Why?
1. Constraint
2. Mutation accumulation (Medawar, 1946)
3. Antagonistic pleiotropy (Medawar, 1946; Williams, 1957)
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Charlesworth (2000) Genetics 156: 927-931.
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceConstraint: ‘wear and tear’
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
Birds in zoo
Ricklefs (1998) Am. Nat. 152: 24-44.
Constraint
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceMutation accumulation
So after 1 month 10 break
10% breakage/month
100 tubes
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
10% breakage/month
+ 1/9 fecundity per unbroken individual
… so population number is stable
So after 1 month 10 break
100 tubes
100 tubes
Mutation accumulation
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceMutation accumulation
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
= ‘brittle’ mutation has 20% breakage rate
So after 1 month:9/90 ‘regular’ break2/10 ‘brittle’ break
Differential breakage rate
100 tubes
Mutation accumulation
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
= ‘brittle’ mutation has 20% breakage rate
So after 1 month:9/90 ‘regular’ break2/10 ‘brittle’ break
Differential breakage rate
fecundity replaces broken individuals100 tubes
100 tubes
Mutation accumulation
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
Early expression of ‘brittle’
Late expression of ‘brittle’
Mutation accumulation
The evolution of senescence
Theory:ConstraintMutation accumulationAntagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
Early expression of ‘brittle’
Late expression of ‘brittle’
Mutation accumulation
The evolution of senescence
Theory:ConstraintMutation accumulationAntagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEarly expression of ‘brittle’
Late expression of ‘brittle’
Mutation accumulation
The evolution of senescence
Theory:ConstraintMutation accumulationAntagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceAntagonistic pleiotropy
Pemberton et al. (1991) Evolution 45: 93-103.Hedrick (1999) Heredity 82: 126-133.
A gene influences two traits simultaneously: selection for one trait is counteracted by selection against another:
genotypes that were associated with enhanced juvenile survival tended to reduce adult reproductive success.
4
4.2
4.4
4.6
ss fs/ff
Genotype
Age
at f
irst c
alvi
ng
00.20.40.60.8
ss fs ff
Juve
nile s
urviv
al
0.4
0.5
0.6
0.7
ss fs/ffMpi Genotype
Fecu
ndity
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
Positively effects fitnessearly in life
Antagonistic pleiotropy
Negatively effects fitnesslate in life
Gene ‘A’
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
Positively effects fitnessearly in life
Antagonistic pleiotropy
Negatively effects fitnesslate in life
Gene ‘A’
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Mutation accumulation
Selection is ineffective at removing mutations with effects in old age.
Antagonistic pleiotropy
Early reproduction is favoured by natural selection.
Mutation with positive effect on fitness when young can increase even if it
has negative effects late in life:
“necessary cost of processes beneficial to youth”
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Partridge & Barton (1993) Nature 362: 305-311.
Mutation accummulation & antagonistic pleiotropy:
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
•Senescence greatest when extrinsic
mortality is high because: few individuals
survive that long, therefore, there will be
little selection against deleterious mutations
in old age.
•Why invest in repair if you’re going to die
for other reasons first?
Extrinsic mortality rate
Rat
e of
sen
esce
nce
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Partridge & Barton (1993) Nature 362: 305-311.
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: comparative tests
Birds in zoo
Ricklefs (1998) Am. Nat. 152: 24-44.
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Mutation accummulation & Antagonistic pleiotropy:
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Senescence
•Senescence greatest when extrinsic
mortality is high because: few individuals
survive that long, therefore, there will be
little selection against deleterious mutations
in old age.
•Why invest in repair if you’re going to die
for other reasons first?
Extrinsic mortality rate
Rat
e of
sen
esce
nce
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Partridge & Barton (1993) Nature 362: 305-311.
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: comparative tests
Ricklefs (1998) Am. Nat. 152: 24-44.
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: selection experiments
Service et al. (1988) Evolution 42: 708-716.
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: selection experiments
Service et al. (1988) Evolution 42: 708-716.
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: selection experiments
Service et al. (1988) Evolution 42: 708-716.
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: selection experiments
Service et al. (1988) Evolution 42: 708-716.
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: selection experiments
Service et al. (1988) Evolution 42: 708-716.
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
1. Select for high late-life fitness2. Select for high early-life fecundity
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: selection experiments
Service et al. (1988) Evolution 42: 708-716.
No change
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceEmpirical evidence: aging genes
Hekimi & Guarente (2003) Science 299: 1351-1354.
Nematode Caenorhabditis elegans
Reduces ROS production outside the mitochondria
Detoxifies ROS in the mitochondria
Reduces ROS production in the mitochondria
The evolution of senescence
Theory:ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
The evolution of senescenceTheory:
ConstraintMutation accumulation Antagonistic pleiotropy
Empirical evidence:Comparative testsSelection experimentsAging genes
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
Overview
Biol 418: Evolutionary EcologyLife History Evolution
Jennifer Gow
SenescenceReferences
Charlesworth (2000) Genetics 156: 927-931.
Hedrick (1999) Heredity 82: 126-133.
Hekimi & Guarente (2003) Science 299: 1351-1354.
Partridge & Barton (1993) Nature 362: 305-311.
Pemberton et al. (1991) Evolution 45: 93-103.
Ricklefs (1998) Am. Nat. 152: 24-44.
Service et al. (1988) Evolution 42: 708-716.