Download Evolutionary Engineering

Evolutionary Engineering
Mark D. Rausher
Department of Biology
Duke University
Evolutionary Biology—largely an academic science
• Until recently, few applied applications
• May explain reluctance of many to accept fact of
evolution
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
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
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
resistance management
The Problem:
• Pests evolve counter-resistance to resistant crops,
often within 5-10 years
• Genetically engineered crops cost millions of $$
and take up to a decade to develop
• Genetically engineered crops need an expected lifetime
of more than 10 years to recoup investment
resistance management
The Problem:
• Pests evolve counter-resistance to resistant crops,
often within 5-10 years
• Genetically engineered crops cost millions of $$
and take up to a decade to develop
• Genetically engineered crops need an expected lifetime
of more than 10 years to recoup investment
How can the evolution of counter-resistance be delayed
or prevented?
resistance management
The Solution: Evolutionary Engineering
• Active manipulation of the evolutionary process
for desired outcomes
• Involves manipulation of environment or genetics
of pest population
• Relies on population genetic principles to guide
manipulation
resistance management
The Strategy: HDR
• motivated by desire to develop strategy for delaying
evolution 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 resistant
plants
resistance management
Evolutionary Principles Underlying HDR Strategy
1. Advantageous recessive alleles increase in frequency
much more slowly than dominant or co-dominant alleles
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 trait
RR has different value of trait
R dominant if
RR, Rr have same value of trait
rr has different value of trait
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-resistance
locus:
2
2
p’R = pR (pR WRR + pr WRr )/ (pR WRR + 2pR pr WRr + pr Wrr )
pR , pr = frequencies of counter-resistant and susceptible alleles
Wij = fitness of genotype ij
WRR > Wrr
WRR = 1.0 , Wrr = 0.5
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
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
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
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
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 proportional
to the difference in fitness between genotypes.
resistance management
s = WRR - Wrr
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 proportional
to the difference in fitness between genotypes.
•
•
reduce fitness advantage of resistant homozygote
use Refuges
resistance management
Evolutionary Principles Underlying HDR Strategy
Refuge: plants lacking resistance gene interplanted
among resistant plants.
Resistant Plant
resistance management
Evolutionary Principles Underlying HDR Strategy
Refuge: plants lacking resistance gene interplanted
among resistant plants.
Resistant Plant
Susceptible Plant
resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Genotype
rr
Rr
RR
Insect Fitness
Non-Refuge
0
0
1
resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Genotype
rr
Rr
RR
Insect Fitness
Non-Refuge
Refuge
0
0
1
1
1
1
resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Genotype
rr
Rr
RR
Insect Fitness
Non-Refuge
Refuge
0
0
1
1
1
1
If β is the proportion of plants that are refuge plants, then . . .
resistance management
Evolutionary Principles Underlying HDR Strategy
Refuges reduce fitness difference
Genotype
rr
Rr
RR
Insect Fitness
Non-Refuge
Refuge
0
0
1
1
1
1
Overall
Fitness
β
β
1
resistance management
Simulation of HDR strategy
WRR = 1, Wrr = WRR = 0
β
β
β
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
biological control
Genetic control of pest organisms
• Introduction of low-fitness genotypes into a population
by mass release
• sterile male eradication of screwworm populations
• attempts to suppress sheep blowfly by introducing
lethal alleles
biological control
Genetic control of pest organisms
• Introduction of low-fitness genotypes into a population
by mass release
• sterile male eradication of screwworm populations
• attempts to suppress sheep blowfly by introducing
lethal alleles
• often unsuccessful
• require ability to mass rear organism
• sustained release required—natural selection opposes
biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionary
fixation of lethal or sterile mutants
biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionary
fixation of lethal or sterile mutants
• Meiotic drive (Segregation Distortion)
o
preferential inheritance of one allele over another
in gametes of heterozygotes
Normal Mendelian Segregation
50% of gametes R
Rr
50% of gametes r
biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionary
fixation of lethal or sterile mutants
• Meiotic drive (Segregation Distortion)
o
preferential inheritance of one allele over another
in gametes of heterozygotes
Segregation Distortion
100% of gametes R
Rr
0% of gametes r
biological control
Evolutionary control of pest organisms
• Manipulate evolutionary process to force evolutionary
fixation of lethal or sterile mutants
• Meiotic drive (Segregation Distortion)
o
preferential inheritance of one allele over another
in gametes of heterozygotes
o
driven allele rapidly increases in population
o
link lethality or sterility to driven allele
biological control
Evolutionary control of pest organisms
Normal Chromosome
Driven Chromosome
Drive element
Recessive Female Sterility element
biological control
Evolutionary control of pest organisms
biological control
Evolutionary control of pest organisms
biological control
Evolutionary control of pest organisms
biological control
Evolutionary control of pest organisms
biological control
Evolutionary control of pest organisms
biological control
Evolutionary control of pest organisms
biological control
Evolutionary control of pest organisms
biological control
Evolutionary control of pest organisms
EXTINCTION
biological control
Evolutionary control of pest organisms
EXTINCTION
Will this really work?
biological control
Model Assumptions
• SD is partial to complete
• SD may affect male gametes, female gametes, or
both
• Female homozygotes for driven allele sterile or
inviable
• Female heterozygotes may have reduced fitness
• Male heterozygotes may have reduced fitness
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
˜
˜ ˜ [pp+α(pq+qp)+qq]
˜
˜ ˜
˜
p’ = [pp+γα(pq+qp)]/
˜
˜ ˜ [pp+β
˜ (pq+qp)]
˜ ˜
p˜’ = [pp+δβ
(pq+qp)]/
N ’= [R + βQ] N er(1—N/K)
biological control
Case 1
• Complete male drive
• No drive in females
• Female fertility of heterozygotes = 0.5 — 1
biological control
Case 1
• Complete male drive
• No drive in females
• Female fertility of heterozygotes = 0.5 — 1
Genotype Frequencies
Population Size
1.2
12000
P
1
10000
0.8
7.4, β=1
r r==7.4
8000
Q
0.6
6000
0.4
4000
R
0.2
r = 2.7, β=1
2000
r = 2.7, β=0.5
43
40
37
34
31
28
25
22
19
16
13
10
7
4
1
43
40
37
34
31
28
25
22
19
16
13
10
7
4
0
1
0
biological control
Case 2
• Complete female drive
• No drive in males
• Female fertility of heterozygotes = 0.5 — 1
biological control
Case 2
• Complete female drive
• No drive in males
• Female fertility of heterozygotes = 0.5 — 1
Genotype Frequencies
Population Size
1.2
12000
1
P
10000
R
0.8
8000
Q
29
27
25
23
21
19
17
15
13
11
9
7
5
29
27
25
23
21
19
17
15
13
11
0
9
0
7
2000
5
0.2
3
4000
1
0.4
3
6000
1
0.6
biological control
Conclusions
• By linking a female-sterile or female-fertile mutant
to a meiotic drive agent, pest populations can be
forced to evolve to extinction
• Female-drive likely to be more effective than male drive
• Male drive can be effective if population rate of increase
is high enough
• A single, small release can be effective
biological control
Caveats
• It will be some time before drive elements can be
genetically engineered/manipulated
• Efficacy of strategy needs experimental verification
• Likely to be just one more tool in biological control
arsenal
Evolutionary Engineering
Altering the course of evolution in desirable directions by
manipulating the environment and genetics of
pest organisms has begun and shows promise.