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Genetic rescue can increase the fitness of small, imperiled populations via immigration. A suite of studies from the past decade highlights the value of genetic rescue in increasing population fitness. Nonetheless, genetic rescue has not been widely applied to conserve many of the threatened populations that it could benefit. In this review, we highlight recent studies of genetic rescue and place it in the larger context of theoretical and empirical developments in evolutionary and conservation biology. We also propose directions to help shape future research on genetic rescue. Genetic rescue is a tool that can stem biodiversity loss more than has been appreciated, provides population resilience, and will become increasingly useful if integrated with molecular advances in population genomics. Copyright © 2014 Elsevier Ltd. All rights reserved.
Content may be subject to copyright.
Genetic
rescue
to
the
rescue
Andrew
R.
Whiteley
1*
,
Sarah
W.
Fitzpatrick
2*
,
W.
Chris
Funk
2,3*
,
and
David
A.
Tallmon
4*
1
Department
of
Environmental
Conservation,
University
of
Massachusetts
Amherst,
Amherst,
MA
01003,
USA
2
Department
of
Biology,
Colorado
State
University,
Fort
Collins,
CO
80523,
USA
3
Graduate
Degree
Program
in
Ecology,
Colorado
State
University,
Fort
Collins,
CO
80523,
USA
4
Department
of
Biology
and
Marine
Biology,
University
of
Alaska
Southeast,
Juneau,
AK
99801,
USA
Genetic
rescue
can
increase
the
fitness
of
small,
imper-
iled
populations
via
immigration.
A
suite
of
studies
from
the
past
decade
highlights
the
value
of
genetic
rescue
in
increasing
population
fitness.
Nonetheless,
genetic
res-
cue
has
not
been
widely
applied
to
conserve
many
of
the
threatened
populations
that
it
could
benefit.
In
this
review,
we
highlight
recent
studies
of
genetic
rescue
and
place
it
in
the
larger
context
of
theoretical
and
empirical
developments
in
evolutionary
and
conserva-
tion
biology.
We
also
propose
directions
to
help
shape
future
research
on
genetic
rescue.
Genetic
rescue
is
a
tool
that
can
stem
biodiversity
loss
more
than
has
been
appreciated,
provides
population
resilience,
and
will
become
increasingly
useful
if
integrated
with
molecular
advances
in
population
genomics.
Maintaining
biodiversity
and
evolutionary
potential
Rapid
human
population
growth,
environmental
change,
and
habitat
fragmentation
all
pose
ever-greater
threats
to
biodiversity
and
highlight
the
need
for
increasingly
aggres-
sive
conservation
efforts.
Genetic
rescue
([1]
GR;
see
Glos-
sary)
has
the
potential
to
be
one
of
the
most
powerful
means
to
conserve
small
and
declining
populations,
yet
in
practice,
it
remains
controversial
[2–4]
and
is
rarely
applied.
The
debate
centers
on
whether
the
translocation
of
individuals
or
alleles
into
small,
imperiled
populations
will
have
the
desired
effect
of
increasing
population
growth
rates
and
maintaining
a
diverse
array
of
local
populations,
or
reduce
population
fitness
through
outbreeding
depres-
sion
and
decrease
biodiversity
by
homogenizing
distinct
gene
pools.
In
this
review,
we
clarify
GR
among
a
prolifer-
ation
of
related
concepts,
review
work
done
since
a
com-
prehensive
review
[5]
on
the
topic
10
years
previously,
and
identify
future
directions
for
research
and
application.
What
is
genetic
rescue?
GR
is
an
increase
in
population
fitness
inferred
from
some
demographic
vital
rate
or
phenotypic
trait,
by
more
than
can
be
attributed
to
the
demographic
contribution
of
immigrants
[5].
The
top
priority
for
preventing
the
extinction
of
small
and
imperiled
populations
is
to
reduce
extinction
risk
by
increasing
their
absolute
fitness,
measured
by
an
increase
in
population
size
or
growth
rate
[6,7].
GR
is
especially
useful
for
management
and
conservation
because
it
induces
a
population-level
demographic
response
to
the
introduction
of
new,
beneficial
alleles
via
prescribed
gene
flow
(Box
1).
GR
focuses
on
restoring
genetic
diversity
and
increasing
fitness
in
small
populations
that
are
isolated
and
typically,
but
not
necessarily,
suffering
from
inbreeding
effects
(see
Figure
IA
in
Box
1).
GR
can
occur
through
heterosis
or
adaptive
evolution.
Heterosis
occurs
from
GR
when
fitter
hybrid
offspring
from
matings
between
residents
and
immi-
grants
increase
demographic
vital
rates
relative
to
the
original
population.
Adaptive
evolution
can
also
increase
population
vital
rates
with
a
shift
towards
an
optimal
phenotype
due
to
selection
on
newly
introduced
or
recombi-
nant
genotypes.
For
example,
small
plant
populations
with
only
one
self-incompatibility
allele,
so
called
S-alleles,
can-
not
reproduce
successfully
[8].
An
infusion
of
new
S-alleles
into
this
type
of
population
would
likely
lead
to
an
adaptive
increase
in
the
frequency
of
introduced
S-alleles
and
an
increased
population
growth
rate.
This
restoration
of
popu-
lation
fitness
would
qualify
as
GR,
even
though
alleviation
of
inbreeding
depression
was
not
the
mechanism
responsible.
Review
Glossary
Absolute
fitness:
mean
number
of
offspring
per
capita,
measured
as
population
growth
rate
(l)
or
abundance
(N).
Adaptive
evolution:
an
increase
in
beneficial
phenotypes
in
a
population
as
a
result
of
natural
selection
on
genetic
variation.
Adaptive
management:
a
structured,
iterative
process
of
decision-making
that
includes
system
monitoring
to
reduce
uncertainty.
Assisted
gene
flow:
managed
movement
of
individuals
into
populations
to
reduce
local
maladaptation
to
climate
or
other
environmental
change.
Epistatic
load:
combinations
of
alleles
at
different
loci
that
reduce
fitness.
Evolutionary
rescue:
an
increase
in
population
growth
resulting
from
adaptation
to
otherwise
extinction-causing
environmental
stress
from
standing
genetic
variation,
de
novo
mutation
or
gene
flow.
Genetic
load:
the
relative
difference
in
fitness
between
the
theoretically
fittest
genotype
and
the
average
genotype
in
a
population.
Caused
by
deleterious
alleles
in
the
case
of
mutational
load.
Other
types
of
load
include
segregation,
drift,
epistatic,
and
migration.
Genetic
rescue:
an
increase
in
population
fitness
(growth)
owing
to
immigra-
tion
of
new
alleles.
Genetic
restoration:
an
increase
in
genetic
variation
and
relative,
but
not
absolute,
fitness
owing
to
immigration
of
new
alleles.
Heterosis:
elevated
fitness
of
offspring
from
matings
between
genetically
divergent
individuals.
Invasive
hybridization:
cross-breeding
between
invasive
and
native
species.
Outbreeding
depression:
reduced
fitness
of
offspring
from
matings
between
genetically
divergent
individuals.
Transgressive
hybridization:
the
creation
of
hybrids
with
phenotypes
more
extreme
than
their
parental
lines.
0169-5347/
ß
2014
Elsevier
Ltd.
All
rights
reserved.
http://dx.doi.org/10.1016/j.tree.2014.10.009
Corresponding
author:
Tallmon,
D.A.
(david.tallmon@uas.alaska.edu).
Keywords:
genetic
rescue;
inbreeding
depression;
outbreeding
depression;
heterosis;
adaptive
evolution;
endangered
species;
evolutionary
rescue.
*
These
authors
contributed
equally.
TREE-1881;
No.
of
Pages
8
Trends
in
Ecology
&
Evolution
xx
(2014)
1–8
1
The
important
outcome
for
GR
is
that
gene
flow
leads
to
an
increase
in
population
growth
rate
above
and
beyond
the
demographic
effect
of
immigrants.
Whether
the
growth
occurs
as
a
result
of
heterosis
or
adaptive
evolution
is
often
difficult
to
distinguish
in
wild
populations
because
it
requires
careful
experimental
matings.
GR
is
related
to,
but
distinct
from,
a
recent
surge
of
related
terminology
that
surrounds
growing
empirical
evidence
that
populations
can
respond
rapidly
to
natural
selection
follow-
ing
the
addition
of
genetic
variation
from
mutation
or
gene
flow
[9,10]
(Box
1).
For
example,
it
is
possible
for
gene
flow
to
restore
levels
of
genetic
variation,
but
not
increase
popula-
tion
growth
(genetic
restoration;
Box
1)
[11,12].
GR
is
par-
ticularly
closely
related
to
the
concept
of
evolutionary
rescue
(ER),
which
has
been
defined
as
an
adaptation-dependent
reversal
of
demographic
decline
due
to
maladaptation
to
novel
environmental
conditions
[9,10].
ER
emphasizes
the
demographic
benefits
of
genetic
variation,
regardless
of
whether
the
source
of
variation
is
immigration
or
arises
within
a
population
by
de
novo
mutation
or
recombination
of
existing
variation.
ER
also
requires
an
environmental
shift
and
rescue
from
extinction
must
occur
via
adaptive
evolution
to
that
changed
environment
[10].
Our
definition
of
GR
is
the
same
as
some
previous
defini-
tions
[5],
but
differs
from
definitions
that
restrict
GR
to
solely
focusing
on
alleviation
of
inbreeding
depression
[10].
Although
there
is
broad
overlap
between
our
definition
of
GR
and
ER
when
caused
by
immigration,
ER
(with
immigration)
is
arguably
more
restrictive
than
GR
because
of
ER’s
dependence
on
adaptive
response
to
a
shifting
environment.
In
the
S-allele
example,
the
adaptive
shift
in
S-allele
frequencies
would
not
qualify
as
ER
because
the
adaptive
change
was
not
related
to
an
environmental
shift.
ER
spurred
by
extant
genetic
variation
or
mutation
is
unlikely
to
prevent
extinction
in
small,
genetically
depau-
perate
populations
because
they
are
unlikely
to
have
suffi-
cient
genetic
variation
to
adapt
to
new
environmental
conditions
[9].
When
small,
extinction-prone
populations
are
the
focus,
immigration
(in
many
cases
human
mediated)
is
likely
to
be
necessary
to
provide
sufficient
genetic
varia-
tion
on
which
selection
can
act
and
result
in
population
growth
[13].
Given
the
broad
overlap
between
ER
(with
immigration)
and
GR
(as
defined
here)
when
applied
to
small
populations
of
conservation
concern,
we
suggest
that
there
are
many
opportunities
for
enhanced
understanding
and
cross-collaborations
among
researchers
working
on
these
concepts.
Ten
years
of
genetic
rescue
studies
Tests
based
on
outcrossing
experiments
An
important
point
is
that
GR
rests
not
upon
outcrossing
large
numbers
of
individuals,
but
upon
the
introgression
of
Box
1.
Genetic
rescue
and
related
concepts
Small
populations
in
need
of
genetic
rescue
have
low
genetic
variation,
low
fitness,
and
low
phenotypic
variation
(Figure
IA).
Successful
GR
involves
an
increase
in
abundance,
reflecting
an
increase
in
absolute
fitness
of
the
small
population
(Figure
IB).
Admixture
and
increased
individual
(relative)
fitness
of
admixed
individuals
(a
shift
towards
a
locally
adaptive
peak),
but
a
lack
of
increased
population
growth
result
in
genetic
restoration
(Figure
IC,
distribution
I),
not
GR.
For
Isle
Royale
wolves,
the
infusion
of
genetic
variation
increased
individual
fitness
metrics
and
slowed
population
decline
whereas
other
factors,
such
as
deteriorating
environmental
conditions,
prevented
the
population
from
expanding
[11].
Another
potential
outcome
is
that
too
much
gene
flow
leads
to
extensive
hybridization
(swamping),
in
which
case
the
population
moves
away
from
the
adaptive
peak,
and
abundance
remains
low
(Figure
IC,
distribution
II).
GR
with
too
much
gene
flow
can
resemble
potential
negative
effects
of
invasive
hybridization
[57]
A
closely
related
term
to
GR
is
assisted
gene
flow
(AGF;
[53]).
Aitken
and
Whitlock
[53]
defined
AGF
as
the
managed
movement
of
individuals
or
gametes
between
populations
within
species
ranges
to
mitigate
local
maladaptation
in
the
short
and
long
term.
AGF
differs
from
GR
in
the
emphasis
placed
on
the
introduction
of
alleles
and
genotypes
that
are
pre-adapted
to
new
(altered)
local
climates
(Figure
ID
[53]).
To
demonstrate
this
difference,
we
assume
that
environmental
change
(shift
from
gray
to
black
fitness
function
in
Figure
ID)
causes
a
formerly
locally
adapted
population
to
be
maladapted
and
shrink
in
abundance
(black
distribution;
Figure
ID).
GR
prescribes
the
addition
of
individuals
from
matched
current
environments,
such
that
restored
genetic
diversity,
alleviated
inbreeding
depression,
and
a
subsequent
adaptive
response
enable
population
growth
(red
distribution
in
Figure
ID).
Source
popula-
tions
for
AGF
are
chosen
such
that
their
historical
environments
are
similar
to
the
already
changed
environment
in
Figure
ID
(black
fitness
function).
A
major
challenge
for
implementation
of
AGF
will
be
meeting
the
necessary
high
degree
of
understanding
of
local
adaptation
to
past
and
future
conditions,
as
well
as
overcoming
the
enhanced
probability
of
outbreeding
depression
that
comes
from
choosing
geographically
distant
but
potentially
climate-matching
sources
of
gene
flow
[53,56].
Evolutionary
rescue
(ER)
involves
the
same
distribution
shift,
but
ER
would
rely
on
standing
genetic
variation,
de
novo
mutation,
or
immigration.
For
isolated
popula-
tions
with
low
genetic
diversity
and
high
inbreeding
coefficients,
ER
is
unlikely
to
be
successful
without
external
input
of
genetic
diversity
[9].
Abundance
Abundance
Abundance
Abundance
Phenotype
Phenotype
Phenotype
Phenotype
(A)
(D)
(B)
(C)
III
TRENDS in Ecology & Evolution
Figure
I.
The
fitness
of
individuals
with
a
given
phenotype
is
shown
by
the
relation
between
the
distribution
of
phenotypes
(numbers
of
individuals
or
abundance)
and
the
fitness
function
(broken
lines)
for
a
given
environment.
(A)
represents
a
small,
imperiled
population
with
reduced
phenotypic
and
genetic
variation
that
could
benefit
from
genetic
rescue.
(B)
represents
successful
genetic
rescue,
with
an
increase
fitness
following
prescribed
gene
flow.
(C)
represents
genetic
restoration
(distribution
I)
or
genetic
swamping
(distribution
II).
Shown
in
(A),
(B),
and
(C)
are
recipient
(black),
donor
(light
gray),
and
admixed
(gray)
genomes.
Both
(B,C)
show
the
hypothetical
outcome
of
human-mediated
gene
flow
a
short
period
(approximately
five
generations)
following
initiation.
The
size
of
shaded
areas
is
meant
as
a
heuristic
guide
and
will
vary
case-by-case.
An
environmental
shift
in
(D)
is
shown
by
a
shift
in
the
peak
of
the
original
fitness
function
(gray
broken
line)
to
the
left
(black
broken
line;
shift
shown
with
black
arrow).
The
black
distribution
shows
a
population
now
maladapted
and
at
low
abundance
following
the
environmental
change
(black
distribution).
The
red
arrow
shows
the
desired
extirpation-avoiding
shift
in
population
phenotype
and
abundance
(red
distribution)
following
assisted
gene
flow.
Review Trends
in
Ecology
&
Evolution
xxx
xxxx,
Vol.
xxx,
No.
x
TREE-1881;
No.
of
Pages
8
2
beneficial
genetic
variation
from
a
small
number
of
immi-
grants
so
that
locally
adaptive
variation
is
not
swamped
[2,5].
In
theory,
low
levels
of
immigration
should
be
ade-
quate
to
decrease
the
frequency
of
deleterious
alleles
and
provide
increased
genetic
variation
for
selection
to
act
upon,
leading
to
increased
population
fitness.
By
contrast,
most
experiments
use
large
numbers
of
outcrosses,
which
increases
the
odds
of
finding
an
effect
of
outcrossing
(Table
S1
in
the
supplementary
material
online).
Nonethe-
less,
general
patterns
that
emerge
from
outcrossing
experi-
ments
remain
relevant
to
GR.
Many
experiments
have
tested
the
relative
fitness
effects
of
outcrossing
large
num-
bers
of
individuals
in
the
past
10
years
(Table
S1).
Al-
though
outbreeding
depression
is
a
threat
to
locally
adapted
populations
[3–5],
outcrossing
tends
to
boost
mo-
lecular
genetic
variation
and
mean
individual
fitness-re-
lated
traits
for
individuals,
particularly
those
from
inbred
populations
[14–20]
(Table
S1).
While
this
relative
fitness
boost
following
outcrossing
is
not
universal
for
all
traits,
individuals,
and
populations,
it
is
often
found
when
mea-
sured
across
multiple
traits,
individuals,
and
populations
(Table
S1).
Most
studies
have
tracked
the
relative
fitness
of
a
large
number
of
hybrids
for
one
generation
(F
1
),
leaving
the
longer-term
effects
of
small
amounts
of
outcrossing
rela-
tively
untested
(Table
S1).
In
some
recent
cases,
fitness
benefits
have
been
found
beyond
the
first
generation,
suggesting
that
outbreeding
depression
should
not
be
as
much
of
a
concern,
and
that
selection
on
new
recombinant
genotypes
can
be
more
beneficial
than
was
previously
thought
[21,22].
For
example,
outcrossing
individuals
of
the
rare
buttercup
Ranunculus
reptans
led
to
mean
fitness
boosts
through
the
F
2
generation,
especially
for
individuals
from
small
populations
[22].
Drosophila
populations
showed
increased
viability
five
and
10
generations
after
a
prescribed
gene
flow
event,
even
though
immigrants
were
from
inbred
sources
[18].
Outcrossed
copepod
(Tigriopus
californicus)
and
pea
(Chamaecrista
fasciculata)
popula-
tions
also
showed
elevated
fitness
relative
to
control
popu-
lations
several
generations
following
outcrossing,
because
of
selection
on
recombinant
genotypes
[21,23].
Tests
based
on
small
numbers
of
immigrants
Increased
within-population
genetic
variation
has
been
observed
following
translocations
or
natural
immigration
of
small
numbers
of
individuals
into
wild
populations
[20,24–29].
Adding
individuals
or
alleles
into
isolated
populations
across
a
range
of
taxa
and
life
histories
has
led
to
increases
in
fitness-related
traits
[18–20,24–26,
28,30–33].
These
boosts
can
be
especially
dramatic
when
the
source
population
is
large
and
the
target
population
is
small
and
inbred
[19,30],
exactly
the
conditions
under
which
GR
should
be
most
effective.
The
next
step
of
quan-
tifying
the
absolute
fitness
effect
of
limited
immigration
across
multiple
generations
is
difficult
for
most
wild
popu-
lations,
especially
for
species
with
generation
lengths
of
many
years
[16].
Furthermore,
it
is
difficult
to
replicate
GR
among
populations
with
experimental
controls
that
allow
one
to
isolate
relative
and
absolute
fitness
effects
of
small
amounts
of
gene
flow
and
infer
causation
with
adequate
statistical
power.
Our
literature
search
revealed
that
studies
that
have
rigorously
tested
for
absolute
fitness
effects
of
low
levels
of
migration
across
generations
remain
rare
(18
sets
of
cross-
ing
experiments
or
monitored
immigration
events
involv-
ing
15
species;
Table
1).
The
majority
(14/18;
78%)
of
these
sets
of
crossing
experiments
or
monitored
immigration
events
showed
either
positive
(n
=
10)
or
a
mix
of
positive
and
no
(‘N’)
(n
=
4)
absolute
fitness
effects
(Table
1).
For
the
latter,
studies
tended
to
find
positive
relative
fitness
effects
Table
1.
Summary
of
studies
that
report
absolute
fitness
effects
of
gene
flow
a
Species
Study
type
b
No.
of
migrants
Length
c
Absolute
fitness
metric
Absolute
fitness
effect
d
Refs
Common
name
Latin
name
Bacteria Pseudomonas
pseudoalcaligenes
exp
phage
insertions
not
measured
population
size
+
[58]
Beach
clustervine Jacquemontia
reclinata
exp
crosses
F1
population
growth
rate
+/N
[59]
Flour
beetle Tribolium
castaneum
exp
20–45
F1–F24
population
growth
rate
+/N
[60]
Guppy Poecilia
reticulata
exp
2
F1
population
size
+
[16]
Hoary
sunray Leucochrysum
albicans
exp
crosses
F1
population
size
+/N
[61]
Marine
copepod Tigriopus
californicus
exp
crosses
F1–F20
population
size
+
[23]
Marine
copepod Tigriopus
californicus
exp
crosses
F1–F20
population
size
[35]
Wood
rat Neotoma
magister
exp
10
F1
population
size
+
[39]
Yeast Saccharomyces
cerevisiae
exp
crosses
F1
population
growth
rate
+/–
[62]
Yeast Cryptococcus
neoformans
exp
crosses
unknown
colony
size
N
[63]
Adder Vipera
berus
obs
20
F1
population
size
+
[36,37]
Bighorn
sheep Ovis
canadensis
obs
15
F2
population
size
+
[24,27]
Florida
panther Puma
concolor
coryi
obs
8
F2
population
size
+
[26]
Gray
wolf Canis
lupus
obs
1
F2
population
size
N
[11]
Mexican
wolf Canis
lupus
baileyi
obs
crosses
F1
population
size
N
[34]
Prairie
chicken Tympanuchus
cupido
obs
271
F6
population
size
+
[25,38]
Scandinavian
wolf Canis
lupus
obs
1
F2
population
size
+
[64]
a
All
studies
reported
in
[5]
that
measured
absolute
fitness
and
studies
since
2004
that
meet
our
search
criteria
(Table
S1)
and
measured
absolute
fitness.
Each
row
corresponds
to
a
separate
set
of
experimental
crosses
or
an
immigration
event
with
the
number
of
migrants
shown.
b
Abbreviations:
Exp,
experimental;
Obs,
observational.
c
Study
length
in
generations
following
immigration
or
crossing.
d
Measured
fitness
effect
as
beneficial
(+),
negative
(–),
or
none
(N).
Review Trends
in
Ecology
&
Evolution
xxx
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Vol.
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No.
x
TREE-1881;
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Pages
8
3
following
crossing
or
immigration
that
did
not
translate
to
a
population-level
response,
consistent
with
what
we
de-
fine
as
genetic
restoration.
Genetic
restoration
was
also
observed
in
two
of
the
three
studies
categorized
solely
as
‘N’
[11,34].
Only
one
study
reported
a
negative
absolute
fitness
response
(outbreeding
depression)
[35].
This
study
is
note-
worthy
because
the
authors
chose
populations
that
would
be
nearly
incompatible
and
were
highly
genetically
diver-
gent
[21%
sequence
divergence
at
the
cytochrome
oxidase
I
(COI)
gene].
Populations
this
divergent
would
be
unlikely
to
be
considered
for
GR.
Intensive
studies
of
single
populations
of
charismatic
megafauna
provide
some
of
the
examples
of
favorable
population-level
fitness
responses
to
low
levels
of
immigra-
tion
[24–26,29,36–39]
(Table
1).
High-profile
recent
exam-
ples
include
increased
genetic
variation
and
population
growth
responses
to
translocations
of
individuals
into
Florida
panther
Felis
concolor
coryi
[26]
(Box
2)
and
Rocky
Mountain
bighorn
sheep
Ovis
canadensis
[24,27]
popula-
tions.
Hybrid
offspring
from
immigrant
resident
crosses
had
higher
measures
of
genetic
variation
and
superior
fitness
that
led
to
increases
in
demographic
rates
and
absolute
population
fitness.
In
the
case
of
the
Florida
panther,
genetic,
ecological,
and
demographic
studies
have
been
exhaustive
and
encouraging
(Box
2).
The
downside
of
all
unreplicated
and
uncontrolled
studies
of
single
popula-
tions
is
that
assigning
definitive
causal
relations
is
impos-
sible
[40].
For
example,
increases
in
population
growth
could
be
the
result
of
favorable
environmental
factors.
However,
these
studies
provide
high
media
exposure
examples
that,
when
analyzed
collectively
for
the
demo-
graphic
and
genetics
insights
that
they
provide,
suggest
that
GR
is
a
powerful
means
to
support
small,
imperiled
populations
and
could
be
employed
more
widely.
They
also
imply
that
GR
has
repercussions
beyond
population
dy-
namics
to
affect
ecosystem
dynamics,
if
GR
can
save
eco-
logically
important
species
such
as
top
predators
(Box
3).
The
ability
to
follow
the
population-level
fitness
con-
sequences
of
immigration
for
many
generations
across
replicate
treatment
and
control
populations
highlights
the
value
of
experimental
studies
of
GR
in
lab
species
with
short
generation
times
(Box
4).
For
example,
inbred
fruit
fly
(Drosophila
melanogaster)
populations
showed
increased
viability
several
generations
following
a
10%
immigration
event,
though
this
study
did
not
estimate
absolute
fitness
[18].
Inbred
guppy
(Poecilia
reticulata)
populations
exhibited
more
complicated
sex-specific
responses
to
immigration,
but
populations
that
received
immigrants,
whether
male
or
female
grew
faster
com-
pared
with
control
populations
without
immigration
[16].
Different
population
growth
responses
depending
upon
the
sex
of
the
immigrants
suggests
that
not
all
immigrants
are
equal,
and
emphasizes
that
specific
life
histories
and
context-specific
considerations
must
be
made
to
maximize
the
benefits
and
minimize
the
risks
of
GR
[3,5,41].
Threats
from
outbreeding
depression
Among
the
primary
concerns
with
GR
attempts
is
out-
breeding
depression.
This
has
a
sound
theoretical
and
empirical
basis
[3,18,35,42,43],
but
the
pendulum
appears
to
be
swinging
away
from
these
concerns
in
light
of
evi-
dence
that
re-establishing
gene
flow
among
relatively
re-
cently
connected
populations
will
often
increase
fitness
[4,22,23].
Although
genomics
is
improving
our
ability
to
characterize
the
genetic
basis
of
adaptation
(see
below),
a
general
rule
is
that
outbreeding
depression
risk
generally
increases
with
genetic,
geographic,
and
environmental
distance
because
these
are
hopeful
surrogates
for
adaptive
differences
that
can
be
difficult
to
determine
[3,4,43].
Most
empirical
examples
of
outbreeding
depression
occur
when
populations
are
geographically
distant
and
genetically
divergent
(e.g.,
Tigriopus
californicus
populations
[23,35]),
or
when
life
history
or
phenological
differences
are
large).
Crosses
between
domestic
and
wild
individuals
also
often
result
in
negative
fitness
consequences
for
hy-
brid
offspring
(e.g.,
[44]),
especially
when
fitness
is
mea-
sured
in
the
wild.
Ideally,
small
numbers
of
immigrants
Box
2.
Insights
from
the
Florida
panther
Of
all
the
studies
of
imperiled
charismatic
species,
perhaps
the
best-
known
case
of
immigration
and
subsequent
fitness
rebound
is
that
of
the
Florida
panther
Figure
I.
Several
important
fitness-related
traits,
molecular
genetic
variation,
and
abundance
rebounded
in
the
previously
highly
inbred
population
of
approximately
22
Florida
panthers,
following
the
translocation
of
eight
panthers
from
Texas
[26].
Individual
panthers
with
greater
admixture
showed
higher
survival
than
purebred
residents,
the
population
tripled
in
size,
and
morphological
correlates
of
inbreeding
declined
after
the
transloca-
tion
effort.
Detailed
and
rigorous
demographic
analyses
suggest
that
an
annual
population
growth
rate
of
4%
replaced
a
5%
population
decline
following
translocation,
resulting
from
higher
survival
of
admixed
F
1
individuals
[28].
All
told,
this
GR
effort
was
a
success.
As
a
consequence
of
the
overwhelming
success
of
GR
for
Florida
panthers,
habitat
loss
because
of
development
in
the
north
of
the
state
and
sea
level
rise
in
the
south
will
remain
the
primary
concern
into
the
near
future
[26,28,65].
Despite
recent
rapid
population
growth,
a
failure
to
escape
small
population
size
in
the
near
future
seems
likely
to
return
the
population
to
high
levels
of
inbreeding,
and
require
another
GR
attempt
[18,66].
This
potential
for
a
cycle
of
inbreeding
depression
at
limited
population
size,
followed
by
fitness
(demographic)
decline,
and
subsequent
GR,
recalls
the
original
extinction
vortex
[6],
except
that
extinction
is
temporarily
avoided
via
GR.
The
only
way
out
of
this
intensive
management
cycle
is
to
add
habitat
and
populations
with
gene
flow
among
them.
TRENDS in Ecology & Evolution
Figure
I.
Florida
panthers
have
recently
shown
positive
demographic
responses
to
gene
flow,
including
greater
survival
and
population
growth.
Review Trends
in
Ecology
&
Evolution
xxx
xxxx,
Vol.
xxx,
No.
x
TREE-1881;
No.
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Pages
8
4
chosen
for
GR
will
originate
from
other
wild
populations
that
experience
environmental
conditions
that
are
best
matched
to
the
recipient
environment.
The
mechanisms
underlying
GR
and
outbreeding
de-
pression
may
have
different
implications
for
the
ultimate
long-term
effects
of
gene
flow
on
population
fitness.
Al-
though
teasing
apart
the
mechanisms
is
difficult
and
often
not
possible
in
management
scenarios,
heterosis
and
adap-
tive
evolution
operate
dynamically
on
different
time
frames.
Heterosis
is
maximized
in
the
F
1
generation,
whereas
adaptive
evolution
typically
requires
from
several
to
many
generations.
This
reinforces
the
need
to
test
for
effects
of
GR
over
multiple
generations.
An
initial
increase
in
fitness
of
early-generation
hybrids
may
not
persist
over
multiple
generations
if
co-adapted
gene
complexes
are
broken
apart
through
recombination.
Additionally,
ini-
tially
maladapted
immigrants
could
reduce
population
fitness
or
introduce
deleterious
alleles
that
rise
to
high
frequency
[2].
In
these
situations,
the
optimal
outcome
is
for
selection
and
recombination
to
facilitate
GR
over
time
Box
3.
Multilevel
‘eco–evo’
processes
via
genetic
rescue
Successful
genetic
rescue
inevitably
increases
genetic
diversity,
should
generally
increase
effective
population
size
(N
e
)
and,
by
our
definition,
also
increases
population
size
(N).
Ideally,
simultaneous
changes
in
genetic
and
demographic
trajectories
following
genetic
rescue
bolster
the
chances
for
imperiled
populations
to
persist
(Figure
IA).
Yet
another
potential
outcome
of
successful
GR
is
the
maintenance
of
community
processes,
also
through
genetic
and
demographic
factors
(Figure
IB).
The
increase
in
genetic
variation
attributed
to
GR
can
provide
or
restore
individual
variation
in
traits,
such
as
resource
use,
behavior,
or
morphology,
that
contribute
to
the
functional
role
of
that
species
within
its
community.
Furthermore,
demographic
patterns
of
coexisting
species
are
known
to
co-vary,
most
famously
through
predator–prey
dynamics.
By
increasing
the
abundance
of
potentially
key
players
in
such
dynamics,
genetic
rescue
could
diminish
the
risk
of
trophic
collapse
[67].
Monitoring
community-level
responses
to
the
implementation
of
genetic
rescue
could
add
to
the
argument
for
its
use
as
an
effective
management
tool
or,
alternatively,
highlight
cases
where
genetic
rescue
increases
fitness
for
the
target
species
but
disrupts
the
community
in
other
ways.
Unfortunately,
even
when
population
and
community
dynamics
are
well
studied,
the
use
of
GR
as
a
management
tool
may
be
rejected.
This
appears
to
be
the
case
in
the
recent
management
decision
not
to
augment
the
isolated
and
inbred
Isle
Royale
wolf
population
even
though
moose
herds
have
increased
in
size
as
wolf
abundance
has
declined,
and
wolf
inbreeding
coefficients
and
bone
deformities
have
increased
[11,12,68].
This
may
well
turn
out
to
be
a
missed
opportunity
to
save
this
imperiled
population
from
extinction.
Genec
Rescue
response to selecon
inbreeding depression
-
(A) Populaon persistance
individual niche paroning
potenal for coevoluon
+
+
+
(B) Community processes
stochasc reslience
Allee effects
+
-predator-prey dynamics
dispersal
+
+
genecs
demography
TRENDS in Ecology & Evolution
Figure
I.
The
benefits
of
genetic
rescue
include
an
increase
in
genetic
diversity
and
an
increase
in
abundance
of
individuals.
Positive
effects
of
genetic
rescue
on
population
persistence
(A)
can
propagate
to
influence
community
processes
(B).
Box
4.
Elegant
experiments
Experimental
studies
have
tested
GR
for
multiple
generations
under
controlled
conditions.
The
ability
to
follow
the
effects
of
immigration
over
multiple
generations
for
many
replicate
populations
is
high-
lighted
by
a
study
of
a
rare
perennial
plant
Rutidosis
leptorrhynch-
oides
(Asteraceae)
by
Pickup
and
Field
[30].
They
performed
2455
experimental
crosses
between
12
population
pairs
(only
15
populations
of
this
species
remain)
and
reared
F
1
,
F
2
,
F
3
,
and
backcrosses
in
a
greenhouse.
Populations
were
<1–600
km
apart
along
a
north–south
gradient.
Inbreeding,
genetic
diversity,
and
size
of
the
source
population
best
predicted
heterosis
across
fitness
components.
Furthermore,
heterosis
was
greater
when
the
donor
populations
were
large
with
high
genetic
diversity
and
low
inbreed-
ing
and
the
recipient
population
was
small
and
inbred.
Interestingly,
there
was
no
evidence
of
outbreeding
depression.
Geographic
distance
among
sites
was
not
an
important
predictor
of
fitness.
However,
this
study
did
not
explicitly
take
into
account
genetic
or
adaptive
divergence
between
crossed
populations.
In
another
experimental
study
of
immigration,
Hwang
et
al.
[23]
examined
controlled
crosses
(F
1
–F
3
)
and
long
term
(15
months
or
approximately
20
generations)
freely
mating
experimental
hybrid
populations
of
the
copepod
(Tigriopus
californicus).
Earlier
work
for
this
species
demonstrated
high
F
1
hybrid
fitness
followed
by
outbreeding
depression
in
the
F
2
,
possibly
because
of
drift-induced
high
genetic
load
(accumulation
of
deleterious
recessive
alleles)
and
epistatic
load
(accumulation
of
maladaptive
allele
combinations).
A
series
of
controlled
crosses
matched
a
pattern
of
outbreeding
depression
in
the
F
2
followed
by
recovery
in
the
F
3
.
Of
experimental
hybrid
populations
(50:50
or
80:20)
surviving
to
15
months
(N
=
6),
half
had
at
least
a
12-fold
greater
abundance
compared
with
surviving
midparent
treatments.
The
surviving
freely
mating
and
highly
introgressed
experimental
populations
showed
fitness
de-
clines
at
3
months
followed
by
recovery
and
higher
fitness
than
midparents
by
15
months
(20
generations),
because
of
selection
on
recombinant
genotypes.
These
results
suggest
that,
given
large
enough
population
sizes,
recombination
and
selection
within
hybrid
populations
can
allow
recovery
from
early
outbreeding
depression.
A
companion
study
[35]
showed
decreased
fitness
following
experimental
mixing
of
two
more
genetically
divergent
populations,
demonstrating
the
need
to
take
into
account
genetic
divergence
of
the
recipient
and
donor
sources.
Interestingly,
this
work
suggests
that
morphological
and
fitness
outcomes
of
crosses
are
difficult
to
predict
in
crosses
where
genetic
drift
has
a
large
role
(compared
with
more
repeatable/predictable
results
from
crosses
in
large
effective
populations
[45]).
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&
Evolution
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5
following
immigration
events.
Furthermore,
transgressive
hybridization
could
produce
individuals
with
new
genetic
combinations
and
outlier
phenotypes
that
facilitate
expan-
sion
into
a
new
ecological
niche,
especially
as
environments
shift
with
climate
change
[45,46].
It
seems
likely
that
concerns
about
outbreeding
depression
have
limited
efforts
to
use
GR
as
a
management
tool,
but
practical
guidelines
for
GR
application
have
been
created
that
should
reduce
uncertainty
about
when
it
is
appropriate
and
facilitate
its
proper
use
[41].
Genetic
rescue
in
the
genomics
era
How
will
genomics
improve
implementation
of
genetic
rescue?
Over
the
past
decade,
genomics
has
revolutionized
the
life
sciences.
The
combination
of
massive
amounts
of
genomic
data
[e.g.,
single
nucleotide
polymorphism
(SNP)
geno-
types
from
thousands
to
millions
of
loci]
and
the
computa-
tional
tools
to
analyze
these
data
is
rapidly
improving
our
ability
to
address
long-standing
questions
in
evolution,
ecology,
and
conservation.
The
subfield
of
GR
is
no
excep-
tion.
In
this
section,
we
focus
on
two
ways
in
which
geno-
mics
will
improve
the
implementation
and
effectiveness
of
GR:
(i)
via
improving
the
identification
of
the
best
source
populations
and
even
the
best
individuals
to
use
for
GR;
and
(ii)
via
improving
our
ability
to
monitor
the
outcome
of
GR
attempts
so
that
managers
can
adjust
strategies
as
necessary.
Identification
of
the
best
source
population
for
genetic
rescue
using
genomics
One
way
in
which
genomics
will
increase
the
effectiveness
of
GR
is
by
identifying
which
potential
source
populations
are
most
likely
to
have
the
desired
effect
of
increasing
fitness
and
population
growth
rate
in
the
declining
target
population.
It
is
helpful
to
know
the
level
of
adaptive
divergence
between
candidate
source
populations
and
the
target
population
to
predict
the
risk
of
outbreeding
depression.
However,
characterizing
adaptive
divergence
can
be
difficult
or
impossible
for
species
of
conservation
concern
using
traditional
approaches
such
as
reciprocal
transplant
experiments.
Genomics
now
enables
characterization
of
adaptive
dif-
ferentiation
in
species
for
which
reciprocal
transplant
experiments
are
not
practical
[47,48].
In
particular,
by
using
genome
scans
with
thousands
of
SNP
loci,
high
F
ST
outliers
can
be
identified
that
are
adaptive
or
linked
to
adaptive
loci
[49–52].
These
loci
can
then
be
used
to
estimate
how
adaptively
divergent
various
potential
source
populations
are
from
the
target
population
using
various
analyses,
such
as
population
dendrograms,
multi-
variate
approaches,
or
clustering
algorithms
[48].
To
mini-
mize
outbreeding
depression,
the
population
with
the
lowest
level
of
adaptive
differentiation
from
the
target
population
would
be
chosen.
Alternatively,
from
the
per-
spective
of
assisted
gene
flow,
the
goal
would
be
to
choose
individuals
from
an
adaptively
divergent
source
popula-
tion
that
has
alleles
predicted
to
be
adaptive
under
future
environmental
conditions
in
the
target
population
[53].
This
may
be
a
viable
strategy
for
organisms
with
large
populations
and
high
fecundity
(e.g.,
some
forest
trees),
because
inbreeding
rates
should
be
low
and
selec-
tion
can
overwhelm
genetic
drift.
However,
for
small
and
isolated
populations,
it
may
be
more
effective
to
alleviate
inbreeding
depression
by
introducing
immigrants
adapted
to
the
current
environment,
so
that
the
population
will
persist
and
grow,
thereby
increasing
the
potential
for
adaptation
to
future
environmental
change.
More
work
is
needed
to
learn
how
best
to
use
outlier
loci
and
other
adaptive
loci
to
characterize
adaptive
differentiation,
but
early
results
suggest
that
this
approach
has
potential
[48,54].
Identification
of
the
best
source
individuals
for
genetic
rescue
using
genomics
Once
a
source
population
is
chosen
for
GR,
genomics
will
also
help
identify
which
individuals
are
most
likely
to
reduce
inbreeding
depression
and
thereby
increase
fitness
and
population
growth
rates
in
the
target
population.
Importantly,
all
individuals
in
the
source
population
are
not
necessarily
equal
in
terms
of
their
capacity
to
reduce
inbreeding
depression
in
the
target
population.
Some
in-
dividuals
will
have
more
alleles
predicted
to
reduce
in-
breeding
depression,
for
example
by
masking
the
deleterious
recessive
alleles
fixed
in
individuals
in
the
target
population
[47].
However,
knowing
which
alleles
and,
therefore,
which
individuals,
will
reduce
inbreeding
depression
first
requires
understanding
the
genetic
basis
of
inbreeding
depression
in
the
target
population.
With
genomics,
it
is
possible
to
select
individuals
with
the
highest
genome-wide
diversity
or
to
link
fitness
to
specific
alleles
and
genotypes
at
thousands
of
loci
across
the
genome,
for
example
using
association
mapping
[47].
Once
the
main
loci
underlying
inbreeding
depression
are
identified,
it
would
then
be
possible
to
screen
poten-
tial
source
individuals
at
these
loci
to
identify
those
individuals
with
the
combination
of
alleles
at
multiple
loci
predicted
to
reduce
inbreeding
depression
the
most.
Hand
picking
source
individuals
for
genetic
rescue
based
on
their
genotypes
will
be
particularly
effective
in
cases
in
which
inbreeding
depression
is
primarily
determined
by
relatively
few
loci
of
large
effect.
However,
given
that
inbreeding
depression
can
be
caused
by
any
number
of
loci
that
influence
survival
or
reproduction,
we
might
find
that
many
loci
of
small
effect
are
responsible
for
reduced
fitness
with
inbreeding.
In
this
case,
it
may
prove
difficult
to
perform
this
type
of
screening
for
organ-
isms
of
conservation
concern.
Furthermore,
other
nonge-
netic
factors
will
also
need
to
be
considered
when
choosing
individuals
for
GR,
such
as
their
sex,
age,
and
reproductive
potential.
However,
if
possible,
picking
individuals
with
genotypes
predicted
to
reduce
inbreeding
depression
the
most
could
improve
the
effectiveness
of
genetic
rescue.
Recently,
it
has
been
suggested
that
alleles
predicted
to
reduce
inbreeding
depression
could
be
transgenically
added
to
individuals
suffering
from
inbreeding
depression
[55].
Many
technical
hurdles
must
be
overcome
before
this
will
be
feasible
and
affordable.
Thus
for
now,
we
recom-
mend
focusing
on
identifying
and
introducing
individuals
with
the
combination
of
alleles
predicted
to
reduce
inbreed-
ing
depression
the
most.
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in
Ecology
&
Evolution
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x
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No.
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Monitoring
the
outcome
of
genetic
rescue
using
genomics
Once
genetic
rescue
has
been
implemented,
genomics
will
also
have
a
key
role
in
monitoring
the
outcome.
In
partic-
ular,
genomics
can
be
used
to
characterize
the
spread
of
immigrant
alleles
in
the
target
population,
determine
which
immigrants
contribute
the
most
to
population
growth,
and
determine