Evolutionary Engineering Mark D. Rausher Department of Biology Duke University.

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



evolution

Recent applications of evolutionary principles

• disease management• fisheries management• biomolecular engineering• computer design



evolution


• disease management• fisheries management• biomolecular engineering• computer design• resistance management



evolution


• 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 lifetimeof more than 10 years to recoup investment


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?


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


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


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




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

WRR = 1.0 , Wrr = 0.5




• make counter-resistance recessive




• make counter-resistance recessive• use High Dose of toxin





2. Rate of increase of advantageous allele is proportionalto the difference in fitness between genotypes.


s = WRR - Wrr





2. Rate of increase of advantageous allele is proportionalto the difference in fitness between genotypes.

• reduce fitness advantage of resistant homozygote• use Refuges



Refuge: plants lacking resistance gene interplantedamong resistant plants.

Resistant Plant



Refuge: plants lacking resistance gene interplantedamong resistant plants.

Resistant Plant Susceptible Plant



Refuges reduce fitness difference

Insect FitnessGenotype Non-Refuge

rr 0 Rr 0 RR 1




Insect FitnessGenotype Non-Refuge Refuge

rr 0 1 Rr 0 1 RR 1 1




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 . . .




Insect Fitness OverallGenotype Non-Refuge Refuge Fitness

rr 0 1 β Rr 0 1 β RR 1 1 1


Simulation of HDR strategy WRR = 1, Wrr = WRR = 0

ββ β


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 populationby mass release

• sterile male eradication of screwworm populations

• attempts to suppress sheep blowfly by introducinglethal alleles

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

biological control

Evolutionary control of pest organisms

• Manipulate evolutionary process to force evolutionaryfixation of lethal or sterile mutants

biological control



• 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

biological control





Segregation Distortion

100% of gametes RRr

0% of gametes r

biological control





o driven allele rapidly increases in population

o link lethality or sterility to driven allele

biological control


Normal Chromosome

Driven Chromosome

Recessive Female Sterility elementDrive element

biological control


biological control


EXTINCTION

biological control


EXTINCTION

Will this really work?

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

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)

˜

’ ˜

’˜ ˜

˜ ˜ ˜ ˜ ˜ ˜

˜ ˜ ˜ ˜ ˜

’

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

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

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

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

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

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

Evolutionary Engineering

Altering the course of evolution in desirable directions bymanipulating the environment and genetics ofpest organisms has begun and shows promise.

Evolutionary Engineering Mark D. Rausher Department of Biology Duke University.

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Transcript of Evolutionary Engineering Mark D. Rausher Department of Biology Duke University.