evolutionary engineering mark d. rausher department of biology duke university
TRANSCRIPT
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Evolutionary Engineering
Mark D. Rausher
Department of Biology
Duke University
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Evolutionary Biology—largely an academic science
• Until recently, few applied applications• May explain reluctance of many to accept fact of
evolution
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Evolutionary Biology—largely an academic science
• Until recently, few applied applications• May explain reluctance of many to accept fact of
evolution
Recent applications of evolutionary principles
• disease management• fisheries management• biomolecular engineering• computer design
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Evolutionary Biology—largely an academic science
• Until recently, few applied applications• May explain reluctance of many to accept fact of
evolution
Recent applications of evolutionary principles
• disease management• fisheries management• biomolecular engineering• computer design• resistance management
![Page 5: Evolutionary Engineering Mark D. Rausher Department of Biology Duke University](https://reader035.vdocuments.net/reader035/viewer/2022062713/56649cdc5503460f949a6b14/html5/thumbnails/5.jpg)
Evolutionary Biology—largely an academic science
• Until recently, few applied applications• May explain reluctance of many to accept fact of
evolution
Recent applications of evolutionary principles
• disease management• fisheries management• biomolecular engineering• computer design• resistance management • biological control
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resistance management
The Problem:
• Pests evolve counter-resistance to resistant crops,often within 5-10 years
• Genetically engineered crops cost millions of $$and take up to a decade to develop
• Genetically engineered crops need an expected lifetimeof more than 10 years to recoup investment
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resistance management
The Problem:
• Pests evolve counter-resistance to resistant crops,often within 5-10 years
• Genetically engineered crops cost millions of $$and take up to a decade to develop
• Genetically engineered crops need an expected lifetimeof more than 10 years to recoup investment
How can the evolution of counter-resistance be delayedor prevented?
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resistance management
The Solution: Evolutionary Engineering
• Active manipulation of the evolutionary processfor desired outcomes
• Involves manipulation of environment or geneticsof pest population
• Relies on population genetic principles to guidemanipulation
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resistance management
The Strategy: HDR
• motivated by desire to develop strategy for delayingevolution of counter-resistance by insects to Bt toxins
• pest-management workers, U.S. EPA, large corporations implementing HDR strategy
• engineer crops to produce High Dose of toxin
• intermix Refuges of susceptible plants with resistantplants
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resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
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resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
R recessive if rr, Rr have same value of traitRR has different value of trait
R dominant if RR, Rr have same value of trait rr has different value of trait
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resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
Equation for change in gene frequency at a counter-resistancelocus:
pR = pR (pR WRR + pr WRr )/ (pR WRR + 2pR pr WRr + pr Wrr )22’
pR , pr = frequencies of counter-resistant and susceptible alleles
Wij = fitness of genotype ij
WRR > Wrr
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WRR = 1.0 , Wrr = 0.5
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resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
• make counter-resistance recessive
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resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
• make counter-resistance recessive• use High Dose of toxin
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resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
• make counter-resistance recessive• use High Dose of toxin
![Page 17: Evolutionary Engineering Mark D. Rausher Department of Biology Duke University](https://reader035.vdocuments.net/reader035/viewer/2022062713/56649cdc5503460f949a6b14/html5/thumbnails/17.jpg)
resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
• make counter-resistance recessive• use High Dose of toxin
![Page 18: Evolutionary Engineering Mark D. Rausher Department of Biology Duke University](https://reader035.vdocuments.net/reader035/viewer/2022062713/56649cdc5503460f949a6b14/html5/thumbnails/18.jpg)
resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
• make counter-resistance recessive• use High Dose of toxin
2. Rate of increase of advantageous allele is proportionalto the difference in fitness between genotypes.
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resistance management
s = WRR - Wrr
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resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency much more slowly than dominant or co-dominant alleles
• make counter-resistance recessive• use High Dose of toxin
2. Rate of increase of advantageous allele is proportionalto the difference in fitness between genotypes.
• reduce fitness advantage of resistant homozygote• use Refuges
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resistance management
Evolutionary Principles Underlying HDR Strategy
Refuge: plants lacking resistance gene interplantedamong resistant plants.
Resistant Plant
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resistance management
Evolutionary Principles Underlying HDR Strategy
Refuge: plants lacking resistance gene interplantedamong resistant plants.
Resistant Plant Susceptible Plant
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resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Insect FitnessGenotype Non-Refuge
rr 0 Rr 0 RR 1
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resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Insect FitnessGenotype Non-Refuge Refuge
rr 0 1 Rr 0 1 RR 1 1
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resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Insect FitnessGenotype Non-Refuge Refuge
rr 0 1 Rr 0 1 RR 1 1
If β is the proportion of plants that are refuge plants, then . . .
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resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Insect Fitness OverallGenotype Non-Refuge Refuge Fitness
rr 0 1 β Rr 0 1 β RR 1 1 1
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resistance management
Simulation of HDR strategy WRR = 1, Wrr = WRR = 0
ββ β
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resistance management
Conclusions:
1. HDR Strategy can delay evolution of counter-resistance
2. Refuges constituting 10-20% or more of plants are needed to delay evolution of counter-resistance for substantial periods
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biological control
Genetic control of pest organisms
• Introduction of low-fitness genotypes into a populationby mass release
• sterile male eradication of screwworm populations
• attempts to suppress sheep blowfly by introducinglethal alleles
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biological control
Genetic control of pest organisms
• Introduction of low-fitness genotypes into a populationby mass release
• sterile male eradication of screwworm populations
• attempts to suppress sheep blowfly by introducinglethal alleles
• often unsuccessful
• require ability to mass rear organism
• sustained release required—natural selection opposes
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biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionaryfixation of lethal or sterile mutants
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biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionaryfixation of lethal or sterile mutants
• Meiotic drive (Segregation Distortion)
o preferential inheritance of one allele over anotherin gametes of heterozygotes
Normal Mendelian Segregation
50% of gametes RRr
50% of gametes r
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biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionaryfixation of lethal or sterile mutants
• Meiotic drive (Segregation Distortion)
o preferential inheritance of one allele over anotherin gametes of heterozygotes
Segregation Distortion
100% of gametes RRr
0% of gametes r
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biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionaryfixation of lethal or sterile mutants
• Meiotic drive (Segregation Distortion)
o preferential inheritance of one allele over anotherin gametes of heterozygotes
o driven allele rapidly increases in population
o link lethality or sterility to driven allele
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biological control
Evolutionary control of pest organisms
Normal Chromosome
Driven Chromosome
Recessive Female Sterility elementDrive element
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biological control
Evolutionary control of pest organisms
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biological control
Evolutionary control of pest organisms
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biological control
Evolutionary control of pest organisms
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biological control
Evolutionary control of pest organisms
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biological control
Evolutionary control of pest organisms
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biological control
Evolutionary control of pest organisms
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biological control
Evolutionary control of pest organisms
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biological control
Evolutionary control of pest organisms
EXTINCTION
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biological control
Evolutionary control of pest organisms
EXTINCTION
Will this really work?
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biological control
Model Assumptions
• SD is partial to complete
• SD may affect male gametes, female gametes, orboth
• Female homozygotes for driven allele sterile orinviable
• Female heterozygotes may have reduced fitness
• Male heterozygotes may have reduced fitness
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biological control
Model Equations
Male gamete freq.: p = (P+γαQ)/(P+αQ+R)
Female gamete freq: p = (P+δβQ)/(P+βQ)
P, Q, R are genotype frequencies
p = [pp+γα(pq+qp)]/ [pp+α(pq+qp)+qq]
p = [pp+δβ (pq+qp)]/ [pp+β (pq+qp)]
N = [R + βQ] N er(1—N/K)
˜
’ ˜
’˜ ˜
˜ ˜ ˜ ˜ ˜ ˜
˜ ˜ ˜ ˜ ˜
’
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biological control
Case 1
• Complete male drive • No drive in females• Female fertility of heterozygotes = 0.5 — 1
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biological control
Case 1
• Complete male drive• No drive in females• Female fertility of heterozygotes = 0.5 — 1
0
0.2
0.4
0.6
0.8
1
1.2
1 4 7
10
13
16
19
22
25
28
31
34
37
40
43
Genotype Frequencies Population Size
P
Q
R
r = 7.4
0
2000
4000
6000
8000
10000
12000
1 4 7
10
13
16
19
22
25
28
31
34
37
40
43
r = 7.4, β=1
r = 2.7, β=1
r = 2.7, β=0.5
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biological control
Case 2
• Complete female drive• No drive in males• Female fertility of heterozygotes = 0.5 — 1
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biological control
Case 2
• Complete female drive• No drive in males• Female fertility of heterozygotes = 0.5 — 1
Genotype Frequencies Population Size
0
0.2
0.4
0.6
0.8
1
1.2
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29
0
2000
4000
6000
8000
10000
12000
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29
P
Q
R
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biological control
Conclusions
• By linking a female-sterile or female-fertile mutantto a meiotic drive agent, pest populations can beforced to evolve to extinction
• Female-drive likely to be more effective than male drive
• Male drive can be effective if population rate of increaseis high enough
• A single, small release can be effective
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biological control
Caveats
• It will be some time before drive elements can begenetically engineered/manipulated
• Efficacy of strategy needs experimental verification
• Likely to be just one more tool in biological controlarsenal
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Evolutionary Engineering
Altering the course of evolution in desirable directions bymanipulating the environment and genetics ofpest organisms has begun and shows promise.