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Complications to Mendel: Gene Interactions
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From Genotype to Phenotype
a. vaculolar pH = 6.6
b. vacuolar pH = 7.7
This is a single gene trait. The coloration of the flowers depends on the:
• production of the appropriate anthocyanin pigments
• presence of metal ions and co-pigments
• the vacuolar pH in epidermal cells
These wild-type (b) and mutant (a) morning glories produce exactly the same anthocyanin
pigment in their petals. The phenotypic difference in the two plants is due to a single gene
difference: the flower on the left has a recessive, loss-of-function mutation in a gene that codes for a
Na+/H+ exchanger. This mutation results in a decrease in the vacuolar pH of epidermal cells
causing the petals to appear purple rather than blue.
Using genetical conventions, we would name the gene defined by this phenotypic variation the
purple gene and assign the following allele symbols: p+ = blue p = purple
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The art and genetics of color
in plants and animals
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Are these examples of color variation single gene traits? In other words, can a
single gene (perhaps with multiple alleles and complications to dominance)
explain color variation in budgie parakeets or in bell peppers?
3
The table below shows the results of crossing true-breeding
lines of green, blue, yellow and white budgies.
parents Green Blue Yellow White
Green
green
green green
green
Blue
green
blue
blue
green
Yellow green
green yellow
yellow
White
blue
white
green
yellow
Number of
genes?
Number of
alleles?
Dominance?
Possibilities:
• One gene: four alleles; dominance complete
• One gene: three alleles; some incomplete dom
• Two genes: two alleles; dominance complete
• Three or more genes
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P true-breeding yellow X true-breeding blue
â
F1 green X
F1 green
â
F2 9/16 green 3/16 blue 3/16 yellow 1/16 white
How many genes involved?
Speculate about genotypes using elementary principles of
combining colors
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Additive Gene Effects
• independent, additive contribution to phenotype: effects of the alleles of the
two loci are essentially the sum of the independent gene actions
• unmodified Mendelian ratio: AaBb X AaBb à 9:3:3:1 (two genes; each gene
has two alleles, complete dominance)
• essentially there is no gene interaction – the genotype at one gene locus
doesn’t affect the expression/function of the alleles at a second gene locus
Yellow and blue
pigments are
synthesized in
independent
biochemical
pathways. A
(mutational)
disruption in one
pathway does not
affect the other
pathway
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See also this beautiful
example of additive gene
effects in corn snakes
(Chapter 6 of text)
Two genes independently
controlling the synthesis of
two different pigments;
each gene has two alleles
showing complete
dominance
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The complicated relationship between genes and phenotypes
Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes
2 OCTOBER 2009 VOL 326 SCIENCE
Coat color and type are essential characteristics of domestic dog breeds.
Although the genetic basis of coat color has been well characterized,
relatively little is known about the genes influencing coat growth
pattern, length, and curl. We performed genome-wide association
studies of more than 1000 dogs from 80 domestic breeds to identify
genes associated with canine fur phenotypes. Taking advantage of both
inter- and intrabreed variability, we identified distinct mutations in three
genes, RSPO2, FGF5, and KRT71 (encoding R-spondin–2, fibroblast
growth factor–5, and keratin-71, respectively), that together account for
most coat phenotypes in purebred dogs in the United States. Thus, an
array of varied and seemingly complex phenotypes can be reduced to
the combinatorial effects of only a few genes.
See Figure on the next page:
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- represents ancestral
allele (found in
wolves)
+ = variant allele
3 genes, 2 alleles
(complete dominance)
7 out of 8 combos are
shown here
Which is missing?
furnishings= moustache and large eyebrows
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Additive gene effects: RECAP
• independent, additive contribution to phenotype: effects of the alleles
of the two loci are essentially the sum of the independent gene actions
• unmodified Mendelian ratio: AaBb X AaBb à 9:3:3:1
• no interaction of the alleles – the genotype at one gene locus doesn’t
affect the expression/function of the alleles at a second gene locus
Gene Interactions: Specific alleles of one gene mask or modify
(enhance, suppress or in some way alter) the expression of alleles of a
second gene
• complementary gene action
• epistatic gene interaction
• modifiers & suppressors
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Gene Interactions: Specific alleles of one
gene mask or modify (enhance, suppress or
in some way alter) the expression of alleles
of a second gene
• complementary gene action
• epistatic gene interaction
• modifiers & suppressors
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Complementary Gene Action
Both John
and Karen
are deaf
due to
genetics.
NATURE|VOL 431 | 21 OCTOBER 2004 |www.nature.com/nature
See article: http://fire.biol.wwu.edu/trent/trent/Naturedeafdesign.pdf
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Why then
could they
have only
normal
children?
A mutant gibberellin-synthesis gene in rice
New insight into the rice variant that helped to avert famine over thirty years ago.
Nature 416: 701 April 18, 2002
The chronic food shortage that was
feared after the rapid expansion of the
world population in the 1960s was
averted largely by the development of a
high-yielding semi-dwarf variety of rice
known as IR8, the so-called rice ‘green
revolution’. The short stature of IR8 is
due to a mutation in the plant’s sd1 gene,
which encodes an oxidase enzyme
involved in the biosynthesis of
gibberellin, a plant growth hormone.
Gibberellin is also implicated in
green-revolution varieties of wheat, but
the reduced height of those crops is
conferred by defects in the hormone’s
signaling pathway. There are various
reasons for the dwarf phenotype in
plants, but gibberellin (GA) is
one of the most important determinants
of plant height. To investigate whether
the sd1 gene in semi-dwarf rice (Fig. 1a)
could be associated with malfunction of
gibberellin, we tested the response of this
mutant to the hormone. We found that
sd1 seedlings are able to respond to
exogenous gibberellin, which increases
their height to that of wild-type plants
In the early 1970s, a Dr.
Rutger, then in Davis,
Calif., fired gamma
rays at rice. He and his
colleagues found a
semi-dwarf mutant
that gave much higher
yields, partly because it
produced more grain.
Its short size also
meant it fell over less
often, reducing
spoilage. Known as
Calrose 76, it was
released publicly in
1976. Today, Dr.
Rutger said, about half
the rice grown in
California derives from
this dwarf.
Right: wild-type
Left: semi-dwarf (sd1) mutant (more resistant than wild-type to damage
by wind and rain and respond better to certain fertilizers)
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Arabidopsis dwarf mutant
These two plants have the exactly
the same genotype: they are
homozygous for the same recessive,
loss-of-function mutation
The plant on the left has been
treated with an application of
gibberellin. The plant on the right
is untreated.
You have three different (independently isolated) dwarf strains of Arabidopsis:
Mutant Strains 1, 2 & 3
• Each dwarf strain has a recessive, loss-of-function mutation
• Treatment of each mutant strain with gibberellic acid restores normal height
suggesting that they have the same primary defect
• You cross dwarf strain 1 X dwarf strain 3 and the untreated F1 are dwarf
• But when you cross dwarf strain 1 X dwarf strain 2 the untreated F1 are
wild-type in height (non-dwarf)
• How to explain: dwarf X dwarf = wild-type?
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Dwarf plants can result
from a mutation
affecting gibberellin
production as well as
mutations affecting any
step in the cellular
response to this signal
gibberellin biosynthetic pathway
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These mutations show complementation:
Complementation: the production of wild-type F1 progeny when
crossing two parents showing the same recessive mutant phenotype
M1 X M2 
wild-type F1 progeny
(alleles symbols: uppercase = functional allele; lowercase = loss-of-function)
mutant 1: aaBBCC X mutant 2: AAbbCC
ê
F1
AaBbCC wild-type
ê self
What phenotypes will appear in the F2?
Will the progeny ratios be in 1/4’s or 1/16’s or 1/64’s
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Genes are assorting independently
3/4 A- 1/4 aa
3/4 B- 1/4 bb
all CC (not segregating)
9/16
3/16
3/16
1/16
A-B- CC
aaB- CC
A- bb CC
aabbCC
Since a homozygous recessive mutation in either A or B results in the
mutant phenotype
9/16 wild-type 7/16 dwarf = modified Mendelian ratio
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Dwarfism in plants and deafness in humans are examples of
genetic heterogeneity
Genetic (or locus) heterogeneity: Mutations in any one of several genes
may result in identical phenotypes (such as when the genes are required for a
common biochemical pathway or cellular structure)
Heterogeneous trait or genetic heterogeneity: a mutation at any one of a
number of genes can give rise to the same phenotype
Although a single gene difference causes the phenotypic difference between the
dwarf and the wild-type plants, this does not mean that normal height is the
result of the action of a single gene. It means simply that only one gene
differed* between the dwarf and wild-type plants under consideration
* carried alleles with functional differences
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Optional interesting growth-hormone-related genetics
FDA approved genetically modified salmon: addition of Chinook growth
hormone to smaller species
http://opinionator.blogs.nytimes.com/2011/03/17/frankenfish-phobia/?nl=opinion&emc=tya1
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See also optional reading on loss-of-function mutations in
growth hormone receptor in humans: Equadorean villagers
may hold secret to longevity
http://fire.biol.wwu.edu/trent/trent/larondwarfism.pdf
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