LECTURE 10: FROM GENE TO PHENOTYPE I Fexam 1: review Fchapter 6 Fquestions & concepts Fgenes & gene products Fallele interactions Fgene & protein interactions.

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

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)

precursor ornithine citrulline arginine

enzyme X enzyme Y enzyme Z

GENES & GENE PRODUCTS

results arginine metabolism biochemical pathway

arg-1+ arg-2+ arg-3+

precursor ornithine citrulline arginine

enzyme X enzyme Y enzyme Z

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

P

F1

F2

red x white

red x red

¾ red + ¼ white3 : 1

dominant & recessive alleles...

DOMINANT & RECESSIVE ALLELES

P

F1

F2

red x white

pink x pink

¼ red + ½ pink + ¼ white1 : 2 : 1

incomplete dominance (= semidominance)...

INCOMPLETELY DOMINANT ALLELES

phenotypes are quantitatively different

are pink flowers more red or more white?

INCOMPLETELY DOMINANT ALLELES

why is this not blending?

ABO blood type i recessive to both dominant alleles (IA & IB > i)

GENOTYPE PHENOTYPE ANTIGENS ANTIBODIES RECEIVE FROM DONATE TO IAIA

IAi A A anti-B A & O A & AB

IBIB

IBi B B anti-A B & O B & AB

IAIB AB AB none all AB ii O none anti-A & -B O all

CODOMINANT ALLELES

IAIB is AB, qualitatively different from A or B

ABO blood type 6 possible genotypes & 4 possible phenotypes

GENOTYPE PHENOTYPE ANTIGENS ANTIBODIES RECEIVE FROM DONATE TO IAIA

IAi A A anti-B A & O A & AB

IBIB

IBi B B anti-A B & O B & AB

IAIB AB AB none all AB ii O none anti-A & -B O all

MULTIPLE ALLELES

influences variation of trait in populations

CONDITIONAL ALLELES influenced by environment, e.g.:

temperature (hot or cold) desiccation nutrient requirement chemicals infection

P

F1

F2

shi+ x shits

shi+/shits x shi+/shits

all active @ 25º

1

e.g.: temperature sensitive shibire (paralyzed) mutant

CONDITIONAL ALLELES

shits wild type @ 25º = permissive temperature

P

F1

F2

shi+ x shits

shi+/shits x shi+/shits

¾ active + ¼ paralyzed @ 29º

3 : 1

e.g.: temperature sensitive shibire (paralyzed) mutant

CONDITIONAL ALLELES

shits paralyzed @ 29º = restrictive temperature

LETHAL ALLELES homozygotes lethal (can be dominant or recessive)

e.g., yellow (AY) allele in mice

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

AY/AY AY/A

AY/A A/A

P

F1

don’t see these

2/3 AY/A yellow + 1/3 A/A black

Cy–/Cy– Cy–/Cy+

Cy–/Cy+ Cy+/Cy+

P

F1

Cy– Cy–

Cy+ Cy+

¾ alive + ¼ dead

3 : 1

e.g.: Curly (Cy) mutations in Drosophila

LETHAL ALLELES

—— x ——

2/3 curly + 1/3 wild type

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 fruitlessfru/fru fruitless x fru+/fru+ wild type

do not mate, no progeny

P

F1

F2

P

F1

mbmB– mbmB–

mbmB+ mbmB+

¾ alive + ¼ sterile

3 : 1

e.g.: mushroom body miniature B (mbmB) mutations

STERILE ALLELES

mbmB+

mbmB–

———— x ————

homozygous mbmB– live but give no offspring