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Gene Interactions
Marie Černá
Lecture No 406-H
Mendelian genetics:
1 character = 1 gene
Genes 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 ratio
F2: 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 pigment
Phenotype 1: R-Cl- – red (anthocyan)
Phenotype 2: R-clcl – brown (red + green)
Phenotype 3: rrCl– yellow
Phenotype 4: rrclcl – green (chlorophyll)
1)
2)
x
P
RRClCl
rrclcl
x
RRclcl
rrClCl
F1
RrClcl
F2
R-Cl9
:
R-clcl
3
:
rrCl3
:
rrclcl
1
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 yellow
Gene 2: allele I – lower degree = light yellow
(ivory white)
Phenotype 1: Y-I-, Y-ii – dark yellow
Phenotype 2: yyI– light yellow
Phenotype 3: yyii
– white
1)
2)
x
P
YYII
yyii
x
YYii
yyII
F1
YyIi
F2
Y-I9
:
12
Y-ii
3
:
:
yyI3
:
3
:
yyii
1
1
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 gene
in 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 coloring
Gene 2: allele A – higher degree = violet coloring
Phenotype 1: P-APhenotype 2: P-aa
Phenotype 3: ppA-, ppaa
– violet
– rose
– white
1)
2)
x
P
PPAA
ppaa
x
PPaa
ppAA
F1
PpAa
F2
P-A9
:
9
:
P-aa
3
:
3
:
ppA3
:
4
ppaa
1
Examples of recessive epistasis in human
AB0 system of blood groups
metabolite
Precursor
transferase H
transferase A
antigens
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
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
• Dominant
• Recessive
substrate
Y
-------> P1
I
-------> P2
substrate
B
A
-------> P0 -------> P
Inhibition
It 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 coloring
Gene 2: allele I = inhibits an effect of allele C
Phenotype 1: C-I-, ccI-, ccii
– colorless
Phenotype 2: C-ii
– colored
1)
2)
x
P
CCII
ccii
x
CCii
ccII
F1
CcIi
F2
C-I9
13
:
:
C-ii
3
3
:
ccI3
:
ccii
1
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 into
colored compound
Phenotype 1: C-RPhenotype 2: C-rr, ccR-, ccrr
– red (anthocyan)
– colorless
1)
2)
x
P
CCRR
ccrr
x
CCrr
ccRR
F1
CcRr
F2
C-R9
9
:
C-rr
3
:
:
ccR3
:
ccrr
1
7
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
1)
2)
x
P
T1T1T2T2
t1t1t2t2
x
T1T1t2t2
t1t1T2T2
F1
T1t1T2t2
F2
T1-T29
15
:
T1-t2t2
3
:
:
t1t1T23
:
t 1t 1t 2t 2
1
1
Duplicity cumulative with dominance
character 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)
1)
2)
x
P
P1P1P2P2 p1p1p2p2
x
P1P1p2p2 p1p1P2P2
F1
P1p1P2p2
F2
P1-P29
:
9
:
P1-p2p2
3
:
6
p1p1P23
:
:
p1p1p2p2
1
1
Duplicity cumulative without dominance
character intensity depends on allele number
Caryopsis 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
brown
mulatto
light brown
white
-
4 dominant alleles A1A1A2A2
3 dominant alleles
2 dominant alleles
1 dominant allele
no dominant allele  a1a1a2a2
P
A1A1A2A2 x a1a1a2a2
F1
A1a1A2a2
F2
A1A1A2A2
1
A1A1A2a2
2
A1A1a2a2
1
A1a1A2A2
2
A1a1A2a2
4
A1a1a2a2
2
a1a1A2A2
1
a1a1A2a2
2
a1a1a2a2
1
1
black
:
4
brown
:
6
mulatto
:
4
:
light brown
1
white
Bilateral allele relation of
cooperated genes
Complementarity
Multiplicity
alleles ≥2 genes
R ∩ S
↓ ↓
A1 A2
↘ ↙
A
phenotype
alleles ≥2 genes
T1 ∪ T2
↘ ↙
A
phenotype
GENE INTERACTIONS - SUMMARY
interaction type
phenotype cross ratio in the F2 generation
reciprocal interaction
dominant epistasis
recessive epistasis
inhibition
complementarity
noncumul. duplicity with domin.
cumul. duplicity with domin.
cumul. duplicity without domin.
Mendelian inheritance
9
12
9
13
9
15
9
1
3
3
3
3
7
1
6
4
3
1
4
1
1
6
4
9
3
3
1
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