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AnnlL Rev. Genetics 1995. 29:305-27 Quick links to online content
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CONSERVATION GENETICS

R. Frankham
Key Centre for Biodiversity and Bioresources, Macquarie University, Sydney, New
South Wales 2109, Australia

KEY WORDS: extinction, endangered, genetic variation, inbreeding depression, genetic

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adaptation
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ABSTRACT

Inbreeding depression, accumulation and loss of deleterious mutations, loss of

genetic variation in small populations, genetic adaptation to captivity and its
effect on reintroduction success, and outbreeding depression are reviewed. The
impact of genetic factors in endangerment and extinction has been underesti­
mated in some recent publications. Inbreeding depression in wildlife and in the
field has been clearly established, while its impact has been greatly underesti­
mated. The size of populations where genetic factors become important is higher
than previously recognized, as NelN ratios average 0.11. Purging effects have
been overestimated as a mechanism for eliminating deleterious alleles in small
populations. The impact of loss of genetic variation in increasing the suscepti­
bility of populations to environmental stochasticity and catastrophes has gener­
ally been ignored. Consequently, extinctions are often attributed to "nongenetic"
factors when these may have interacted with genetic factors to cause extinction.

CONTENTS
INTRODUCTION.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
GENETICS IN CONS ERVATION BIOLOGy................................. 306
INBREEDING, GENETIC V ARIA T10N, AND EXTINCTION . . . . . . . . . .. .. . . .. .. 307
Inbreeding Depression in Wildlife. . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . .. .. . . .. .. 307
Inbreeding and Extinction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. . . .. .. 308
Low Genetic Diversity, Endangerment, and Extinction in Wildlife. . . . . .. .. . . .. .. 309
Alleviating Inbreeding Depression: Immigration. .. . . . . . . . . . . . . . . . . .. .. . . .. .. 310
ACCUMULATION AND LOSS O F DELETERIOUS MUTATIONS............... 310
GENETIC DETERIORATION I N CAPTIVITy................................ 313
GENETIC MANAGEMENT O F THREATENED POPULATIONS ... . . . . . . . . . . . . . 313
Maintenance of Genetic Variation .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
N ,/N i n Wildlife . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
HOW LARGE? ................................ ................... ....... 316
OUTBREEDING DEPRESS ION............................ ................ 317
ROLE O F LABORATORY ANIMALS....................................... 317
PERS PECTIVE...... ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
MAJOR ADVANCES 1 980-1995 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
FUTURE DIRECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320

305
 306 FRANKHAM

INTRODUCTION

The biological diversity of the planet is rapidly being depleted as a direct or

indirect consequence of human actions (166). An unknown but large number
of species are already extinct, while many others have reduced population sizes
that put them at risk. Many species now require human intervention to optimize
their management and ensure their survival. The scale of the problem is
enormous: 11.7% and 10.6% of mammals and birds, respectively, are catego­
rized as threatened by the World Conservation Union (IUCN) (101), while a
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recent assessment from the Conservation Breeding Specialist Group (CBS G)

of mCN classified 38% of 3559 vertebrate taxa as threatened, based on
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different criteria (135).

Four justifications for maintaining biodiversity have been advanced (14,
103, 123): the economic value of bioresources, ecosystem services, aesthetics,
and rights of living organisms to exist. mCN recognizes the need to conserve
biodiversity at three levels: genetic diversity, species diversity, and ecosystem
diversity. Genetics is directl y involved in the first two of these. The primary
factors contributing to extinction are habitat loss, introduced species, overex­
ploitation, and pollution (103, 123, 166). Typically these factors reduce species
to population sizes where the y are susceptible to stochastic effects, whether
environmental, catastrophic, demographic, or genetic (inbreeding depression,
loss of genetic variation, and accumulation of deleterious mutations). Although
there is little critical evidence on the stochastic factors in extinction, there is
much evidence that some of the problems are genetic (43, 48, 72, 95, 103,
123, 133, 143-146, 153, 166).

GENETICS IN CONSERVATION BIOLOGY

Sir OUo Frankel (138) was largely responsible for the recognition of genetic
factors in conservation biology. Since 1980, Michael Soule has had a profound
influence on the development of conservation biology as a multidisciplinary
crisis field drawing on ecology, genetics, and wildlife and resource biology
(48, 143-146).
There are seven major genetic issues in conservation biology: (a) inbreeding
depression, (b) accumulation and loss of deleterious mutations, (c) loss of
genetic variation in small popUlations, (d) genetic adaptation to captivity and
its effect on reintroduction success, (e) outbreeding depression, if) fragmenta­
tion of popUlations and reduction in migration, and (g) taxonomic uncertainties
and introgression.
This review focuses on the first five issues, with an emphasis on the con­
ceptual underpinning of the discipline, genetic management of captive popu­
lations, modeling problems using laboratory animals, and on outbreeding
 CONSERV ATION GENETICS 307

animals. Space constraints dictate that this review is selective, rather than
comprehensive, and that referencing is primarily to reviews and recent papers.
Other major issues are listed under Major Advances. The conservation of
livestock genetic diversity has been reviewed elsewhere (10,140):

INBREEDING, GENETIC VARIATION, AND EXTINCTION

The fundamental assumption underlying the application of genetics within

conservation biology is that inbreeding and loss of genetic variation increase
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the risk of extinction. Although this may seem self-evident to geneticists, other
biologists have expressed considerable skepticism about this and the general
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relevance of genetics to conservation biology (29,30,50).

Inbreeding Depression in Wildlife

Inbreeding depresses reproductive fitness in outbreeding domestic plants and
animals (42,169). Nevertheless, there was skepticism that wildlife suffered
from inbreeding depression. Ralls and Ballou and others have provided com­
pelling evidence that captive populations of vertebrate wildlife suffer from
inbreeding depression(36,82,83,126,127,129). For example, inbred indi­
viduals showed reduced juvenile survival compared to outbreds in 42 of 45
mammalian populations (127). The extent of inbreeding depression, measured
as lethal equivalents per zygote, averaged 4.6, with no clear indication of any
differences among mammalian orders (129). These data underestimate the full
effect of inbreeding depression as it is approximately three times greater for
total fitness than for its components (15,48).
The argument about inbreeding depression has now shifted to wildlife in
nature. Since inbreeding depression is typically more severe in harsher envi­
ronments (43, 72, 90, 106), it should be more severe in the wild than in
captivity. It has recently been claimed that there is no evidence that populations
in the wild suffer from inbreeding depression (29). However. this is fallacious.
Inbreeding depression in wild or serniwild environments has been reported in
several species of fish (153, 158), snails (32), lions (153), shrews (148),
white-footed mice (75),golden lion tamarins (AJ Baker & JM Dietz, in prepa­
ration), two species of birds (77; J Carrick & PR Brussard, personal commu­
nication), and several species of outbreeding plants (31,39,40,43,44,70,
76). For example, Vrijenhoek's group (158) showed that a genetically variable
sexual species of fish numerically dominated a related parthenogenetic species
until a drought eliminated their habitat. When the populations were sub­
sequently reestablished, the sexual species possessed reduced genetic variation
from a founding event and was consistently less abundant than the partheno­
genetic species. The sexual species reestablished its numerical dominance
 308 FRANKHAM

following the deliberate addition of genetic variation via replacement of 30

sexual individuals by fish from elsewhere. The failure of several studies in
birds to find inbreeding depression can be attributed to incorrect paternities
and biases in environmental quality that favor inbred matings (SO). The release
of captive-bred inbred and outbred offspring into the same habitats avoids both
these problems (32, 75). The occurrence of inbreeding depression in cheetahs
is controversial and has been the subject of much debate (29,30,105,117).
That controversy stems mainly from the lack of noninbred cheetahs to use as
controls. Inbreeding depression was greater in the wild than in captivity in five
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of six cases (32, 40, 75,76). Overall, there is clear and unequivocal evidence
of inbreeding depression in the wild.
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Inbreeding and Extinction

Inbreeding is presumed to increase the risk of extinction, since it depresses
components of reproductive fitness in naturally outbreeding species. This
presumption is supported by correlations between cumulative extinctions and
deliberate inbreeding in laboratory and domestic animals (142). However,
genetic and nongenetic causes of extinction were not delineated in the Soule
study. When nongenetic causes of extinction were removed, inbreeding mark­
edly increased rates of extinction in all animal species with relevant data (50).
All showed a threshold relationship between incremental extinction and in­
breeding, with low initial extinction, but sharply increased extinction rates
beginning at intermediate levels of inbreeding. There was no significant dif­
ference in extinction levels at similar inbreeding coefficients in populations
inbred at different rates (full-sib vs first cousin). Extinctions have also been
observed with extremely slow rates of inbreeding due to finite population size;
15/60 captive populations of Drosophila melanogaster with effective popula­
tion sizes of about 50 went extinct over 210 generations (90).
Inbreeding in wildlife occurs as a consequence of the cumulative effects of
finite population size, often over hundreds of generations. For naturally out­
breeding species, inbreeding can be estimated from loss of allozyme heterozy­
gosity (17, 22,42, 165; M Montgomery, R Nurthen, L Woodworth, D Briscoe
& R Frankham, unpublished data; see Equation 1 below). A substantial number
of wildlife populations have very low levels of allozyme heterozygosity (50,
112) (Table 1), indicating that they may have reached high levels of inbreeding.
Of 911 animal species in the compilation by Nevo et al (112), 4.7% had no
allozyme heterozygosity and 10.0% had less than 1%; the corresponding values
for mammals were even higher (9.8% and 16.8%). Inbreeding depression due
to finite population sizes has been found in one experimental and two wild
plant populations (70, 121) and in Drosophila (17, 22, 89, 165).
In the wild, demographic and environmental stochasticity and catastrophes
 CONSERV ATION GENETICS 309

contribute to extinction. It has been claimed that these factors are more im­
portant causes of extinction in wildlife than inbreeding (29, 30, 84). However,
the responses of populations to these factors are all affected by inbreeding and
loss of genetic variation, so that extinctions can be incorrectly attributed to
"nongenetic" factors rather than to interactions between genetic and "nonge­
netic" factors. Birth and death rates are susceptible to inbreeding depression
(31,42, 169), and sex-ratio distortions are sometimes found in inbred popula­
tions (146, 167). Loss of genetic variation decreases the ability of wild popu­
lations to survive climatic extremes, pollutants, diseases, pests, and parasites
(43, 50, 56a, 70, 72, 122, 158).
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Claims that populations are more likely to go extinct in the wild from
demographic and environmental stochasticity before inbreeding and loss of
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genetic variation become important(84) have been questioned by recent theo­

retical studies. Mills & Smouse (l08) showed that inbreeding is likely to
contribute to population decline, especially for species with low reproductive
rates. Other related theoretical studies have come to similar conclusions
(63,
65). These models ignore factors that both increase and decrease the impact
of inbreeding; all ignore the effects of inbreeding in purging deleterious alleles
(see below), and so overestimate the impact of inbreeding. Conversely, they
underestimate the impact of inbreeding for reasons that probably have greater
impact; the Mills & Smouse model ignores adult sterility (l08), a potentially
important cause of extinction (M Treadwell & R Frankham, unpublished data);
Halley & Manasse (63) assumed that effective population size equals actual
size, whereas it is about one ninth of this (see below); Hartt & Haefner (65)
used estimates of inbreeding depression for single fitness components in cap­
tivity that severely underestimate effects for total fitness in the wild.

Low Genetic Diversity, Endangerment, and Extinction in

Wildlife
Species with low genetic variation, such as seIfers, would be expected to have
reduced ability to cope with environmental change during evolution, and so
have shorter evolutionary lifespans. The taxonomic distribution of selfing and
asexual species of plants, terrestrial slugs, and marine invertebrates indicates
that they are more prone to extinction than outbreeders (50). Low genetic
variation is associated with increased susceptibility to diseases, pests and
parasites in domestic animals and plants, and weeds (43, 56a, 50, 113). The
evidence for such associations in wildlife is mostly correlative (116) and has
been criticized (29,30). However, loss of genetic variation led to increases in
parasite load in fish in the wild (158). While there is need for more evidence
in wildlife, the extensive support for this hypothesis from genetics, immunol­
ogy, and veterinary and human medicine makes it extremely improbable that
it does not apply to wildlife.
 310 FRANKHAM

When species become endangered as a consequence of long histories of

moderate effective population sizes and consequent inbreeding, they will have
low genetic variation. Conversely, when genetic factors are irrelevant and
populations decline rapidly from habitat loss, pollution, or overexploitation,
endangered species will have normal levels of genetic variation. A large and
highly significant excess (32 of 38 ) of endangered populations and species
have low levels of genetic variation compared to related nonendangered spe­
cies (Table 1). Whether inbreeding has reduced reproductive fitness and causes
endangennent or low population size associated with endangerment has re­
duced genetic variation is unclear. Even in the latter case, inbreeding depres­
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sion will exacerbate endangerment. Consequently, genetic concerns appear to

be of significance in the majority of endangered species and populations whose
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genetic variation has been measured.

Suggestive evidence for the role of inbreeding and loss of genetic variation
in decline and extinction of wild populations exists for Florida panthers, Puerto
Rican parrots, Isle Royale wolves, inbreeding colonial spiders, native mice
(Peromyscus polionotus), heath hens, bighorn sheep, and middle spotted wood­
peckers (24, 50). Further, the greater susceptibility to extinction of island than
mainland populations (123, 166) is expected on genetic grounds. Populations
on islands lose genetic variation at foundation (often a single pair), and through
subsequent low average population sizes; vertebrates on islands have less
genetic variation than mainland populations (112). Although the susceptibility
of island populations to extinction has been interpreted as being due to "nonge­
netic" causes, it is most probably due to the interactions of genetic and "nonge­
netic" factors.

Alleviating Inbreeding Depression: Immigration

The obvious way to overcome inbreeding depression in small populations is
to introduce immigrants from elsewhere. There is ample evidence that this
improves reproductive fitness (42,70,121,147,158,169),though occasionally
it results in outbreeding depression (see below).

ACCUMULATION AND LOSS OF DELETERIOUS

MUTATIONS

Deleterious mutations are added to populations by mutation and removed by

natural selection. However, some become fixed in small populations and
reduce reproductive fitness (85, 100). Lande (85) has predicted that the accu­
mulation of new mildly deleterious mutations in populations up to effective
sizes of 1000 or more may be a more important cause of extinction than
demographic stochasticity, and of similar importance to environmental sto-
 CONSERVATION GENETICS 311

Table 1 Levels of genetic variation i n endangered species and populations (reference)

Low Normal High

Mammals
Cheetah (116) Indian rhino (37) Speke's gazelle (28)
Greater panda (116) Humpback whale (7)
Asiatic lion (116)
Black-footed ferret (116)
Northern hairy-nosed wombat
(149)
Cotton top tamarin (33)
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Lion tamarin (116)

European bison (64)
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Arabian oryx (160, 164)

Ethiopian wolf (60)
White rhinoceros (104)
Pere David's deer (164)
Black rhinoceros (104)
Przewalski's house* (67)
Channel Island fox (161)
Florida panther (116)
Isle Royale gray wolf (162)
St Lawrence beluga whale
(119)
Sand gazelle* (61)
Birds
Hawaiian goose (131) Red cockaded woodpecker (103)
Spotted owl (13) Palila (46)
Whooping crane (96) California condor (34)
Puerto Rican parrot (24)
Kakapo (154)
Fish
Topminnow (158)
Insects
Uncompahgre fritillary butter­
fly (23)
Plants
Howellia aquaticus (123)
Pedicularis furbishiae (159)
Ptilimnium nodosum (78)
Amsinckia grandiflora (120)
Torreya taxifolia (134)
Trifolium stoloniferum (71)

*lntrogression
 31 2 FRANKHAM

chasticity. As these models are sensitive to assumptions regarding the magni­

tude and distribution of mutational effects, it is critical that they be evaluated
experimentally.
Rare recessive deleterious mutations are exposed by inbreeding and so can
be more effectively removed from inbred than outbred populations through
natural selection. Such purging has been documented in selfing plants, mice,
birds, and Drosophila, and in the many species where highly inbred lines have
been developed (1, I I, 27,42,50,90,98, 132, 169).
In contrast, several recent studies have questioned the extent of purging.
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Theoretical investigations show that mildly deleterious alleles are not effec­
tively purged (31, 68). In Drosophila, mildly deleterious and lethal mutations
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contribute equally to inbreeding depression (31). Selfing plants have been

shown to suffer from inbreeding depression (2, 12, 31, 39). No relationship
between inbreeding depression and conditions expected to lead to purging has
been found in native mice and some plant populations (16, 20, 66). Artificial
selection for reproductive fitness during seven generations of full-sib inbreed­
ing in D. melanogaster failed to prevent 88% inbreeding depression (55).
Significant evidence for purging was found in only 1 of 19 wildlife species,
though there was a trend in the direction predicted by purging in 15 of 19
cases (J Ballou, personal communication). In no species did purging eliminate
statistically significant inbreeding effects. Purging may ameliorate inbreeding
depression, but it is most unlikely to eliminate it.
Captive populations of endangered species are often founded from small
numbers such that inbreeding becomes unavoidable (69). Templeton & Read
(150, 151) devised a scheme to eliminate inbreeding depression in such popula­
tions. This involved increasing population size, equalizing founder repre­
sentation, choosing healthy inbred individuals as parents, and dissortative
mating with respect to pedigree. When the scheme was implemented in Speke's
gazelle, they reported a significant reduction in inbreeding depression after only
two to three generations. This has been widely interpreted as a program to purge
populations of their deleterious alleles, but Templeton & Read (152) attribute the
benefits to selection of a favorable epistatic combination. Several doubts have
been raised regarding the effectiveness of this program (68, 163, 168). The
changes may have been caused by environmental changes over time. The
original animals were born elsewhere, and as the herd grew, it was dispersed to
other zoos in Texas where the climate is different from that of the original
location in St Louis. Further, the correction used to allow analyses of zero
survival values may have introduced a bias (82, 163): The significance of the
difference was removed when an alternative correction was used. Experimental
evaluations of components of the Templeton & Read procedures have not
yielded worthwhile reductions in inbreeding depression (94, 168),but the total
program has yet to be evaluated in a controlled, replicated experiment.
 CONSERVATION GENETICS 313

GENETIC DETERIORATION IN CAPTIVITY

Captive breeding is being used as a means of saving endangered species from

extinction, with reintroduction into the wild usually being the desired end point
(127, 128). Three adverse genetic changes occur in captivity: inbreeding de­
pression (see above), loss of genetic variation (see below), and genetic adap­
tation to the captive environment. Selection for tameness and other adaptations
to the captive environment are likely to jeopardize reintroduction success.
Genetic adaptation to captivity has been documented in fish, plants, bacteria,
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and several Drosophila species (52, 54, 79, 89, 93). It is generally disadvan­
tageous on return to the natural environment (52, 79). Considerable difficulty
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has been encountered in the reintroduction of endangered vertebrate species

into the wild (136). Genetic adaptation to captivity is one of many possible
reasons for this, but there is no critical evidence to separate this from other
possible causes.
It is important to minimize genetic adaptation to captivity for populations
likely to be used for reintroduction into the wild. This should occur when
generations in captivity, selection in captivity, and heritability of reproductive
fitness in the captive environment are minimized, and when generation length
and the proportion of immigrants are maximized (4, 52, 54, 87). Equalizing
family sizes should reduce genetic adaptation by approximately 50% as it
removes the among-family component of selection. However, it was not suf­
ficient to prevent severe genetic deterioration when captive populations of D.
melanogaster maintained for 50 generations under uncrowded conditions were
measured under competitive "wild" conditions (L Woodworth, M Mont­
gomery, D Briscoe & R Frankham, unpublished data). It is unclear whether
this genetic deterioration was due to genetic adaptation to captivity or to the
accumulations of new deleterious mutations.

GENETIC MANAGEMENT OF THREATENED

POPULATIONS

It is clearly desirable to minimize inbreeding and loss of genetic variation in

the genetic management of threatened species. Most authors assume that het­
erozygosity represents evolutionary potential (42). though others have stressed
the need to retain allelic diversity (3, 57). Although allelic diversity and
heterozygosity are frequently related (17. 22. 112. 165),heterozygosity is less
affected by severe population size bottlenecks than allelic diversity.
Maintenance of Genetic Variation
The expected proportion of neutral genetic variation (heterozygosity HI) re­
tained within a population after t generations is given by Equation 1 (42):
 314 FRANKHAM

H,IHo = [1 - lI(2Ne)]' = 1 - F, 1.

where Ho = initial heterozygosity, Ne

number of generations, and F = the inbreeding coefficient. Consequently,
retention of heterozygosity is maximized by (a) maximizing initial heterozy­
gosity, (b) maximizing generation interval (minimizing number of genera­
tions), and (c) maximizing effective population size. As population size (N=
number of sexually mature adults), rather than Ne
N/Nratio should both be maximized. Each of these predicted effects is con­
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sidered in turn below.

For most populations in nature, little can be done to modify initial heterozy­
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gosity, though immigration may sometimes be possible. For captive popula­

tions, initial heterozygosity can be maximized by initiating populations with
at least 20-30 unrelated founders (127, 128) and by ensuring that the sampling
of the gene pool is representative. James (74) predicted that a population size
bottleneck of N individuals would reduce heterozygosity and evolutionary
potential by lI2Ne, providing the popUlation size recovered in one generation.
Bottlenecks have been shown to reduce allozyme variation (12, 64, 91). Five
experimental evaluations of this theory for quantitative characters, four using
bristle characters in Drosophila and one using wing characters in butterflies,
have validated James' predictions (18, 49). Conversely, Bryant et al (26)
reported results from houseflies that conflicted with predictions; the bottle­
necked lines showed elevated genetic variation for characters that exhibited
nonadditive genetic variation, as indicated by inbreeding depression. Further,
Lopez-Fanjul & Villaverde (97) showed elevated selection response for a
fitness character in bottlenecked lines of Drosophila. However, the relevance
of their results to conservation remains obscure, as bottlenecked populations
suffer reduced reproductive performance, and their long-term evolutionary
potential is likely to be impaired.
Many captive populations of wildlife have been founded when only small
numbers are left (69). For example, the captive population of Speke's gazelle
in the U.S. was founded from one male and three females. These founders
often contribute unequally, such that the rate of inbreeding and the loss of
genetic variation is increased. Consequently, it has been recommended that
such populations be managed to equalize founder representation. This proce­
dure reduced inbreeding and improved retention of genetic variation, but
produced no benefits in reproductive fitness when evaluated in Drosophila
(94).
Generation interval can be maximized by cryopreservation (109) or by
breeding from older animals. Embryo freezing technology is used in conser­
vation of domestic mammals (140) and for stock maintenance in mice, but is
not available for most wildlife. Semen freezing is used in conservation of
 CONSERVATION GENETICS 315

domestic mammals and birds, but is not available for most wildlife. For the
majority of nondomesticated species, breeding from older animals is currently
the only means for extending the generation interval, and that may be difficult
to achieve.
Large populations retain more genetic variation on average than small popu­
lations. Allozyme heterozygosity in D. melanogaster declined as predicted by
Equation 1 in pedigreed populations with effective sizes of 25-500 over 50
generations (M Montgomery, L Woodworth, R Nurthen, D Briscoe & R
Frankham, unpublished data). Positive correlations between allozyme variabil­
Annu. Rev. Genet. 1995.29:305-327. Downloaded from www.annualreviews.org

ity and log N within species have been reported for 13 of 14 wildlife species
studied (41, 123-125, 156). Further, allozyme heterozygosity showed a corre­
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lation of 0.7 with log N across animal species (141). Loss of quantitative
genetic variation was greater with smaller Ne, and increased with generations,
as predicted by Equation 1 (21, 51). Further, selection response for quantitative
characters was greater in larger than smaller populations in six studies involv­
ing Drosophila, mice, m aize, and chickens (49, 137, 157).
The genetic consequences of finite population size are predicted to depend
on the effective population size rather than the census size (42). Ne is predicted
to depend not only on the number of sexually mature adults, but on variation
in family size, inequalities in sex ratio, on fluctuation in numbers over gen­
erations, and on selection. While this simple single-locus neutralist theory has
been widely used, most of its predictions had not been subjected to experi­
mental evaluation until recently.
Equalization of family size (EFS) is predicted to double Ne and so reduce
loss of genetic variation, inbreeding, and inbreeding depression in comparison
to variable family sizes (VFS) (42). Consequently, EFS has been recommended
in the captive breeding of rare breeds and endangered species (48, 87, 127,
128, 143, 144, 146). EFS led to greater Ne, retention of allozyme variation,
quantitative genetic variation and reproductive fitness, and slower inbreeding
than VFS, as predicted, in a controlled, replicated study of this procedure in
Drosophila (17, 51). Similar, but less extensive results have been obtained in
Tribolium, mice, and Japanese quail (15, 49).
Polygamous mating systems are predicted to reduce the effective population
size and so increase the rate of inbreeding and loss of genetic variation. Our
studies (22) conftrmed these predictions. Consequently, harem breeding struc­
tures should be avoided, or circumvented, as far as possible in programs for
conservation of wildlife.
Fluctuations in population size are common in natural populations of animals.
They are predicted to reduce the effective population size to approximately the
harmonic mean size, and so increase the rate of inbreeding and loss of genetic
variation. These predictions have been experimentally validated (165). Such
fluctuation should be minimized in wildlife conservation programs.
 316 FRANKHAM

Ballou & Lacy (9) have predicted that minimizing kinship is the optimum
means for managing small pedigreed populations with unequal founder con­
tributions to maximize retention of heterozygosity and allelic diversity. This
procedure combines the benefits of equalizing family sizes and adjusting
founder representation. It is being applied to endangered species management,
but has yet to be experimentally evaluated.

Nem in Wildlife
Widely divergent views have been expressed about the magnitude of NJN in
Annu. Rev. Genet. 1995.29:305-327. Downloaded from www.annualreviews.org

wildlife. Empirical estimates were reported to be 0.5�.8 (42), or 0.2�.5 (102),

while values of 0.05 and less have been reported (21, 123). Nunney (114)
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predicted that special conditions were required for the ratio to be less than 0.5,
whereas Nunney & Campbell (115) suggested that it would usually be greater
than 0.25, though it could be less than this if population size fluctuated
significantly. Empirical estimates that include the effects of unequal sex-r�tio,
variance in family sizes and fluctuations in population size average 0.11, much
lower than generally assumed (53). Most estimates are biased upward as they
do not include the effects of fluctuations in population size (53, 73).
Genetic management can potentially increase the effective size of popula­
tions by almost 20-fold, given that estimates of N/N average 0.11 in unman­
aged populations, while an Ne of approximately double N is achievable by
management that equalizes family sizes, sex-ratios and numbers in different
generations. In D. melanogaster, a 40-fold difference in N/N ratio exists
between large unmanaged cage populations and populations subject to recom­
mended genetic management (17, 21).

HOW LARGE?
How large do populations have to be to (a) avoid inbreeding depression, and
(b) retain their evolutionary potential? It is widely asserted that an Ne of 50 is
sufficient to avoid inbreeding depression in the short term (56, 142). This figure
may simply be an artifact of the size of data sets, as it is based largely on the
experience of animal breeders. Recently, Latter & Mulley (89) found inbreed­
ing depression in long-term populations with effective sizes of approximately
50. Inbreeding depression was proportional to the inbreeding coefficient in
pedigreed populations maintained for 50 generations with effective sizes be­
tween 25 and 500 (L Woodworth, M Montgomery, D Briscoe & R Frankham,
in preparation). No finite population appears to be immune from inbreeding
depression in the long term.
Franklin (56) suggested that an Ne of 500 should be sufficient for indefinite
retention of evolutionary potential due to a balance between drift and mutation.
He argued that evolutionary potential was determined by quantitative genetic
variation rather than single-locus variation, and heterozygosity rather than
 CONSERVATION GENETICS 317

allelic diversity. A similar Ne was suggested for a model incorporating stabi­

lizing selection (88). Estimates of the mutation rate for different quantitative
characters in several species approximate that used by Franklin (86, 99). As
mutations are predominantly deleterious, the total mutation rate will not be the
appropriate value. After adjusting the rate by omitting severely deleterious
mutations, Lande (86) suggested that an Ne of 5000 is required to retain
evolutionary potential for reproductive fitness. Preliminary data from D. mel­
anogaster suggest that an Ne in the hundreds, rather than thousands, is required
(E Lowe, L Woodworth, M Montgomery, D Briscoe & R Frankham, unpub­
Annu. Rev. Genet. 1995.29:305-327. Downloaded from www.annualreviews.org

lished data).
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OUTBREEDING DEPRESSION

Reproductive fitness may be reduced following hybridization of populations

within species, either in the FJ or in later generations. Such outbreeding
depression is associated with local adaptation (coadapted gene complexes) and
low vagility, and may be common in plants (12, 41,153). However, larger and
more vagile animals show less local adaptation, so it is expected to be rarer
in them. The ibex in Slovakia is quoted as showing outbreeding depression
(155), but the validity of that claim is rather dubious as no quantitative data
were presented. Outbreeding depression was nonsignificant in Speke's gazelle,
orangutans, D. subobscura, human interracial marriages, and subspecies
crosses in Peromyscus polionotus (38, 81, 151; J Ballou, personal communi­
cation). Significant effects were found in Goeldi's monkey, Caucasians, D.
pseudoobscura, D.willistoni, one fish, one amphibian, and two marine inver­
tebrates (19, 38,82,153). In most cases outbreeding depression was modest.
In Goeldi's monkey it was only one tenth the magnitude of inbreeding depres­
sion and may have been an artifact due to wild-caught animals being better
than captives at rearing offspring in captivity (82). In D. pseudoobscura and
D. willistoni, interpopulation F2s showed reductions of 6-17% in fitness com­
ponents compared to within-population flies (38). Even Fls and F2s of crosses
between species often exhibit little or no decline, or even increases, in fitness
(5). Outbreeding depression is most common where genetic divergence is
strong and the taxonomic status of popUlations is in question. More quantitative
data are needed on the frequency of outbreeding depression, its severity, and
the situations where it is found. However, it is clearly less important in animals
than inbreeding depression.

ROLE OF LABORATORY ANIMALS

Substantial conceptual advances in conservation genetics have come from the

use of laboratory species. Endangered species are unsuitable for controlled,
replicated evaluations of relevant theories. They are typically slow breeders,
 318 FRANKHAM

expensive to maintain,available in low numbers, and too valuable to risk in

experimentation. Studies to evaluate such theory can most efficiently and
appropriately be done using a convenient laboratory animal (51).
Drosophila, mice,and Tribolium have proven to be valid models for inves­
tigating a wide range of related issues in population genetics, quantitative
genetics, animal breeding, and conservation genetics (42, 51,130, 169). Sur­
prisingly, the use of laboratory animals in conservation genetics is recent (47).
Extensive studies using Drosophila have been carried out by our group and
by Hedrick's group (17,21,22,50,54,94,106,107,147,165,168), while
Annu. Rev. Genet. 1995.29:305-327. Downloaded from www.annualreviews.org

butterflies have been used by Brakefield's group (18),Tribolium by Pray et al

(122), and mosquitofish by LeBerg (91,92). Vrijenhoek and colleagues (158)
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have used fish in elegant combined field/experimental/laboratory work,while

Lacy and colleagues have used Peromyscus in a similar manner (20,75,81).

PERSPECTIVE

In some recent publications, genetic factors have been relegated to a minor

role in endangerment and extinction of wildlife in nature (29,30,84). However,
the evidence reviewed above clearly indicates that the impact of genetic factors
has been underestimated in these assessments. Inbreeding depression in wild­
life in the field has been clearly established. Estimates of the magnitude of
inbreeding depression in wildlife have greatly underestimated its impact as
they are based primarily on individual fitness components in captive popula­
tions. Inbreeding depression is about three times greater for total fitness than
for individual components,and about 40% greater in nature than in captivity.
The size of populations where genetic factors become important is higher than
previously recognized, as N/N ratios are much lower than previously sus­
pected. Purging effects have been overestimated as a mechanism for eliminat­
ing deleterious alleles in small populations. The impact of loss of genetic
variation in increasing the susceptibility of popUlations to environmental sto­
chasticity and catastrophes has generally been ignored. The impact of inbreed­
ing depression on birth and death rates and sex-ratio is typically ignored.
Recent theoretical investigations indicate that the impact of inbreeding on the
decline of wildlife popUlations has been underestimated. Consequently, ex­
tinctions are often attributed to "nongenetic" factors when these may have
interacted with genetic factors to cause extinction.
Familiarity with the wider literature from domestic and laboratory species
seems to be a major factor in the different perceptions of geneticists and others
in controversies over genetic factors in conservation. Since the genetic behav­
ior of domestic and laboratory species is similar to that of wildlife popUlations,
they provide an invaluable perspective to the limited data available for wildlife
that should not be ignored.
 CONSERVATION GENETICS 319

MAJOR ADVANCES 1980-1995

Major conceptual and practical advances in conservation genetics since its

inception in the early 1980s are listed below.

• Population and quantitative genetic principles have been introduced into the
management of threatened species, especially in captivity. CBSG has
played a major global role in this.
• Inbreeding depression has been demonstrated in wildlife, both in captivity
and in the wild.
Annu. Rev. Genet. 1995.29:305-327. Downloaded from www.annualreviews.org

• Inbreeding has been shown to cause extinctions in laboratory animals.

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• Many endangered species have been found to have low levels of genetic
variation.
• NJN ratios in wildlife have been shown to be much lower than previously
suspected.
• The predicted effects on Ne of variation in family size, sex-ratio distortion,
and fluctuations in numbers over generations have been verified.
• Equalizing founder representation has been shown to reduce inbreeding and
loss of genetic variation.
• Minimizing kinship has been predicted to be the optimum means for man­
aging small pedigreed populations with unequal founder contribution.
• Introduction of unrelated individuals has been shown to improve the repro­
ductive fitness of partially inbred populations.
• Inbreeding depression has been shown to be monotonically related to the
inbreeding coefficient, so that no finite population is immune from it.
• Theoretical studies have predicted that an Ne of 500-5000 is required for
populations to retain their evolutionary potential.
• Accumulation of mildly deleterious mutations has been predicted to pose a
serious extinction risk in finite populations.
• Inbreeding depression has been shown to increase the risk of extinction in
demographic models.
• Progress has been made in delineating the genetic consequences of partially
isolated fragmented popUlations (meta-populations) (see Reference 59).
• Genetic adaptation to captivity has been documented and shown to reduce
reintroduction success.
• Purging of deleterious mutation has been shown to be only partially effective.
• Laboratory animals have been used to evaluate theory and to investigate
problems in conservation genetics.
• Mace & Lande (102) proposed that endangerment be defined as the prob­
ability of extinction within a given time frame. They provided simple
guidelines to do this, based on population biology principles.
 320 FRANKHAM

• Population viability assessment (PVA) procedures have been developed to

predict the probability of extinction from the combined effects of all factors
impacting on populations, and software packages have been developed for
this (see Reference 80).
• Genetic markers have been used to resolve taxonomic uncertainties, and to
define effective conservation units (6, Il l , 116, 160).
• Polymerase chain reaction (PCR) has provided nondestructive means for
genotyping endangered species (110). Animals can be monitored from
hairs, feathers, museum specimens, or excrement, birds can be sexed, and
Annu. Rev. Genet. 1995.29:305-327. Downloaded from www.annualreviews.org

diet can even be determined.

Highly variable microsatellite DNA markers have been discovered and
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applied to conservation problems (25). They are highly informative and

will be widely used in conservation genetics.
• Genetic monitoring has been used to identify genetically distinct populations
for augmentation of small inbred populations to alleviate inbreeding and
increase genetic variation (28, 116).
• Genetic monitoring of wild populations has been used to identify the best
populations for reintroductions (158).
• Genetic markers have been used to infer the relationship among founders in
popUlations of endangered species, so their genetic management can be
optimized (58, 62).
• Genetic monitoring has been used to detect introgression (60, 116).
• Genetic markers have been used to determine paternity in studies of the basic
biology of endangered species (6, 110).
• Molecular genetic markers have been used to detect illegal hunting (6, 8).
• The use of genetic distances has been advocated for setting conservation
priorities according to taxonomic distinctness (35).

FUTURE DIRECTIONS

The following are major questions in conservation genetics that should be

addressed in the immediate future.

• How large is inbreeding depression for total reproductive fitness in the wild?
• How does it differ among species?
• Can the susceptibility of popUlations to inbreeding depression be predicted?
• Does NelN differ in wildlife species with different life history characteristics?
• How large do populations need to be to retain their evolutionary potential?
• What are the genetic consequences of meta-populations?
• What determines evolutionary potential; allelic diversity or heterozygosity?
 CONSERVATION GENETICS 321

• What best predicts the ability of populations to evolve: allozymes, microsatel­

lites, fluctuating asymmetry, quantitative genetic variation, or inbreeding
coefficients?
• Does minimizing kinship provide the best means for genetically managing
captive populations?
• How accurately can PVA software predict extinction probabilities?
• How great is the threat of wildlife extinctions from accumulation of new
deleterious mutations?
How important is outbreeding depression in animals?
Annu. Rev. Genet. 1995.29:305-327. Downloaded from www.annualreviews.org

• Does loss of genetic variation increase the susceptibility of wildlife to

diseases, pests and parasites in wildlife?
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• What is the relative importance of genetic factors, environmental stochas­

ticity, catastrophes and demographic stochasticity in causing extinction?
• How do their effects interact?

ACKNOWLEDGMENTS
I thank K Ralls and J Ballou for introducing me to conservation genetics and
J Ballou, J Barker, A Beattie, J Bell, D Briscoe, H Britten, P Brussard, B
Charlesworth, D Charlesworth, J Crow, M Eldridge, P England, N Flesness,
M Gilpin, P Hedrick, A Hoffmann, R Lacy, R Lande, B Latter, A Lindsay, V
Loeschcke, E Lowe, S Margan, C Moritz, R May, M Montgomery, S O'Brien,
K Ralls, M Soule, P Sunnucks, A Templeton, R Vrijenhoek, D Woodruff, and
L Woodworth for comments on the manuscript, and for information. My
greatest debt is to my collaborators D Briscoe, R Nurthen and our students
and staff. Research in my laboratory would not have been possible without
them. Our research is supported by Australian Research Council and Mac­
quarie University research grants, Publications 176 of the Research Unit for
Biodiversity and Bioresources.

Any Annual Review chapter, as well as an y article cited in an Annual Review chapter,
may he purchased (rom the Annual Reviews Preprints and Reprints service.
1-800-347-8007; 41 5-259-5017; email: arpr@c1ass.org

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