1. Fig. 6-1 Chapter 6: from gene to phenotype

2. 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

3. Fig. 6-4

4. arg-1 + arg-2 + arg-3 + Gene: Fig. 6-4 “One gene – one enzyme” hypothesis XYZ

5. Fig. 6-5 Human metabolism of phenylalanine and known mutations

6. Known mutations in the human phenylalanine hydroxylase gene Fig. 6-6

7. 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)

8. Fig. 6-7

9. Fig. 6-8 Recessive mutant allele of a haplosufficient gene

10. Inter-allelic interactions Incomplete dominance heterozygote phenotype is intermediate F2 phenotypic ratio 1:2:1 Co-dominance both alleles produce a phenotype

11. Example of co-dominance: ABO blood group GroupGenotype AI A / I A or I A / i BI B / I B or I B / i Oi / i ABI A / I B I A, I B, and i are multiple alleles of the I gene

12. Inter-allelic interactions Incomplete dominance heterozygote phenotype is intermediate F2 phenotypic ratio 1:2:1 Co-dominance both alleles produce a phenotype Lethal alleles

13. Fig. 6-13 Cross of mice heterozygous for the yellow coat color allele A Y /A X A Y /A 2 yellow : 1 wild type ratio results from lethality of A Y /A Y

14. Fig. 6-14 Manx cat (M L /M)

15. 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

16. 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 phenotyperecessive phenotype -genes complement-fail to complement -are not alleles-are alleles a/a + b/b + a 1 /a 2

17. Fig. 6-16 Complementation of flower color mutations in Campanula

18. Complementation tests can be performed heterokaryons in Neurospora Fig. 6-17

19. 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”)

20. 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.

21. Fig. 6-20 A molecular example of epistasis Epistasis implies gene interaction

22. 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

23. 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.

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

25. Fig. 6-22 Model for suppression interactions at the protein level

26. Penetrance: frequency with which a phenotype is shown by a particular genotype Expressivity: the degree of phenotype produced by a particular genotype

27. Fig. 6-25

28. Fig. 6-26 Variable expressivity of the pie-bald phenotype in beagles

29. Fig. 6-27 Inheritance of a dominant, incompletely penetrant allele

30. Fig. 6-