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Chapter 6: from gene to phenotype
Fig. 6-1
Using Neurospora, Beadle & Tatum showed
that genes encode enzymes and that most
enzymes work in biochemical pathways
• Wild-type grows on minimal medium (prototrophic)
(has genes/enzymes to biosynthesize virtually all
compounds required for life)
• Isolated mutants that require specific nutrient in
medium (auxotrophic; defective in a pathway)
• Analyzed mutants to identify steps (enzymes) in
the pathway
Fig. 6-4
Fig. 6-4
Gene:
arg-1+
arg-2+
X
arg-3+
Y
Z
“One gene – one enzyme” hypothesis
Human metabolism
of phenylalanine
and known mutations
Fig. 6-5
Known mutations in the
human phenylalanine
hydroxylase gene
Fig. 6-6
Consequences of mutations on protein function
Recessive mutations
• Partially reduce protein function (“leaky” mutations)
• Abolish protein function (“null” mutations)
(will be recessive if one wild-type gene copy if
sufficient to support normal cell function)
Dominant mutations
• Haplo-insufficient mutations (one wild-type gene copy is
insufficient)
• Gain-of-function mutations (novel function of protein or
mis-expression of gene)
Mutations with no effect on protein function
(“silent” mutations)
Fig. 6-7
Recessive mutant allele of a haplosufficient gene
Fig. 6-8
Inter-allelic interactions
Incomplete dominance
• heterozygote phenotype is intermediate
• F2 phenotypic ratio 1:2:1
Co-dominance
• both alleles produce a phenotype
Example of co-dominance: ABO blood group
Group
Genotype
A
IA / IA
or
IA / i
B
IB / IB
or
IB / i
O
i / i
AB
IA / IB
IA , IB , and i are multiple alleles of the I gene
Inter-allelic interactions
Incomplete dominance
• heterozygote phenotype is intermediate
• F2 phenotypic ratio 1:2:1
Co-dominance
•both alleles produce a phenotype
Lethal alleles
Cross of mice heterozygous for the yellow coat color allele
AY/A X AY/A
2 yellow : 1 wild type ratio results from lethality of AY/AY
Fig. 6-13
Manx cat (ML/M)
Fig. 6-14
pleiotropism: single gene difference can affect
multiple phenotypes
Example: Drosophila white mutation
• lack of pigment in eye, testis sheath, Malphighian
tubules
• electroretinogram defects
• impaired vision, resulting in behavioral deviation
• change in primary structure of the white protein
complementation: a test for the allelism of two
recessive genes; if a wild-type phenotype results
from putting both genes in a diploid, we say that
the genes complement each other (i.e., they are
alleles of different genes)
Test:
cross individuals carrying the unknown genes,
and observe the phenotype of the hybrid
“a/a” X “a/a”
normal phenotype
-genes complement
-are not alleles
a/a+
b/b+
recessive phenotype
-fail to complement
-are alleles
a1/a2
Complementation of
flower color mutations
in Campanula
Fig. 6-16
Complementation tests can be performed
heterokaryons in Neurospora
Fig. 6-17
w/w; m/m double mutant: is white flower
- indistinguishable from w/w; m/+ mutant
- gene m mutation is not apparent in the double
mutant (is “masked”)
w/w; m/m double mutant: is white flower
- indistinguishable from w/w; m/+ mutant
- gene m mutation is not apparent in the double
mutant (is “masked”)
Epistasis: the expression of one gene is not
observed in the presence of another,
non-allelic gene
Gene w mutations are epistatic to gene m
mutations; the product of gene m is apparently
“downstream” in a pathway that includes the
product of gene w.
A molecular example of epistasis
Epistasis implies
gene interaction
Fig. 6-20
Coat color in Labrador dogs is controlled by the
B gene (black vs. brown pigment) and the
E gene (pigment vs. none)
B/-;E/-
Fig. 6-21
b/b;E/-
B/-;e/e
Suppression:
a type of epistasis whereby
the expression of one gene (the “suppressor”
gene) normalizes the phenotype of another
gene (the suppressed gene); otherwise, the
suppressor gene produces no apparent
phenotype.
Suppression of the purpleoid eye color by a non-allelic suppressor (su)
Model for suppression interactions at the protein level
Fig. 6-22
Penetrance: frequency with which a
phenotype is shown by a particular genotype
Expressivity: the degree of phenotype
produced by a particular genotype
Fig. 6-25
Variable expressivity of the
pie-bald phenotype
in beagles
Fig. 6-26
Inheritance of a dominant, incompletely penetrant allele
Fig. 6-27
Fig. 6-