Fig. 6-1

Chapter 6: from gene to phenotype

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

arg-1+ arg-2+ arg-3+Gene:

Fig. 6-4

“One gene – one enzyme” hypothesis

X Y Z

Fig. 6-5

Human metabolism of phenylalanine and known mutations

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

Fig. 6-8

Recessive mutant allele of a haplosufficient gene

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

Fig. 6-13

Cross of mice heterozygous for the yellow coat color alleleAY/A X AY/A

2 yellow : 1 wild type ratio results from lethality of AY/AY

Fig. 6-14

Manx cat (ML/M)

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 tworecessive genes; if a wild-type phenotype resultsfrom putting both genes in a diploid, we say thatthe 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 recessive phenotype-genes complement -fail to complement-are not alleles -are alleles

a/a+ b/b+ a1/a2

Fig. 6-16

Complementation offlower color mutations

in Campanula

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 theproduct of gene w.

Fig. 6-20

A molecular example of epistasis

Epistasis implies gene interaction

B/-;E/- b/b;E/- B/-;e/e

Coat color in Labrador dogs is controlled by the B gene (black vs. brown pigment) and the E gene (pigment vs. none)

Fig. 6-21

Suppression: a type of epistasis whereby the expression of one gene (the “suppressor” gene) normalizes the phenotype of another gene (the suppressed gene); otherwise, thesuppressor gene produces no apparent phenotype.

Suppression of the purpleoid eye color by a non-allelic suppressor (su)

Fig. 6-22

Model for suppression interactions at the protein level

Penetrance: frequency with which a phenotype is shown by a particular genotype

Expressivity: the degree of phenotypeproduced by a particular genotype

Fig. 6-25

Fig. 6-26

Variable expressivity of the pie-bald phenotype in beagles

Fig. 6-27

Inheritance of a dominant, incompletely penetrant allele

Fig. 6-