Announcement

SAE #1 will take place Wednesday January 24th from

Ø SAE 1
8:35am-9:05am.

Four multiple choice questions, about 15 minutes to

complete, but 30mins are given to promote discussion.

It will be available via the “Quiz” tab at myCourses.

TAs and myself will be present to answer questions.

Don’t have to be physically present at LEA132

the other half hour of the course he is
going to go over concepts that may

f
have been unclear and we are open to
ask questions as well
we are going to discuss genes that have nothing to do with their location on the chromosome
• going to talk about how genes can a ect how other genes are expressed

Interactions between genes in a single pathway:

“one-gene-one-enzyme” hypothesis
• all on one
Gene X pathway but their Gene Y Gene Z
phenotype and
how it is
manifested is
a ected by the
functioning of the
neighbouring
gene

Fig 5.13
 Forward genetic screens to identify genes involved in
a biochemical pathway
• people who have done this
experienment have randomly
mutationed and used a
neurospora (which is a haploid
species)
• you then isolate each spore and
grow each of them seperatly
• then transfer to minimal medium
(minimum metabolize for this
organison to grow )
• won't be able to metabolize in
minial media

Auxotrophy: The inability of an organism to synthesize a particular organic

compound required for its growth
ØIsolation of an arginine auxotrophic mutation

• slowly add back things SEPARATELY • we can see that it can grow in minimal
that may be lacking (ex: vits,, a.a, etc) medium but with amino acids
 • now instead of adding a pool of

ØIsolation of an arginine auxotrophic mutation

amino acids; we add one amino acid
individually
• allows us to determine which a.a
helps it to grow
 • now instead of only providing Ar; they
provide the precursor of the arginine

Interactions between genes in pathways

• since both are able to grow in the
presence of a precursor means the
gene mutated (arg-1) is acting
upstream

Table 5.1

3
naii's ac

• has a mutation that doesn't allow the

conversion of citrulline to arginine
 Genes affecting the same trait
In a forward genetic screen, mutants carrying mutations in different genes
can be isolated (e.g. arg1, arg2, arg3, etc). Also, multiple mutant alleles of
the same genes can be isolated (e.g. different mutant alleles caring
mutations in arg1). Part of the process of studying gene interactions involves
first determining whether the mutations are alleles of the same gene or
different genes. • if you screen enough mutations; you
can start to discover that some
mutations may a ect the same gene

For recessive mutations, we can use the complementation test. • used to determine if it is
acting on the same gene or
• can only be used for recessive mutations
two di erent onces
If two different genes Appear wild type
you start o with purebread
homozygous mutations X
• then you cross in order to
create heterozygous genes
X
with the mutations

a1/a1 X a2/a2
Appear mutant

If two alleles of the SAME GENE

• GIRL WTF IS HE SAYING

Textbookexplains itway
SEEMS SO EASY YET SO Better
DIFFICULT
In a diploid, the complementation test is performed by intercrossing two individuals that are
homozygous for di erent recessive mutations. The next step is to observe whether the progeny have
the wild-type phenotype. If the progeny are wild type, the two recessive mutations must be in
di erent genes because the respective wild-type alleles provide wild-type function. In this case, the
two mutations are said to have complemented. Consider two genes al and a2, named after their
mutant alleles. We can represent the heterozygotes as follows, depending on whether the genes are
on the same chromosome or are on di erent chromosomes

You can see that each locus has one wild-type allele to provide wild-type function, resulting in wild-
type progeny. However, if the progeny are not wild type, then the recessive mutations must be alleles
of the same gene. Because both alleles of the gene are mutants, there is no wild-type allele to
provide wild-type function. These alleles could have di erent mutant sites within the same gene, but
they would both be nonfunctional.
 Interactions
ØHarebell plant between genes in pathways
(harebell plants)

• harebell are naturally blue but Several varieties of true-breeding white flowered
we can nd in the wild some
with white colouring
mutants can be found....are these mutations
of the same or different alleles?
 Complementation testing for harebell plants

Fig 15-15

white $ X blue white $ X blue white £ X blue

all blue all blue all blue

• if all of them give all blue
-Recessive to the blue when crossed with blue they
are recessive
-F1 monohybride cross will tell if the phenotype is caused by one gene or
multiple genes (3:1 ratio of blue to white).
 Complementation testing

• here we are conducting a

monohybrid cross

w$/ w$ w£/w£ w¥/w¥

white $ X white £ white $ X white ¥ white £ X white ¥

all white all blue all blue

Failed to complement complement complement
• means they act on the same
• a ect di erent genes
gene

white $ & white £ have mutations affecting the same gene.

 Genetic basis
ØThe molecular interaction often
of genetic results in a
complementation
modified 9:3:3:1 ratio
• has the wild-type of the
• has wild-type yen
pound

w1£/w1£;; w2+w2+ w1+w1+; w2¥/w2¥ P

w1 w2
• will look like a
wildtype
• because it has at
• create a heterozygous least one copy of
the wild-type gene

w1+/w1£ ; w2+/w2¥ F1

• then you self them

• one wild-type of

9:7 ratio indicates

Blue: 9 w1+ /– +
; w2 /–
9 F each 2

that the two genes in w1+ /– ; w2¥/w2¥ 3 • has only one

White: 7
I
mutation
£ £ +
w1 /w1 ; w2 /– 3
the same pathway
• because if one thing a ects the pathway it a ects the end
result
• even if only one gene is mutated -> it will be white w1£ /w1£ ; w2¥ /w2¥ 1 • both are
mutated
• no longer a 9:3:3:1 ration but 9:7 ratio phenotypically
Three phenotypically identical white harebell mutants
-$, £, and ¥-are intercrossed. Mutations in the same gene (such as
$ and £) cannot complement because the F1 has one gene with two
mutant alleles. The pathway is blocked and the owers are white.
When the mutations are in di erent genes (such as £ and ¥), there is
complementation by the wild-type alleles of each gene in the F1
heterozygote. Pigment is synthesized and the owers are blue.
 Genebetween
ØInteraction a regulatory
interactions protein
and Mendelian and its
ratios:
target
Interaction between regulator gene and target gene
Genotype Phenotype

9
9: r+/- ; a+/-

3: r /r; a+/-

3: r+/- ; a/a 7

1: r /r ; a/a

• in this example expression of "a"

completely depends on transcription Fig 5.18
factor coded by "r"
 cw
Mendelian ratiosynthesized
ØIndependently of two genesand inherited
affecting on thepigments
same
characteristic but working independently.
• this is an example of genes that are acting on the same biological
process but acting on a completely di erent process

Colour of this snake is controlled by two genes:

• the orange gene (O) determines orange pigment

production
• the black gene (B) determines black pigment
production
Camouflage Black
•O + B = Camouflage

Orange Albino
Camouflage O/– ; B/– 9
Black o/o ; B/– 3
Orange O/– ; b/b 3
Albino o/o ; b/b 1
HAS 9 3 3 Ratio
bes genes interact
O and B involved in the same biological process but not in the same pathway!
 Recessive epistasis
Blue-eyed Marry a
• plant where there are
pigments controlling the
I in
Epistasis is a situation where
colour (same as previous
exemple) phenotypic manifestation of
• the di erence is there is an
intermediate here that an allele is dependent on the
actually has a color • how has a 9:3:4 ration
genotype of a different gene.

T L This example is called recessive

epistasis because the recessive
genotype of one gene (w) masks
the pink flower phenotype
associated with the other gene (m)
• epistasis is a term that describes that a mutation on one gene
can a ect the expression of mutation of the other (doesn't
have to be on the same pathway)
w is epistatic to m

• double mutant = gives white owers In this context dihybrid cross result
e
in 9:3:4 ratio where 4 represent
white flower.
Wild-type alleles of two genes (wt and mt) encode enzymes
catalyzing successive steps in the synthesis of a blue petal
Fig 5.19
pigment. Homozygous m/m plants produce magenta owers, and
homozygous w/w plants produce white owers. The double
mutant w/w; m/m also produces white owers, indicating that
white is epistatic to magenta.
 Gene interactions: SUPPRESSORS
snasicamcaeii.info
Suppressor is a mutant allele of a gene that REVERSES the effects of an
ex; there is a protein complex that functions by performing
original mutation. heterodimer phenoty
• if there is a mutation on this gene let's say "m" that
destroys or alters the interaction of the two proteins (can
longer make the heterodimer by changing the a.a
sequences and not allowing them to interect/bind with
one other) the complex will become inactive
• what can happen is there is a second mutation in such a
way that now the new alleles of the S protein can interact
with the modi ed mutant
◦making it functional now

we can see it as these mutations are

suppressors of one another

Fig 5.22
 Gene interactions: modifier
changes the degree of the phenotype
different
Ø Modifier: a second mutation that changes the degree of expression of a mutated
gene (phenotype).
changeslevels of
Ø eg. mutations in the regulatory sequences. transcription

B A
gene a

so here "B" a ects the expression of "A" but

does not completely kill it
• ex: in the absence of "B," only 30% of
gene A is expressed
 Gene interactions: Synthetic lethal
Ø Synthetic lethal: mutations in two genes, each often has a
weak mutant phenotype, resulting in lethality
Ø Eg. Multiproptien complexes
• seen usually in proteins in LARGE
complexes
• let's say you have A and B subunits
◦if you have a mutation on A or B;
then you have partially functioning
large complex (may have weak
phenotype but does still survive)
◦double mutations: A and B ->
becomes lethal / does not survive

Fig 5.23
Modified ratios between genetically
interacting genes Summarizes how genetic interactions between two genes can
a ect the "famous 9;3;3;1 mendelian" ratio
he emphasized these
and expects us to
know their ratios

WON'T ASK ABOUT THIS BECAUSE HE

SAID IT IS TOO COMPLEX