Post on 29-Jan-2016
description
transcript
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
lecture 8. Epistasis and Pathwayslecture 8. Epistasis and Pathways
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Interactions of null allelesInteractions of null alleles
Additivity of nulls implies distinct pathwaysAdditivity of nulls implies distinct pathways
Epistasis of nulls implies common pathway Epistasis of nulls implies common pathway
Additivity of hypomorphs is consistent with anythingAdditivity of hypomorphs is consistent with anything
Synergism of null alleles implies parallel pathways Synergism of null alleles implies parallel pathways with a common targetwith a common target
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
X Y Z1 2 3
Substrate Dependent Pathway
X Y1 2
Z
X Y1 2 3
Z
3Y Z
1 X
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
A B
outcome 1
outcome 2
condition
Switch Regulation Pathway
Yes ON ON outcome 1
outcome 2OFFOFFNo
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
A B
outcome 1
outcome 2
condition
Switch Regulation Pathway
Yes OFF ON outcome 1
outcome 2OFFONNo
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Male tail
Hermaphrodite vulva
spicules
1°
2°
Some C. elegans sexual specializations
1°: the openingvulval muscle-1 insertioncues to male
2°: vulval muscle-2 insertioncues to male
sensory structures that locate the vulvalopening
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
spermathecauterus ovary
oocyteegg
vas deferens
vulvaspiculehook
p.c.s.
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
somatic sex determination in C. elegans
genotype XX XO
+ f mtra-1(lf) m mtra-1(gf) f fher-1(lf) f fher-1(gf) ~m m
f, female somatic tissues; m, male somatic tissues.lf, loss-of-function; gf, gain-of-function
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
somatic sex determination in C. elegans
genotype XX XO
+ f mtra-1(lf) m mtra-1(gf) f fher-1(lf) f fher-1(gf) ~m m
tra-1(lf); her-1(lf) m mtra-1(gf); her-1(gf) f f
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
her-1low X:A tra-1
female
soma
male
soma
her-1(lf)
tra-1(lf)
female
soma
male
soma
OFF
OFF
ON
ON
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
egl-1(sd) + + ced-9(gf)egl-1(sd) + + ced-9(gf)
egl-1(sd) ced-9(gf) + +
egl-1(sd) ced-9(gf+lf) + +
CommonNon-Egl
Rare Egl
mutagen
Intragenic revertant of a dominant
In egl-1(sd) mutants, the HSN dies, and hence the hemaphrodites cannot lay eggs
x
OR
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
"Switch genes"
lf and gf mutations have opposite effectsThe gene controls a binary outcome
gene
A
B
or
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
ced-3(lf) NO cell deathced-4(lf) NO cell deathced-1(lf), 2, etc No engulfmentced-9(gf) NO cell deathced-9(gf+lf) EXTRA cell deathnuc-1 No DNA degradationced-3(lf) ced-9(lf) NO cell deathced-3 (lf) nuc-1(lf) NO cell death
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005
Paul Sternberg CIT 2005Paul Sternberg CIT 2005