Epistasis - California State Polytechnic University, Pomonacwlamunyon/BIO421/BIO421Lec3.pdfMutant...

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Transcript of Epistasis - California State Polytechnic University, Pomonacwlamunyon/BIO421/BIO421Lec3.pdfMutant...

Epistasis

Primary spermatocyte

Secondary spermatocytes

Residual body

Spermatid

Spiky intermediate

Pseudopod formation

Spermatozoon

Spermiogenesis

fertilization

Mutation analysis

spe-46 spe-47

spe-46 spe-47

spe-6

spe-26, spe-4, spe-5

fer-2, fer-6

fer-3, fer-4 fer-15

spe-8, spe-12, spe-19, spe-27, spe-29

fer-1, spe-10, spe-17

fer-14, spe-9, spe-13, spe-16

spe-11

spe-44

spe-27 mutant

sterile

unfertilized oocytes

spe-27 Suppressor Screen mutate spe-27 mutant

+ Unknown mutation “suppressors”

FERTILE fertilized eggs

Characteristic Properties of Amino Acids

Mutant Name Allele Gene 1-11 hc163 spe-6 2-6 hc164 spe-6 2-2 hc165 spe-6 1-4 hc166 spe-6 2-37 hc167 spe-6 2-38 hc168 spe-6 1-10 hc169 spe-6 2-1 hc170 spe-6 2-21 hc171 spe-6 2-4 hc172 spe-6 1-7 hc173 spe-6 2-30 hc174 spe-6 1-1 hc175 spe-6 2-28 hc176 spe-6 2-39 hc177 spe-6 2-19 hc186 spe-6 2-14 hc187 spe-6 2-5 hc188 spe-6 2-3 hc189 spe-6 2-29 hc190 spe-6 2-7 zq11 spe-6 2-15 hc203 spe-6 2-20 hc196 spe-4 1-8 hc197 spe-46 2-36 hc198 spe-47 2-42 hc201 2-22 hc202 1-12 hc204 1-5 hc205 2-11 2-23 zq10 2-40 1-14 zq9 1-17 zq7 2-10 zq12 1-6 1-3 hc195 2-18 hc200 1-18 zq6 2-41 hc199 2-43 1-15 1-2 zq8

Complementation tests show all these mutations (alleles) affected the same gene, spe-6

mutants recovered from a screen for spermatogenesis defects

Complementation tests not yet completed

Complementation tests showed these mutations affect unique, unknown genes

SPE-8 protein

Allele specific (interaction) suppressor

Chaperone type high copy number suppressor

A

B

C

B

D Activity (gene expression, exocytosis, etc.)

*

We conduct a suppressor screen to recover mutations that suppress a mutation that affects protein B. A mutation that knocks out protein D would act as a bypass supressor by allowing the activity to occur. However, there would be no regulation of the activity through the pathway.

In this hypothetical signaling pathway, protein D prevents some activity. When the pathway is activated and the signal is transduced through proteins A, B, and C, the effect is to inhibit protein D, allowing the activity to proceed. A mutation in protein B would prevent the activity from ever occurring.

Bypass type suppressor

Mutant Name Allele Gene 1-11 hc163 spe-6 2-6 hc164 spe-6 2-2 hc165 spe-6 1-4 hc166 spe-6 2-37 hc167 spe-6 2-38 hc168 spe-6 1-10 hc169 spe-6 2-1 hc170 spe-6 2-21 hc171 spe-6 2-4 hc172 spe-6 1-7 hc173 spe-6 2-30 hc174 spe-6 1-1 hc175 spe-6 2-28 hc176 spe-6 2-39 hc177 spe-6 2-19 hc186 spe-6 2-14 hc187 spe-6 2-5 hc188 spe-6 2-3 hc189 spe-6 2-29 hc190 spe-6 2-7 zq11 spe-6 2-15 hc203 spe-6 2-20 hc196 spe-4 1-8 hc197 spe-46 2-36 hc198 spe-47 2-42 hc201 2-22 hc202 1-12 hc204 1-5 hc205 2-11 2-23 zq10 2-40 1-14 zq9 1-17 zq7 2-10 zq12 1-6 1-3 hc195 2-18 hc200 1-18 zq6 2-41 hc199 2-43 1-15 1-2 zq8

Complementation tests show all these mutations (alleles) affected the same gene, spe-6

mutants recovered from a screen for spermatogenesis defects

Complementation tests not yet completed

Complementation tests showed these mutations affect unique, unknown genes

From Morgan and Bridges 1916, p20

From W.E. Castle 1919. Is the arrangement of the genes in the chromosome linear? PNAS 5:25-32

Castle’s chromosomal arrangement