair coloring

- depends on type and density of pigment in hair fiber

eumelanin = dark dye - black/brown hair

gene HCL3 on chr.15 - association with eye brown coloring

gene BRHC on chr.19 - association with eye green coloring

gene dominant epistatic towards other two genes

pheomelanin = red-and-yellow dye - rusty-red hair

gene RHC on chr.4

gene dominant epistatic towards „blond“ gene

? gene x → low density - blond hair

Determination of hair coloring

HCL3 (BRHC) > RHC > x

H-rr _black (↑ pigment) / brown (↓ pigment)

H-R- _dark-brown

hhR- _rusty-red

hhrrX- _blond

hhrrxx _white (albinotic) →

inability of pigment formation

_grey → degraded products of pigment

Which parents can have which children?

Recessive Epistasis

- Recessive allele of one genein homozygous state has epistatic effect.

Dominant alleles of both interactive genes participate in multistage synthesis of the same final product.

Still dominant allele of the epistatic gene functions in one of initial phases of biosynthesis, while dominant allele of the hypostatic gene functions not until in one of its later phases.

Recessive Epistasis

Flower color of sage: depends on hydroxylation degree of colorless precursor of flavon pigment

Gene 1: allele P – lower degree = rose coloringGene 2: allele A – higher degree = violet coloring

Phenotype 1: P-A- – violetPhenotype 2: P-aa – rosePhenotype 3: ppA-, ppaa – white

P

1)x

2)x

F1

PPAA ppaa PPaa ppAA

PpAa

P-A- P-aa ppA- ppaa 9 : 3 : 3 : 1 9 : 3 : 4

F2

Examples of recessive epistasis in human

AB0 system of blood groups metabolite antigens

Precursor H, A H H, B

H

- (unchanged precursor)

H or h alleles are recessively epistatic

against A or B alleles hh genotype codes the blood group 0

even in the presence of A or B alleles hh = Bombay allele

transferase H transferase A

transferase B

0hh

Recessive epistasis is manifested in the case of the gene for secretion of antigens A, B, H:

Genotypes SS, Ss secret antigens into saliva and body fluids

Genotype ss does not secret any antigens, even though they are present in erythrocytes

Epistasis- unilateral relation

• Dominantsubstrate

Y-------> P1 I-------> P2

• Recessivesubstrate

B A-------> P0 -------> P

InhibitionIt is certain analogy of dominant epistasis.

But, in comparison with it, inhibitive allele I has not another effect on phenotype than ability to suppress an effect of allele A.

Feathers color of domestic fowl: Gene 1: allele C = red coloringGene 2: allele I = inhibits an effect of allele C

Phenotype 1: C-I-, ccI-, ccii – colorlessPhenotype 2: C-ii – colored

P

1)x

2)x

F1

CCII ccii CCii ccII

CcIi

C-I- C-ii ccI- ccii 9 : 3 : 3 : 1 13 : 3

F2

Complementarity and Multiplicity

• genes are equal – no subordination• bilateral relation of alleles of interactive genes

Complementarity is bilateral relation of alleles of interactive genes.• Dominant alleles of complementary genes allow

genesis of two or more non-replaceable components, which form the final product.

• Each of these components is qualitatively different and arises from different biosynthetic processes.

• For this reason replacement of any of dominant alleles of complementary genes for recessive one leads to non-formation of the final product.

Complementarity

Flower color of earthnut pea: Gene 1: allele C – formation of colorless precursor Gene 2: allele R – formation of activation enzyme,

which changes the precursor intocolored compound

Phenotype 1: C-R- – red (anthocyan)Phenotype 2: C-rr, ccR-, ccrr – colorless

P

1)x

2)x

F1

CCRR ccrr CCrr ccRR

CcRr

C-R- C-rr ccR- ccrr 9 : 3 : 3 : 1 9 : 7

F2

Multiplicity

is bilateral relation of alleles of interactive genes,but in comparison with complementarity,

each single dominant allele of any of these genes, even in itself, is sufficient for expression of a corresponding trait.

To this effect these single dominant alleles are identical. These alleles are responsible for biosynthesis of identical final products, but by qualitatively different ways.

Multiplicity

• Noncumulative – full expression of a corresponding trait is caused by single dominant allele of given multiplicative rank and presence of next members of the rank no more changes intensity of phenotype.

• Cumulative – intensity of phenotype expression is direct proportionally dependent on number of present dominant members of multiplicative rank.

Duplicity noncumulative

Siliqua shape of shepherd’s purse: Gene 1: allele T1 – normal (heart-shaped)

Gene 2: allele T2 – normal (heart-shaped)

T1+T2 – normal (heart-shaped)

Phenotype 1: T1-T2-, T1-t2t2, t1t1T2- – normal

Phenotype 2: t1t1t2t2 – cylindrical

P

1)x

2)x

F1

T1T1T2T2 t1t1t2t2 T1T1t2t2 t1t1T2T2

T1t1T2t2

T1-T2- T1-t2t2 t1t1T2- t1t1t2t2

9 : 3 : 3 : 1 15 : 1

F2

Duplicity cumulative with dominancecharacter intensity depends on gene number

Caryopsis color of barley: Gene 1: allele P1 – brownish red coloring (half)

Gene 2: allele P2 – brownish red coloring (half)

P1+P2 – dark brown coloring (maximal)

Phenotype 1: P1-P2- – maximal

Phenotype 2: P1-p2p2, p1p1P2- – half

Phenotype 3: p1p1p2p2 – null (white)

P

1)x

2)x

F1

P1P1P2P2 p1p1p2p2 P1P1p2p2 p1p1P2P2

P1p1P2p2

P1-P2- P1-p2p2 p1p1P2- p1p1p2p2

9 : 3 : 3 : 1 9 : 6 : 1

F2

Duplicity cumulative without dominance character intensity depends on allele numberCaryopsis color of wheat: Gene 1: allele R1 – pink coloring (quarter)

Gene 2: allele R2 – pink coloring (quarter)

Phenotype 1: R1R1R2R2 – dark red (maximal)

Phenotype 2: R1R1R2r2, R1r1R2R2 – red (three quarter)

Phenotype 3: R1R1r2r2, R1r1R2r2, r1r1R2R2 – rose (half)

Phenotype 4: R1r1r2r2, r1r1R2r2 – pink (quarter)

Phenotype 5: r1r1r2r2 – white (null)

Davenport’s hypothesis

about pigment synthesis in human:Degree of pigmentation is coded by the number of dominant alleles of 2 allelic pairs / genes

• black - 4 dominant alleles A1A1A2A2• brown - 3 dominant alleles • mulatto - 2 dominant alleles• light brown - 1 dominant allele• white - no dominant allele a1a1a2a2

P A1A1A2A2 x a1a1a2a2

F1 A1a1A2a2

F2

A1A1A2A21

A1A1A2a22

A1A1a2a21

A1a1A2A22

A1a1A2a24

A1a1a2a22

a1a1A2A21

a1a1A2a22

a1a1a2a21

1 : 4 : 6 : 4 : 1

black brown mulatto light brown white

Bilateral allele relation of cooperated genes

Complementarityalleles ≥2 genes

R ∩ S↓ ↓A1 A2↘ ↙

Aphenotype

Multiplicityalleles ≥2 genes

T1 ∪ T2

↘ ↙A

phenotype

GENE INTERACTIONS - SUMMARYGENE INTERACTIONS - SUMMARY

interaction type phenotype cross ratio in the F2 generation

reciprocal interaction 9 3 3 1

dominant epistasis 12 3 1

recessive epistasis 9 3 4

inhibition 13 3

complementarity 9 7

noncumul. duplicity with domin. 15 1

cumul. duplicity with domin. 9 6 1

cumul. duplicity without domin. 1 4 6 4 1

Mendelian inheritance 9 3 3 1

Significance of gene interactions in multifactorial diseases

• the main genetic mechanism of

predisposition to diseases

Principle of cumulative multiplicity = heredity of quantitative traits - polygenic heredity

Significance of gene interactions in monogenic diseases

• low penetrance penetrance = probability of expression of dominant allele in phenotype

- sick or healthy persons

• different expressivity

expressivity= intensity of phenotype manifestation

- severe or minor clinical signs