What is genetic rescue and

what is its role in

conservation?? R. Frankham

Macquarie University &

Australian Museum

Sydney, Australia

What is genetic rescue?

What is genetic rescue?

• Reversal of inbreeding and improvement

of reproductive fitness from gene flow into

inbred populations (heterosis/hybrid

vigour)

• Recovery of ability to evolve due to gene

flow into populations with low genetic

diversity (evolutionary rescue)

11 - 20 21 - 60

80 - 130

151 - 250

300 - 500

Approx. 600

Population

Size

TX

OK AR

LA

TN

MS AL

GA

FL

SC

NC

KY VA

Introduction to Conservation Genetics

Box 13.1 H vs. N in RCW.ppt

0.00

0.05

0.10

0 1 2 3 4

N

H

101100 102 103 104

What is the problem?

Innumerable species have fragmented

distributions

http://images.google.com.au/imgres?imgurl=http://www.sfrc.ufl.edu/Extension/florida_forestry_information/images/rcw3.gif&imgrefurl=http://www.sfrc.ufl.edu/Extension/florida_forestry_information/forest_resources/high_pine.html&h=731&w=500&sz=159&hl=en&start=18&tbnid=u6oNCd5Orj_F0M:&tbnh=141&tbnw=96&prev=/images%3Fq%3Dred%2Bcockaded%2Bwoodpecker%26gbv%3D2%26svnum%3D10%26hl%3Den%26sa%3DG

What are the genetic

consequences of fragmented

distributions?

• If there is no gene flow between fragments

– Inbreeding

– Loss of genetic diversity

– Reduced reproductive fitness

– Reduced ability to evolve

– Elevated extinction risks

What is the remedy?

• Re-establish gene flow (genetic rescue)

– Reduce inbreeding

– Restore genetic diversity

– Improves reproductive fitness

– Reduced ability to evolve

– Reduce extinction risk

How often is the remedy used?

• Very rarely being done • know only ~ 30 cases worldwide for thr/near thr pops

animals & plants

• Estimate that 1.4m pop fragments of thr sp would benefit from gene flow

Why are there so few genetic

rescue attempts?

1. Fears about outbreeding depression

2. Lack of clear overview of effects

3. Causal links between G divergence and low GD

4. Overly stringent guidelines

5. Concerns about maintaining genetic purity

6. Costs

7. Risks of disease transfer

8. Regulatory barriers

8

What fitness effects have

been reported on outcrossing?

Often beneficial, some harmful (OD)

Edmands (2007) variable

McClelland & Naish (2007) fish

F1 +0.26, F2 +0.16 [SD units] (CI -0.05 to +0.57), (CI – 0.41 to +0.74)

Whitlock et al. (2013) animals & plants

F1 + 1.2%, F2 -8.8% (CI -2.1 to +5.4) (CI -14 to -0.25)

Those papers don’t reflect the

conservation context • Only contemplate genetic rescue for

isolated inbred population fragments with

low genetic diversity

• Avoid crosses with a high risk of OD

• Consequently, I did a meta-analysis that

reflected the conservation context

Meta-analysis aims Evaluate genetic rescue effects in a conservation context

Does outcrossing improve the reproductive fitness

of small isolated inbred populations where risk of

OD is low?

How consistently are the effects?

How large are the effects?

What variables affect the magnitude?

Do benefits persist across generations?

Data screen in meta-analysis

• Inbred pop + outcrossed pop

• Fitness data

• Low risk of outbreeding depression

(Frankham et al. 2011)

• Same species/sub-species

• No fixed chromosomal diffs

• Adapted to similar environments

• Gene flow within last 500 yrs

• Excluded selected domestic species

Data mining yielded

• 156 fitness comparisons (going back to

Darwin 1876)

• Involving 77 taxa (18 inverts, 15 verts & 44

plants)

Effect size for fitness (∆GR)

% change in fitness

= 100 (outcrossed – inbred)

inbred

How consistent is GR?

15

Data: 145 +: 2 =: 9 – (156)

• 92.9% beneficial***

Highly consistently beneficial

effects

Screen against OD effective

What about the exceptions?

• All mildly harmful ≤ 14%

• 8/9 likely chance (low power, etc)

– 1 OD: selfing nematode:

• low ID & G rescue expected & elevated risk of OD

16

How large are GR effects?

composite fitness in

outbreeding species

• Data: 67 cf

• Median 84%*** (range -14%-∞)

• Mean 116% (CI 80%; 158%)

Wild 151%: captive 51%

(likely underestimates)

Magnitude of genetic rescue effects for

fitness Taxon ∆GR (%) Trait ΔF Breeding

system

Vertebrates

African lion 347 # cubs weaned/female NA O

Bighorn sheep 331 female annual reproductive

success

0.25 O

Desert topminnow fish 7500 total fitness NA O

European tree frog 15 tadpole body mass 0.15 O

Florida panther 169 composite fitness 0.58 O

Greater prairie chicken 26 hatching success 0.10 O

Gray wolf (Europe) 23 annual population growth 0.14 O

South Island robin 679 reproductive recruitment/egg 0.21 O

Swedish adder 233 male recruitment success 0.75 O

Invertebrates

Glanville fritillary butterfly 211 egg hatching rate 0.41 O

Mysid shrimp 318 net increase in N 0.31 O

Plants

Florida ziziphus ∞ fertilization success NA SI

Italian ryegrass 43 flowering heads/plant 0.42 SI

Jellyfish tree 151 composite fitness 0.31 SI

Partridge pea 73 total fitness 0.06 O

Small scabious 114 composite fitness 0.15 O

Water hyacinth 118 # flowers 0.97 O

Accords with fitness data in

domestic animals and plants

Maize 190% outcrossing

Sorghum 100% mainly selfing Layers 22%

Cotton 48% selfer

Wheat 29% selfer

Barley 32% selfer

Tomato 45% selfer Swine 72%

What variables affect the

magnitude?

Variables determining ID (opposite sign)

• Stressful > benign env

• Inbreeding (ΔFm & ΔFz)

• Br system (outcrossing > selfing)

• Immigrants outbred > inbred

• (ploidy)

• Major taxa ns

• Generation

Variable Median ∆GR (%) n

Mating system Outbreeding > selfing 133

Outbreeding 78.8***

Selfing or mixed mating 16.5

Immigrants Outbred > Inbred 120

Outbred 113.6***

Inbred 51.9

Major taxa (all data) 133

Invertebrates 58.4ns

Vertebrates 94.2

Plants 59.1

Variables affecting the

magnitude of GR (Frankham 2015)

Do benefits of gene flow persist

across generations?

Do benefits of gene flow persist

(outbreeders)?

Effects F1 F2 F3 Beneficial

Reduction in inbreeding (∆F)

- zygotic effects

Maximal

Stable at ~ ½-¾ F1

Stable at ~ ½-¾ F1

- maternal effects Nil Maximal Stable at ~ ½-¾ F1

Harmful

Differential adaptation

(additive)

- zygotic effects

Worst

~ ½ F1

~ ½ F1

- maternal effects Nil Worst ~ ½ F2

Fixed chromosomal

differences: ploidy

- Zygotes & maternal

Nil (soma)

Present*

Present*

: translocations, inversions

and centric fusion

- Zygotes & maternal

Nil (soma)

Worst

~ ½ F2

Coadapted gene complexes

(worsens with generations)

- Zygotes

Nil

Present

Worse

- maternal Nil Nil/minimal Present 23

Persistence of genetic rescue

benefits with selfing

GR for fitness not persist in selfing

species A1A1 x A2A2 → A1A2 and the heterozygosity halves

in each subsequent generations of selfing

Persist less in mixed-mating species

than random-mating ones (33-89%)

Benefits in F1, F2 and F3 (and

later) generations (Frankham 2016)

Generation % beneficial n Fitness

median

benefit

n

F1 90.5*** 95 42%*** 39

F2 100.0*** 13 84%* 5

F3 and later 94.1*** 17 86%*** 14

25

But what of persistence of GR

beyond F3 in outbreeders?

26

Bijlsma et al. (2010)

Benefits persist across

generations for outcrossing

species

27

What about the ability to evolve

(evolutionary rescue)?

Rescued

Not

Evolutionary rescue for fitness

benefit/G

• Consistency: 6: 0* beneficial

• Median benefit 22.4%/G

• Mean 37.6% + 16.2%

• Non-fitness traits 35: 4***

beneficial

29

Evolutionary rescue increases

with heterozygosity

Genetic rescue: conclusions

1. Highly consistent benefits of outcrossing on

fitness & evol potential

2. OD screen highly effective

3. Fitness benefits large (wild 151%)

4. Benefits = f (environment, ΔFm, ΔFz, br system,

& immigrants outbr v inbr)

5. Benefits persisted over generations for outbrs

Recommend GR for

• isolated inbred pop fragments

of outx sp,

• when proposed cross has a low

risk of OD, &

• predicted benefits justify the

costs.

Genetic Management of Fragmented

Animal and Plant Populations

Frankham, Ballou, Ralls, Eldridge, Dudash,

Fenster, Lacy & Sunnucks

Oxford University Press

How serious a problem is

inbreeding depression?

a No maternal component

Common name Genus and

species

ID

%

Red deer Cervus elaphus 99

Collared

flycatcher

Ficedula albicollis 94a

Great tit Parus major 55

Song sparrow Melospiza melodia 79

Takahe Porphyrio

hochstetteri

88

Deerhorn clarkia Clarkia pulchella 100a

Rose pink plant Sabatia angularis 38a

Wild radish Raphanus sativus 58a

34

Inbreeding and extinction

• Lab studies

• Field studies

• Simulations

0

0.5

1

0 0.5 1

F

Pro

po

rtio

n s

urv

ivin

g

FS

10

20

African lion

0

100

200

300

400

0 5 10 15 20 25

N

35

Estimation number of thr populations

that would potentially benefit from gene

flow • # benefiting = # species x P (thr) x P (frag

& isol) x av # fragments x P (inbred)

= 8.7m x 0.2 x 0.4 x 10 x 0.2

= 1.4m

Causal links between genetic

divergence & loss GD • Theory

• Empirical

Coleman et al. (2013)

T

Sp

STH

H

pqF 1

2

37

Genetic management of

fragmented populations is one

of the most important, largely

unaddressed issues in all of

conservation biology

Genetic rescue is a crucial part

of that

A paradigm shift

39

Fmaternal lags Fzygote by 1 gen

___________________________________ Generation F Litter size

Maternal Zygotic in mice

_______________________________________________

Outbred 0 0 8.1

Full-sib 3 0.375 0.50 5.7

F1 (inb x inb) 0.5 0 6.2

Inbreeding depression 8.12 - 5.69 = 2.43

F2 0 0.25 (6.7)

F1 x diff F1 0 0 8.5

Genetic rescue 8.47 – 5.69 = 2.78

_______________________________________________