LECTURE 10: FROM GENE TO PHENOTYPE I exam 1: review chapter 6 questions & concepts genes & gene products allele interactions gene & protein interactions chi-square applications

CHAPTER 6: QUESTIONS how do genes influence the organism? what are gene products? ... & what are they doing? do alleles determine a specific phenotype? how do genes interact? can we dissect gene interactions using mutations?

CHAPTER 6: CONCEPTS if 2 haploid genomes (i.e., the gametes of diploids) each with 1 recessive mutation are combined  mutant phenotype?... the mutations are allelic (they identify alleles of the same gene) or  wild type phenotype?... the mutations are not allelic (they identify alleles of different genes)

CHAPTER 6: CONCEPTS dominance can be complete or incomplete some mutations can cause lethality or sterility expression of some mutations can be dependent on environment  conditional mutations most traits are determined by sets of genes that interact with the environment modified monohybrid ratios reveal allele interactions modified dihybrid ratios reveal gene interactions

GENE INTERACTION genes never do anything by themselves levels of interaction between alleles of 1. the same gene 2. different genes

GENE INTERACTION 3 ways to study these interactions 1. genetic analysis (ch 6) 2. functional genomics (ch 12) 3. proteomics (ch 12)

GENES & GENE PRODUCTS 1st clue from human “inborn metabolism error” PKU (phenylketonuria) autosomal recessive phenylalanine  tyrosine  phenylpyruvic acid (toxic)

GENES & GENE PRODUCTS “1 gene - 1 enzyme” hypothesis Beadle & Tatum (1940s, Nobel Prize) Neurospora crassa (haploid fungus) mutants (by irradiation) & analysis

supports growth of all genotypes GENES & GENE PRODUCTS supports growth of all genotypes

GENES & GENE PRODUCTS

GENES & GENE PRODUCTS

GENES & GENE PRODUCTS 3 arginine auxotrophs (arginine metabolism mutants) mapped to different loci... different genes growth on medium supplemented with different related compounds

GENES & GENE PRODUCTS chemical structure  biochemical pathway (B & T) enzyme X enzyme Y enzyme Z    precursor  ornithine  citrulline  arginine

GENES & GENE PRODUCTS results  arginine metabolism biochemical pathway arg-1+ arg-2+ arg-3+    enzyme X enzyme Y enzyme Z    precursor  ornithine  citrulline  arginine

DNA  mRNA  polypeptide GENES & GENE PRODUCTS results  “1 gene - 1 enzyme” hypothesis more accurately “1 gene - 1 polypeptide” most genes encode physical structure of proteins DNA  mRNA  polypeptide some genes encode functional RNA only, e.g. tRNA rRNA

GENES & GENE PRODUCTS

GENES & GENE PRODUCTS

ALLELE INTERACTION interactions between alleles of one gene 1. dominance / recessiveness 2. semi-dominance = incomplete dominance 3. co-dominance (e.g.: IA & IB of ABO system) 4. multiple alleles (e.g.: IA, IB & i of ABO system) 5. conditional (e.g.: temperature sensitive) 6. lethality 7. sterility

DOMINANT & RECESSIVE ALLELES mutation recessive  + allele haplosufficient mutation dominant  + allele haploinsufficient

DOMINANT & RECESSIVE ALLELES P F1 F2 red x white  red x red ¾ red + ¼ white 3 : 1

INCOMPLETELY DOMINANT ALLELES incomplete dominance (= semidominance)... P F1 F2 red x white  pink x pink ¼ red + ½ pink + ¼ white 1 : 2 : 1 phenotypes are quantitatively different

INCOMPLETELY DOMINANT ALLELES are pink flowers more red or more white? why is this not blending?

CODOMINANT ALLELES ABO blood type i recessive to both dominant alleles (IA & IB > i) IAIB is AB, qualitatively different from A or B

MULTIPLE ALLELES ABO blood type 6 possible genotypes & 4 possible phenotypes influences variation of trait in populations

CONDITIONAL ALLELES influenced by environment, e.g.: temperature (hot or cold) desiccation nutrient requirement chemicals infection

shi+/shits x shi+/shits CONDITIONAL ALLELES e.g.: temperature sensitive shibire (paralyzed) mutant P F1 F2 shi+ x shits  shi+/shits x shi+/shits all active @ 25º 1 shits wild type @  25º = permissive temperature

CONDITIONAL ALLELES e.g.: temperature sensitive shibire (paralyzed) mutant P F1 F2 shi+ x shits  shi+/shits x shi+/shits ¾ active + ¼ paralyzed @ 29º 3 : 1 shits paralyzed @  29º = restrictive temperature

LETHAL ALLELES homozygotes lethal (can be dominant or recessive) e.g., yellow (AY) allele in mice

¼ AY/AY lethal + ½ AY/A yellow + ¼ A/A black LETHAL ALLELES homozygotes lethal (can be dominant or recessive) e.g., yellow (AY) dominant allele in mice AY/A  x AY/A   ¼ AY/AY lethal + ½ AY/A yellow + ¼ A/A black P F1 don’t see these AY/AY AY/A A/A 2/3 AY/A yellow + 1/3 A/A black

LETHAL ALLELES e.g.: Curly (Cy) mutations in Drosophila Cy– Cy–  ¾ alive + ¼ dead 3 : 1 —— x —— P F1 2/3 curly + 1/3 wild type Cy–/Cy– Cy–/Cy+ Cy+/Cy+

STERILE ALLELES homozygotes sterile (can be dominant or recessive) e.g., fruitless (fru) allele in Drosophila

STERILE ALLELES homozygotes sterile (can be dominant or recessive) e.g., fruitless (fru) allele in Drosophila fru+/fru  x fru+/fru   ¾ wild type + ¼ fruitless fru/fru fruitless  x fru+/fru+ wild type   do not mate, no progeny P F1 F2

STERILE ALLELES e.g.: mushroom body miniature B (mbmB) mutations mbmB– mbmB– mbmB+ mbmB+  ¾ alive + ¼ sterile 3 : 1 mbmB+ mbmB– ———— x ———— P F1 homozygous mbmB– live but give no offspring