Lecture 6: Extensions of Mendelian Genetics, Part 2

Question 1

complementation

Answer 1

occurs when two individuals with mutations in different genes (but causing the same phenotype) are crossed, and their offspring have a normal (wild-type) phenotype.

Question 2

complementation genetics assumes that the mutation is ——

Answer 2

recessive

Question 3

Astyanax mexicanus

Answer 3

• cave fish descended from surface subspecies, but accumulated mutations in genes required for sight, making them blind.

cave 1 x cave 1: F1 blind
cave 1 x cave 2: F1 can see
cave 1 x cave 3: F1 can see

• deficient copies in one lineage were compensated for by the functional copies in the other lineage (complementation)
• this suggested that although the fish in different caves had all converged upon the same outward appearance (blindness), they had taken different evolutionary paths to do this and had acquired mutations in different genes responsible for sight
• this showed that there are many steps to producing an eye, and that different subspecies have mutations in different steps/pathways required for eye development

Question 4

what two possibilities do we have to distinguish between when discussing the effect of mutation on phenotypes?

Answer 4

1. mutations in the SAME gene can give rise to the same phenotype
2. mutations in DIFFERENT genes can also give rise to the same phenotype

Question 5

allelic

Answer 5

alleles of the same gene

Question 6

how does one WT allele and one mutant allele result in a restoration of function?

Answer 6

the wild type allele is haplosufficient so complements the mutant alleles (compensates for what the mutant is lacking) so that the phenotype is wild type.

Question 7

how do we distinguish between complementation and allelism?

Answer 7

• complementation: (WT, M) the wild type allele is haplosufficient so complements the mutant alleles (compensates for what the mutant is lacking) so that the phenotype is wild type.
• allelism (M, M) two mutant alleles cannot complement each other so the phenotype is mutant

Question 8

molecular vs phenotypic visibility of allelism

Answer 8

while the locus appears heterozygous at the molecular level (the two mutant alleles are caused by different base pair substitutions), the individual appears homozygous at the phenotypic level (they express the mutant phenotype to the same degree)

Question 9

history of tomatoes and why they are good genetic models

Answer 9

• domesticated in south and Central America, ~5000 years ago
• brought by the conquistadors to Europe sometime between 1521 and 1544
• pomi d’oro (golden apples) and pomp d’amour (apple of love)
• by 1622, 4 varieties - red, yellow, orange, golden
• by 1700, 7 varieties
• long history of breeding
• good genetic model

Question 10

purpose of testing for allelism

Answer 10

interested in finding genes responsible for a particular trait

Question 11

forward genetics experiment

Answer 11

You observe or induce a mutant phenotype and then work forward to discover which gene(s) caused it (phenotype -> gene)

Question 12

process of testing for allelism or complementation

Answer 12

1. expose a purebred wild type to mutagenesis
2. isolate pure-breeding lines of mutants that express the mutant trait of interest
3. cross the mutants together and observe the phenotypes of the F1, F2, Fn progeny

Question 13

if allelism is the case

Answer 13

• the F1, F2, and Fn progeny will all express the mutant phenotype
• mutant 1 and mutant 2 had the same gene affecting tomato colour

Question 14

if complementation is the case

Answer 14

• the F1 progeny will have the wild type phenotype; they are heterozygous for mutant and wild type alleles
• Mutant 1 and mutant 2 contained different genes affecting the same trait, with mutant 1 containing mutations in one gene and mutant 2 containing mutations in the other

Question 15

complementation testing

Answer 15

• one of the most powerful tests in genetic analysis
• simultaneously a test for allelism (must be one or the other)
• works when the mutant phenotype is recessive
• allows us to uncover how many different genes control a trait

Question 15

draw a flow chart of the two possible outcomes for a complementation/allelism test

Answer 15

wild type -> mutant 1 x mutant 2:

1. F1 progeny: mutant (allelic - mutants uncover 2 alleles at 1 locus)
2. F1 progeny: wild type (complementation - mutants uncover 2 loci controlling the same trait)

Question 16

give two examples of complementation in humans

Answer 16

1. if two non-hearing parents with mutations in DIFFERENT hearing genes have children, complementation will occur and all the F1 progeny will be able to hear (AAbb x aaBB -> AaBb)
2. if two parents with ocular-cutaneous albinism (OCA) with mutations in DIFFERENT determining genes have children then complementation will occur and the children will not have OCA (aaBB x AAbb -> AaBb)

Question 17

when we know that two genes are acting on the same trait, how do we find out whether they are functioning in the same pathway?

Answer 17

1. take two mutant lines, M1 and M2, and cross them together (aaBB x AAbb)
2. create a dihybrid/heterozygous line (AaBb), resulting in a restoration of WT phenotype due to complementation
3. conduct a dihybrid cross (F1xF1)

Question 18

recessive epistasis

Answer 18

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1(aabb)
phenotype ratio: 9 (A_B_): 3 (A_bb): 4 (aaB_ and aabb)

aa is epistatic to B and b - when homozygous, recessive allele of one gene masks both alleles of another gene

Question 19

epistasis

Answer 19

epistasis occurs when one locus masks the effects of another locus acting on the same trait. the locus that is doing the masking is said to be epistatic to the other

Question 20

epistatic ratios allow a geneticist to hypothesise about

Answer 20

the order of genes in a particular pathway; in a biosynthetic or biochemical pathway, the epistatic gene encodes an upstream step

Question 21

upstream step

Answer 21

earlier in the pathway

Question 22

example of recessive epistasis in animals

Answer 22

slide 27

Question 23

example of recessive epistasis in humans

Answer 23

• all type A, type AB, type B, and type O people are H-
• people with hh genotype will appear to be type O regardless of their l locus genotype
• gene for substance H is epistatic to the l gene (hh is epistatic to all combinations of l alleles, except for ii)

Question 24

complementary gene action/reciprocal recessive epistasis

Answer 24

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1 (aabb) phenotype ratio: 9 (A_B_): 7 mutants (A_bb and aaB_ and aabb) aa is epistatic to B and bb is epistatic to A - when homozygous, recessive allele of each gene masks the dominant allele of the other gene

Question 25

example of complementary gene action/ reciprocal recessive epistasis in a plant

Answer 25

slide 31

Question 26

dominant epistasis 1

Answer 26

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1 (aabb) phenotype ratio: 12 (A_B_ and aaB_): 3 (A_bb): 1 (aabb) B is epistatic to A and a. when dominant allele of one gene hides both alleles of the other gene

Question 27

give an example of dominant epistasis 1 in plants

Answer 27

slide 33

Question 28

dominant epistasis 2

Answer 28

genotype ratio: 9 (A_B_): 3 (A_bb): 3 (aaB_): 1 (aabb) phenotype ratio: 13 (A_B_ and aaB_ and aabb): 1(A_bb) B is epistatic to A. when dominant allele of one gene hides effects of dominant allele of other gene.

Question 29

give an example of dominant epistasis 2 in chicken

Answer 29

slide 35

Question 30

do mendelian laws of segregation and independent assortment still apply with gene interactions?

Answer 30

yes.