Ann. Zool. Fennici 40: 155–168 ISSN 0003-455X Helsinki 30 April 2003 © Finnish Zoological and Botanical Publishing Board 2003

Genetic threats to population persistence

Oscar E. Gaggiotti

Metapopulation Research Group, Department of Ecology and Systematics, P.O. Box 65, FIN-00014 University of Helsinki, Finland (e-mail: oscar.gaggiotti@helsinki.fi )

Received 27 Nov. 2002, revised version received 20 Jan. 2003, accepted 20 Jan. 2003

Gaggiotti, O. E. 2003: Genetic threats to population persistence. — Ann. Zool. Fennici 40: 155–168.

Human activities are having a devastating effect on the survival of natural popula- tions. The reduction in population size and changes in the connectivity of populations due to human disturbances enhance the effect of demographic and genetic factors that can lead to population . This article provides an overview of our current understanding of the role of genetic factors in the extinction of populations. The three primary genetic factors are loss of genetic variability, inbreeding depression, and accu- mulation of mildly deleterious . The effects of these factors are discussed in the context of three different scenarios: isolated populations, local populations with immigration, and metapopulations.

Introduction demographic and genetic factors (Lande 1988). However, the last decade has witnessed much Although the extinction of populations is a natu- progress in this area and there is a general agree- ral phenomenon, human induced habitat loss, ment that, although the most immediate causes pollution and have increased of extinction are human predation, introduction extinction rates well above background levels of exotic species and habitat loss, genetic factors and have lead to the mass extinction that we are can still play an important role. experiencing at the moment (Jablonski 1986, The purpose of this article is to provide an Woodruff 2001). An increased awareness of the overview of our current understanding of the consequences of human activities on the fate of role of genetic factors in the extinction of popu- natural populations has brought about a strong lations. I begin by addressing the case of isolated interest in the study of the ecological and genetic populations, which is applicable to species that factors that underlie population . A have been reduced to a few small and isolated decade ago or so, genetic factors received most populations or that are being maintained in cap- of the attention leading to a neglect of basic tivity. I then consider to what extent migration demography (Lande 1988). This bias lead to a can infl uence the effect of genetic factors on protracted controversy (Lande 1988, Caro & population persistence. A clear understanding of Laurenson 1994, Caughley 1994, Lande 1995) this problem is necessary to devise sensible man- over the relative importance of these two factors agement strategies aimed at maximizing popula- in the extinction of populations. The main imped- tion persistence. Finally, I describe the operation iment to the resolution of this controversy was of genetic factors in a metapopulation context. a poor understanding of the interaction between This scenario is applicable to species that have 156 Gaggiotti • ANN. ZOOL. FENNICI Vol. 40 been less affected by human disturbance and & Miller 1992). The types of genetic variation that are still represented by many interconnected considered most often are the heterozygosity subpopulations. of neutral markers, H, and the additive genetic

variance, Va, that underlies polygenic characters such as life-history traits, morphology, physiol- Population extinction ogy, etc. In small populations, random Natural populations are subject to extinction causes stochastic changes in gene frequencies, due to genetic factors even in the absence of due to Mendelian segregation and variation in human intervention. Genetic threats are a func- family size. In the absence of factors that replen- tion of the so-called effective population size, ish genetic variance such as , migration

Ne. Strictly speaking, Ne is defi ned as the number or selection favouring heterozygotes, popula- of individuals in an ideal population that would tions lose genetic variance according to give the same rate of random genetic drift as in the actual population (Wright 1931, Wright , (1) 1938). The ideal population consists of N indi- viduals with non-overlapping generations that where Va(t) is the additive genetic variance in reproduce by random union of gametes. More the tth generation (e.g. Hedrick & Miller 1992). intuitively, Ne can be defi ned as the number of A similar equation is obtained for heterozygos- individuals in a population that contribute genes ity by replacing Va with H. Genetic variation is to the following generation. This number can greatly reduced when populations are reduced to be much lower than the observed population a small effective size, Ne, and maintained at that size because of unequal sex ratios, variance in size for several generations. In fact, most genetic family size, temporal fl uctuations in population variation would be lost within about 2Ne genera- size, etc. (Frankham 1995). Thus, apparently tions (Wright 1969). Genetic variability can be large populations may still be facing genetic replenished to its original level through mutation problems. Small Ne can have multiple effects if the population grows back to its original size. that include loss of genetic variability, inbreed- The number of generations required for attaining ing depression, and accumulation of deleteri- the original level is of the order of the recipro- ous mutations. The time scales at which these cal of the mutation rate, m. Thus, for a nuclear factors operate differ and determine to a large marker with a mutation rate of 10–6, genetic extent the risk of population extinction that they variation is restored after 106 generations but entail (Table 1). the genetic variation of quantitative characters is restored after only 1000 generations because their mutation rate is two orders of magnitude Loss of genetic variability higher. The maximum fraction of genetic varia- Genetic variation is the essential material that tion lost during a bottleneck is a function of allows natural populations to adapt to changes the population growth rate (Nei et al. 1975). in the environment, to expand their ranges, and Populations that recover quickly after the bot- to reestablish after local extinctions (Hedrick tleneck lose little genetic variation even if the population was reduced to few individuals. For example, a growth rate of r = 0.5 (l = er = 1.65) Table 1. Time scale at which genetic factors operate allows a population that is reduced to only two and their importance for population extinction. individuals to retain 50% of its genetic vari- Factor Time scale Extinction risk ability (Fig. 1). If the population is reduced to 10 individuals, then a growth rate of r = 0.1 Loss of genetic diversity Long Low (l = 1.10) will allow it to retain 60% of its vari- Inbreeding depression Short High ability. Additionally, generation overlap can Mutational meltdown Medium/Long Unknown buffer the effect of environmental fl uctuations ANN. ZOOL. FENNICI Vol. 40 • Genetic threats to population persistence 157

1 on population sizes. In general, reductions in N = 2 0.9 population size are brought about by environ- 0.8 N = 10 mental changes that introduce fl uctuations in 0.7 vital rate parameters (e.g. survival, fecundity). 0.6 The effect of these fl uctuations on N depends 0.5 e 0.4 on the life history of each species. The ratio of Fraction lost 0.3 Ne to census size is directly proportional to the 0.2 total reproductive value of a population but the 0.1 sensitivity of this ratio to environmental fl uctua- 0 tions is proportional to the generation overlap 0.1 0.15 0.2 0.25 0.5 1 Growth rate, r (Gaggiotti & Vetter 1999). The larger the gen- eration overlap, the smaller is the effect of envi- Fig. 1. Fraction of the heterozygosity lost during a ronmental fl uctuations on the level of genetic population bottleneck that reduces population size to N = 2, 10 individuals. Calculated with eq. 8 in Nei et variability maintained by natural populations. al. (1975). Genetic variability is maintained through the “storage” of genotypes in long-lived stages. Adult individuals in these stages reproduce (Nei et al. 1975). This is of particular concern many times throughout their lives and, there- because the long-term response of a population fore, the genetic variability present in a given to selection is determined by the allelic diver- cohort is more likely to be transferred to future sity that remains after the bottleneck or that generations than in the case of organisms with is gained through mutations (James 1971). A discrete generations. second caveat is that in the case of quantitative These buffering mechanisms may explain genetic characters, genetic variability may not be why there are very few clear examples of popu- always benefi cial. Using an overlapping genera- lations that have lost a very large fraction of their tion model assuming weak stabilizing selection, genetic variability due to a bottleneck. One of Lande and Shannon (1996) showed that the the few cases is that of the Mauritius kestrel, effects of additive genetic variance on the aver- which was reduced to a single pair in the 1950s. age deviation of the mean phenotype from the A comparison of microsatellite diversity present optimum, and the corresponding “evolutionary” in museum specimens collected before the bot- load depends on the pattern of environmental tleneck and that present in extant individuals change. In an unpredictable (random) environ- reveals that at least 50% of the heterozygosity ment, additive genetic variance contributes to the was lost due to the bottleneck (Groombridge evolutionary load because any response to selec- et al. 2000). Another example is the northern tion increases the expected deviation between elephant seal, which was heavily exploited the mean phenotype and the optimum. However, during the nineteenth century and reduced to a when environmental changes are unidirectional, bottleneck population size estimated to be 10–30 cyclic, or positively correlated (predictable), individuals (Hoelzel et al. 2002). A comparison additive genetic variance allows the mean phe- of genetic diversity in prebottleneck and post- notype to track the optimum more closely, reduc- bottleneck samples shows a 50% reduction in ing the evolutionary load. mtDNA-haplotype diversity. The reduction in Most of the empirical studies of the effects heterozygosity at microsatellite loci, however, of population bottlenecks on genetic diversity was less pronounced. focus on heterozygosity of neutral markers. An important caveat concerning the effect Although neutral genetic variation may become of population size reductions on genetic diver- adaptive if the environment changes, the ability sity is that although they may not have a very of a population to respond to novel selective large effect on H, they will indeed have a large pressures is proportional to the additive genetic impact on allelic diversity (the mean number of variation underlying the traits that are the target alleles per locus) because random genetic drift of selection (Falconer & Mackay 1996). Unfor- will eliminate low frequency alleles very rapidly tunately, direct quantifi cation of the genetic 158 Gaggiotti • ANN. ZOOL. FENNICI Vol. 40 variation underlying polygenic traits is diffi cult In general, it is possible to conclude that loss and, therefore, heterozygosity of nuclear mark- of genetic variation, as measured by heterozy- ers is used as an indicator of additive genetic gosity and additive genetic, variance represents variation (Pfrender et al. 2001). This practice a long-term extinction threat. However, the loss is unwarranted because of the different rates at of allelic diversity can have important conse- which genetic variation is replenished in neutral quences in the short-term if it occurs at loci asso- and quantitative markers (Lande 1988). Indeed, ciated with disease resistance. a recent study (Pfrender et al. 2001) detected no signifi cant relationship between heritability and heterozygosity in natural populations of Daph- Inbreeding depression nia pulex and D. pulicaria. Thus, the absence of genetic diversity in nuclear markers may The decrease in fi tness due to mating between not necessarily indicate an immediate genetic related individuals is known as inbreeding threat. depression, and results from the presence of par- In general, the loss of genetic variation is tially recessive deleterious mutations maintained detrimental for the long-term survival of popu- by the balance between selection and muta- lations. However, as pointed out by Allendorf tion. Deleterious mutations occur continuously and Ryman (2002) there is one case where a in a population and most are at least partially reduction in genetic variability can represent an recessive. In large populations, selection keeps imminent extinction threat. This is indeed the these detrimental mutations at low equilibrium case for loci associated with disease resistance frequencies. Thus, under random mating, most such as the major histocompatibility complex copies of detrimental alleles are present in het- (MHC), which is one of the most important erozygous state and their detrimental effects genetic systems for infectious disease resist- are partially masked. Mating between relatives, ance in vertebrates (Hedrick & Kim 2000). however, increases homozygosity and, therefore, Allelic diversity at these loci is extremely high; the deleterious effects become fully expressed, for example, Parham (1996), and Parham and decreasing the fi tness of inbred individuals. Ohta (1996) documented 179 alleles at the MHC Although it is generally agreed that increased class I locus in humans. However, species that expression of deleterious partially recessive have been through known bottlenecks have very alleles is the main cause of inbreeding depres- low amounts of MCH variation. A study of the sion, there is an additional mechanism that Arabian oryx found only three alleles present at can contribute to inbreeding depression. If the the MHC class II DRB locus in samples from fi tness of a heterozygote is superior to that of 57 individuals (Hedrick et al. 2000). Hunting both homozygotes (heterozygous advantage pressure lead to the extinction of this species in or overdominance), the reduced frequency of the wild in 1972 and captive populations were heterozygotes will reduce the opportunities to susceptible to tuberculosis and foot-and-mouth express this overdominance. This mechanism disease, which is consistent with low genetic may be important for certain traits (e.g. sperm variability at MHC loci. Low genetic diversity precedence in Drosophila melanogaster), and at the MHC complex was also observed in bison, may contribute to the very high inbreeding which went through a bottleneck at the end of depression for net fi tness observed in Drosophila the 19th century (Mikko et al. 1997). In the and outcrossing plants (Charlesworth & Charles- Przewalskiʼs horse, in which the entire species worth 1999). is descended from 13 founders, Hedrick et al. The degree of inbreeding in a population (1999) observed four alleles at one locus and two is measured by the inbreeding coeffi cient F, alleles at a second locus. The northern elephant which can be defi ned as the probability that the seal is another example of low MHC diversity, two alleles of a gene in an individual are iden- Hoelzel et al. (1999) found only two alleles at tical by descent. The effect of inbreeding in a the MHC class II DQB gene in a sample of 69 population with inbreeding coeffi cient F can be individuals. measured in terms of the logarithm of the ratio ANN. ZOOL. FENNICI Vol. 40 • Genetic threats to population persistence 159

of the mean fi tness values for the outbred, WO, time as documented by Charlesworth and Char- and the inbred, WI, populations (Charlesworth & lesworth (1987). A more recent review by Byers Charlesworth 1999): and Waller (1999) provides many more recent examples of inbreeding depression in plant popu- (2) lations and indicates that purging does not appear to act consistently as a major force in natural The coeffi cient B can be interpreted as the populations. In animals the situation is differ- reduction in log fi tness associated with com- ent but in the last decade there has been a rapid plete inbreeding (i.e. F = 1) and is widely used accumulation of evidence that indicates that as a measure of inbreeding depression. B is many wild animal populations exhibit inbreed- also a good measure of the number of lethal ing depression. For example, Soay sheep on the equivalents per gamete, which is defi ned as the island of Hirta (Saint Kilda archipelago, UK) number of deleterious alleles whose cumulative suffer signifi cant inbreeding depression in sur- effect equal that of one lethal (Cavalli-Sforza & vival (Coltman et al. 1999). More homozygous Bodmer 1971). sheep suffered higher rates of parasitism and, In small populations, the opportunities in turn, lower overwinter survival than did for mating are restricted, even under random heterozygous sheep. Another example comes mating patterns. Thus, mating among relatives from song sparrows living on Mandarte Island is common and the proportion of individuals (western Canada). In this case inbred birds died that are homozygous at many loci increases and at a much higher rate during a severe storm than results in inbreeding depression. The amount of did outbred birds (Keller et al. 1994). A more inbreeding depression manifested by a popu- recent study (Keller 1998) was able to quantify lation depends not only on F but also on the inbreeding depression in this population and opportunity for selection to purge recessive estimated that inbreeding depression in progeny lethal and sublethal mutations. Gradual inbreed- from a mating between fi rst-degree relatives was ing by incremental reductions in population 49%. The negative effect of inbreeding has also size over many generations allows selection been documented in the red-cockaded wood- to eliminate the lethal and sublethal mutations pecker living in southeastern USA. Inbreeding when they become homozygous (Falconer & reduced hatching rates, fl edgling survival and Mackay 1996). However, the component of recruitment to the breeding population (Daniels inbreeding depression due to more nearly addi- & Walters 2000). Extensive long-term data sets tive mutations of small effect are diffi cult to can help uncover inbreeding depression even purge by inbreeding (Lande 1995). Despite this in large populations with low inbreeding rates. theoretical expectation, recent reviews indicate An 18-year study of a large wild population of that purging is ineffi cient at reducing inbreed- collared fl ycatchers revealed that inbreeding was ing depression in small and inbred populations rare but when it did occur it caused a signifi cant (Allendorf & Ryman 2002, and references reduction in the egg-hatching rate, in fl edgling therein). skeletal size and in post-fl edging juvenile sur- Most of the evidence for inbreeding depres- vival (Kruuk et al. 2002). This study also found sion comes from domesticated or captive that the probability of mating between close rela- populations. This together with the theoretical tives (f = 0.25) increased throughout the breed- expectation that a large fraction of inbreeding ing season, possibly refl ecting increased costs of depression can be purged in small populations inbreeding avoidance. and the numerous mechanisms of inbreeding There is also evidence that stressful envi- avoidance observed in many species has led ronmental conditions can increase inbreeding many researchers to question the importance of depression. Crnokrak and Roff (1999) gathered inbreeding depression for the persistence of wild and analyzed a data set that included seven bird populations (Keller & Waller 2002). However, species, nine mammal species, four species of evidence of inbreeding depression in natural poikilotherms and 15 plant species and showed populations of plants has existed for quite some that conditions experienced in the wild increase 160 Gaggiotti • ANN. ZOOL. FENNICI Vol. 40 the cost of inbreeding. A more recent study Accumulation of slightly deleterious (Keller et al. 2002) shows that the magnitude mutations of inbreeding depression in juvenile and adult survival of cactus fi nches living in Isla Daphne Under more or less constant environments, Major (Galápagos Archipelago) was strongly mutations with phenotypic effects are usually modifi ed by two environmental conditions, food deleterious because populations tend to be well availability and number of competitors. In juve- adapted to the biotic and abiotic conditions of niles, inbreeding depression was present only in the environment they inhabit. Thus, a random years with low food availability, and in adults mutation is likely to disrupt such adaptation. inbreeding depression was fi ve times more In populations with moderate or large effective severe in years with low food availability and sizes, selection is very effi cient at eliminating large population size. detrimental mutations with large effects on fi t- Demonstrating the importance of inbreed- ness. However, mildly deleterious mutations ing depression in the wild does not necessar- with selection coeffi cient s ≤ 1/2Ne are diffi cult ily imply that it can cause wild populations to to remove because they behave as neutral muta- decline (Caro & Laurenson 1994). However, tions (Wright 1931). Thus, small population recent papers have demonstrated this connec- size hampers selection and increases the role of tion. Saccheri et al. (1998) studied the effect genetic drift in determining allele frequencies of inbreeding on in a large and fates. This increases the chance fi xation of metapopulation of the Glanville fritillary but- some of the deleterious alleles constantly sup- terfl y and found that extinction risk increased plied by mutation and result in the reduction signifi cantly with decreasing heterozygosity, of population mean fi tness, which eventually even after accounting for the effects of ecologi- leads to population extinction (Muller 1964). cal factors. Larval survival, adult longevity and Initially this process was assumed to represent egg-hatching rate all were adversely affected by a threat only to asexual populations because in inbreeding and seem to be the fi tness component the absence of recombination, offspring carry responsible for the relationship between inbreed- all the mutations present in their parent as well ing and extinction. More indirect evidence is as any newly arisen mutation (Muller 1964). provided by Newman and Pilson (1997). They Mathematical models of this process (Lynch & established experimental populations of the Gabriel 1990, Lynch et al. 1993) show that as annual plant Clarkia pulchella that differed in mutations accumulate, there is a gradual reduc- the relatedness of the founders. All populations tion in population size. This increases the effect were founded by the same number of indi- of random genetic drift, which enhances the viduals, but persistence time was much lower in chance fi xation of future deleterious mutations, those whose founders were related. Additional leading to further fi tness decline and reduction evidence comes from the study of an isolated in population size. Due to this positive-feedback population of adders in Sweden (Madsen et al. mechanism (see Fig. 2), the fi nal phase of popu- 1999) that declined dramatically around 35 years lation decline (when growth rate is negative) ago and was on the brink of extinction due to occurs at an accelerating rate, a process known severe inbreeding depression. The introduction as “mutational meltdown”. of twenty adult male adders from a large and Although recombination can slow down the genetically variable population led to a rapid mutational meltdown to some extent, sexual population recovery due to a dramatic increase populations are also at risk of extinction due to in recruitment. mutation accumulation (Lande 1994, Lynch et al. All the evidence discussed above indicate 1995). Lande (1994) studied this problem using that inbreeding depression is common in wild a model of a randomly mating population with populations and can represent a short-term no demographic or environmental stochasticity. extinction threat specially if populations are He considered only unconditionally deleterious subjected to environmental stress or to sharp mutations of additive effects and derived ana- population declines. lytical approximations for the mean time until ANN. ZOOL. FENNICI Vol. 40 • Genetic threats to population persistence 161 extinction for two cases: (a) all mutations had the same selection coeffi cient s, and (b) there is variance in s. Lynch et al. (1995) provided a more detailed analysis of scenario (a) and check the analytical results using computer simulations. With constant s, the mean time to extinction, , is an approximately exponential function of effective population size. Since the mean time to extinction increases very rapidly with increasing

Ne, the fi xation of new mutations poses little risk of extinction for populations with a Ne of about Fig. 2. Schematic showing the positive feedback loop 100 (Lande 1994). However, with variance in s, that leads to a mutational meltdown. the mean time to extinction increases as a power of population size. If s is exponentially distrib- 2 uted, then is asymptotically proportional to Ne . solved. The fi rst one is that there is a controversy Since in this case the increase in with popula- about the estimates of per-genome mutation tion size is more gradual than for constant s, the rates, U, and the average fi tness cost per muta- risk of extinction is much greater. For reasonable tion, s, used in the meltdown models. These were variance in s (coeffi cient of variation of about 1) based on mutation accumulation experiments the mutational meltdown poses a considerable using Drosophila melanogaster that resulted in risk of extinction for populations with Ne as large U = 1 and a reduction in fi tness of about 1%–2% as a few thousand individuals (Lande 1994). If, (Lande 1994, Lynch et al. 1995). Recent stud- as generally agreed, the ratio of effective size ies (Garcia-Dorado et al. 1999; see also Zeyl & to total population size is around 0.1–0.5, then DeVisser 2001) that included D. melanogaster as moderately sized populations (several thousand well as Caenorhabditis elegans and Saccharo- individuals) may face extinction due to genetic myces cerevisiae, resulted in U orders of magni- stochasticity. tude less than one. Additionally, some mutation There is a paucity of empirical evidence for accumulation experiments (Keightley & Cabal- the mutational meltdown. Experimental evidence lero 1997, Caballero et al. 2002) reported aver- for the accumulation of deleterious mutations age fi tness effects one order of magnitude higher due to genetic drift exist but does not directly than those reported previously. The assumption address the risk of extinction (Zeyl et al. 2001). of additive effects is also questioned by Garcia- As of today, only Zeyl et al. (2001) explicitly Dorado et al. (1999), who reported estimates of explored the plausibility of the mutational 0.1 for the average coeffi cient of dominance. The meltdown using an experimental approach. new estimates of U and s would lead to much They established 12 replicate populations of lower rates of population decline making the Saccharomyces cerevisiae from two isogenic mutational meltdown less likely. Caballero et al. strains which genomewide mutation rates dif- (2002) used a combination of mutation accumu- fered by approximately two orders of magnitude. lation experiments and computer simulations and They used a transfer protocol that resulted in an concluded that a model based on few mutations effective population size near 250 and after more of large effect was generally consistent with their than 100 daily bottlenecks, the yeast population empirical observations. with elevated mutation rates showed a tendency Finally, an additional criticism concerns the to decline in size, while the populations with fact that mutational meltdown models ignore wild-type mutation rates remained constant. the effect of benefi cial and back mutations. The Moreover, there were two extinctions among the inclusion of these types of mutations indicates mutator populations. These results provide sup- that only very small populations would face port for mutational meltdown models. the risk of extinction due to genetic stochastic- Despite this preliminary empirical support ity (Poon & Otto 2000, Whitlock 2000). Recent there are a number of issues that remain unre- estimates of mutational effects using mutation 162 Gaggiotti • ANN. ZOOL. FENNICI Vol. 40 accumulation experiments with Arabidopsis this can limit the purging of inbreeding depres- thaliana indicate that roughly half of the muta- sion. However, this negative effect is unlikely tions reduce reproductive fi tness (Shaw et al. to offset the positive effects of increased mean 2002). Additionally, the per-generation, genom- population fi tness due to heterosis and the arrival ewide mutation rate is around 0.1–0.2. These of immigrants with high fi tness (outbred vigour). new results suggest that the risk of extinction Heterosis refers to the increased fi tness observed for small populations may be lower than initially among offspring from crosses among popula- thought. This issue is reviewed in more detail by tions. Different populations tend to fi x different Whitlock et al. (2003). random subsets of deleterious alleles that mask At the moment it is not possible to provide a each other when populations are crossed (Crow clear evaluation of the importance of the muta- 1948, Whitlock et al. 2000). Thus, compared tional meltdown process. This will only be to resident genomes, initially rare immigrant possible once the existing controversy over the genomes are at a fi tness advantage because their properties of spontaneous mutations is resolved descendants are more likely to be heterozygous (Poon & Otto 2000). This in turn requires knowl- for deleterious recessive mutations that cause edge of the form of the distribution of mutational inbreeding depression in the homozygous state effects and the extent to which is modifi ed by (Ingvarsson & Whitlock 2000, Whitlock et al. environmental and genetic background as well 2000). Several recent studies have provided as the contribution of basic biological features fairly conclusive evidence supporting this expec- such as generation length and genome size to tation. Saccheri and Brakefi eld (2002) carried out interspecifi c differences in the genomic mutation an experimental study with the butterfl y Bicyclus rate (Lynch et al. 1999). anynana. They focused on the consequences of a single immigration event between pairs of equally inbred local populations. The experiment Local extinction in the presence consisted in transferring a single virgin female of migration from an inbred (donor) population to another equally inbred (recipient) population. The spread Up to this point I have focused on the ecologi- of the immigrantʼs and all the residentsʼ genomes cal and genetic factors that underlie the extinc- was monitored during four consecutive gen- tion of isolated populations. Although habitat erations by keeping track of the pedigree of all fragmentation is leading to population isolation, individuals in the treatment populations. They under natural conditions few populations can be replicated this experimental design and observed considered completely isolated. In most cases, a rapid increase in the contribution of the ini- they are connected to other populations through tially rare immigrant genomes to the local popu- migration, a process that has important implica- lations gene pool. Additional strong support is tions for population persistence. provided by Ebert et al. (2002) who carried out Migration can have both positive and nega- experiments using a natural Daphnia metapopu- tive effects on the demography and genetics of lation in which genetic bottlenecks and local local populations. The negative effects on the inbreeding are common. Their results indicate demography are related to the spread of disease that heterosis amplifi es gene fl ow several times and predators to populations where they were not more than would be predicted from the nominal present. The benefi cial effect of migration arises migration rate. Less conclusive evidence comes because immigrants from surrounding popula- from experiments with the dioecious plant Silene tions might prevent the extinction of small popu- alba (Richards 2000). Isolated populations of this lations, a process known as the ‘rescue effectʼ plant suffer substantial inbreeding depression, (Gotelli 1991). presumably due to the absence of gene fl ow, and Migration also has both benefi cial and the resulting high degree of relatedness among detrimental genetic effects. Many populations individuals. Richards (2000) measured gene fl ow experience gene fl ow at high enough rates to among experimental populations separated by reintroduce quickly via immigrants; 20 m and used paternity analysis to assign all ANN. ZOOL. FENNICI Vol. 40 • Genetic threats to population persistence 163 Mean

0F1 F2 F3 Generation Fig. 3. Potential effects of migration on population fi tness: heterosis increases fi tness (solid line and diamonds), heterosis followed by outbreeding depression leads to a short lived fi tness increase followed by a decline (dotted line and squares), outbreeding depression leads to steady decline in fi tness (dashed line and triangles). seeds to either local males or to gene fl ow from and recombination only begin to break apart other nearby experimental population. When coadapted genes from a single line in the F2 recipient populations were inbred, unrelated generation (Dobzhansky 1950, 1970). Thus, males from the experimental population 20 m outbreeding depression is demonstrated when away sired more offspring than expected under the performance of F2s is less than the aver- random mating. This can be due to some form age of immigrants and natives (Lynch & Walsh of pollen discrimination that may be infl uenced 1998: p. 225). However, few studies of natural by early acting inbreeding depression (Richards populations track the contribution of immigrants

2000) or to heterosis per se. More evidence beyond the F1 generation (Marr et al. 2002). The comes from experiments with Drosophila mela- few studies that go beyond the F1 generation nogaster that measured the genetic contribution indicate that outbreeding depression may be of single immigrants into inbred populations by common in the wild. Marr et al. (2002) showed measuring the relative frequency of immigrant that the same population of song sparrows in the marker alleles in the fi rst and second generation Mandarte Islands (see above) that manifested (Ball et al. 2000). When immigrants were out- heterosis among immigrant offspring, also show bred, the mean frequency of the immigrant allele signs of outbreeding depression in the F2 genera- in the fi rst and second generation after migration tion. Studies of the tidepool copepod Tigriopus was signifi cantly higher than its initial frequency. californicus show that crosses between popula-

They attributed this result to the initial outbred tions typically result in F1 hybrid vigour and F2 vigour of immigrant males but the possibility hybrid breakdown for a number of measures con- that heterosis could have played a role was not nected with fi tness (Burton 1987, Burton 1990a, completely excluded. 1990b, Edmands & Burton 1998, Burton et al. Outcrossing does not always enhance fi tness 1999). Recent work (Edmands 1999) has shown (Fig. 3). The introduction of immigrant genomes that the detrimental effects of breaking up coad- from a highly divergent population can reduce aptation are magnifi ed by increasing genetic dis- mean population fi tness if hybridization disrupts tance between populations. This same effect was coadapted gene complexes or favourable epi- shown for the shrub Lotus scoparius but in this static interactions, this phenomenon is known as case outbreeding depression was already pres- outbreeding depression. Outbreeding depression ent in the F1 generation (Montalvo & Ellstrand may not be expressed until the F2 generation or 2001). Other plant species that show outbreeding later because F1s carry a haploid set of chromo- depression are Ipomopsis aggregata (Waser et al. somes from each parental line, and segregation 2000) and Silene diclinis (Waldmann 1999). 164 Gaggiotti • ANN. ZOOL. FENNICI Vol. 40

Finally, the arrival of migrants from large value effective size (the number of individuals in populations can increase genetic variability, and, an ideal population that would lose heterozygos- therefore, improve the evolutionary potential ity at the same rate as the actual population) of a of the species as a whole. The extent to which metapopulation and concluded that the decrease migration can replenish genetic variability in the effective size of the metapopulation is due depends on the population dynamics and the to a sharp increase in the variance in reproduc- pattern of migration into local populations. tive success among individuals brought about by Populations with positive growth rates can population turnover. Individuals that recolonise rapidly recover lost genetic variability but sink a habitat patch have an expected reproductive populations will only be able to maintain genetic output of N/k > 1, where N is the local popula- variability under migration patterns with low tion size and k is the propagule size. On the propagule size variance (Gaggiotti 1996, Gag- other hand individuals in the demes that are giotti & Smouse 1996). However, this long-term about to go extinct fail to contribute progeny to benefi cial effect of migration may be offset by the metapopulation. All the studies mentioned the introduction of maladapted genes, which above considered a metapopulation composed of could lead to a migrational meltdown (Ronce & qualitatively similar demes (i.e. equal carrying Kirkpatrick 2001). Increased dispersal may lead capacities). If habitat patches differ in quality, to the loss of local adaptation in some popula- which is typically the case for source-sink meta- tions, the appearance of source-sink dynamics, populations, population turnover does not have and the evolution of narrow niches (Kirkpatrick a very large effect because genetic diversity is & Barton 1997, Ronce & Kirkpatrick 2001). This stored in the extinction resistant source popula- process, called migrational meltdown because tions. Moreover, sink populations can maintain a small populations experience a downward spiral large fraction of the genetic variability present in of maladaptation and shrinking size, is discussed the source population under migration patterns in the next section. with a low variance in propagule size (Gaggiotti 1996). The theoretical study of inbreeding depres- Extinction in a metapopulation sion in a metapopulation has received little atten- context tion but recently, Whitlock (2002) addressed this problem in some detail. When local populations The same factors responsible for the genetic contribute to the next generation in proportion threats to the survival of isolated populations are to their average fi tness (i.e. under hard selec- operating at the metapopulation level but they tion), a metapopulation will respond more effi - have not been as well studied in this context. ciently to selection than a panmictic population The best studied factor is the loss of genetic of equal size. This occurs because with local variability due to population turnover. Slatkin mating, recessive alleles are more likely to be (1977) was the fi rst to show that the extinction expressed as homozygotes, thus the response to and recolonisation of local populations causes selection on recessive alleles is proportional to a major reduction in the genetic diversity main- their homozygous effect rather than the weaker tained within demes and in the total metapopula- heterozygous effect. Under these circumstances, tion. The reduction in the total amount of genetic the purging of deleterious mutations is more diversity is more pronounced when colonizing pronounced and is not temporary because of propagules are formed by individuals from persistent migration, which brings new variation the same deme (“propagule pool” model) than into each local population. Thus, the equilibrium when they are formed by individuals coming frequency of deleterious alleles is lower than in from all extant demes (“migrant pool” model). an undivided population of equal total size and Maruyama and Kimura (1980) demonstrated this results in reduced inbreeding depression. same effect using a formulation that focused on Higgins and Lynch (2001) extended the the mutation effective size. Whitlock and Barton mutational meltdown theory described above (1997) used a formulation based on the eigen- to cover the case of metapopulations using an ANN. ZOOL. FENNICI Vol. 40 • Genetic threats to population persistence 165 individual-based model that includes stochas- tive effect of migration but they considered a tic, demographic, environmental, and genetic model with two discrete habitat types connected mechanisms. The metapopulation structure is by migration. In this case, increasing migration modelled as a linear array of patches connected rate above some threshold value results in the by either nearest-neighbour (stepping-stone), collapse of the total population size and the global (island), or intermediate dispersal. The complete loss of one of the two habitats. As mutational effect is modelled in such a way that opposed to Kirpatrick and Barton analysis, there mutations of large effect are almost recessive, is no metapopulation extinction. Ronce and whereas those of small effect are almost additive. Kirpatrick (2001) attributed this disagreement The results show that for metapopulations with between the two models to the assumption of more than a few patches, mutational accumula- infi nite space made by Kirpatrick and Bartonʼs tion is expected to accelerate extinction time by model: the distance traveled by migrants and many orders of magnitude, compared to a glob- thus the maladaptation of such migrants to local ally dispersing metapopulation without mutation conditions increase indefi nitely with the migra- accumulation. Moreover, extinction because of tion rate. This indicates that the migrational mutation accumulation can be quite rapid, on meltdown is unlikely to cause metapopulation the order of tens of generations. In general, the extinction but it can lead to the extinction of results indicate that the mutational meltdown local populations. may be a signifi cant threat to large metapopula- tions and would exacerbate the effects of habitat loss or fragmentation on metapopulation viabil- Discussion ity. These conclusions, however, where reached under the assumptions of an expected per-gen- Much progress has been made towards gain- eration genome wide mutation rates of 1 and ing a better understanding of the interaction unconditionally deleterious mutational effects. between demographic and genetic factors in As mentioned before, these two assumptions the extinction of populations. For example, it is have been put under close scrutiny and prelimi- now clear that their interaction can lead to posi- nary evidence indicates that they may not be of tive feedback loops involving ever decreasing general applicability. population sizes and eventual extinction (e.g. An additional mechanism for extinction in mutational meltdown). A substantial amount of a metapopulation context is motivated by the empirical evidence has been gathered supporting idea that peripheral populations receive gene the importance of genetic threats. This is particu- fl ow from the center of the speciesʼ range. These larly the case for inbreeding depression, which is immigrant genes will typically be adapted to the the most immediate genetic threat to the survival conditions at the range center and could inhibit of small populations. Theoretical work indicates adaptation at the periphery (Mayr 1963). Kir- that the accumulation of mildly deleterious patrick and Barton (1997) used a quantitative mutations could be potentially important in the genetic model to study the evolution of a species short term while the loss of genetic variability is range in a linear habitat with local migration. important in the long term. The model tracks evolutionary and demographic Despite this progress, there are still some few changes across space and time and assumes that unresolved issues that need to be clarifi ed before variation in the environment generates patterns being able to fully evaluate the importance of of selection that change in space but are constant genetic threats. In particular, the current con- in time. Among other things, the results show troversy (Garcia-Dorado et al. 1999, Lynch et that a speciesʼ range can contract as the dispersal al. 1999, Caballero et al. 2002) surrounding the rate increases and extinction can result if condi- genome-wide mutation rates and their average tions change too rapidly as one moves across effect makes it diffi cult to have a clear sense of the habitat, even if the species remains perfectly the importance of the mutational meltdown for adapted to the habitat at the range center. Ronce the extinction of local populations and whole and Kirpatrick (2001) also studied the maladap- metapopulations. More research on the mutation 166 Gaggiotti • ANN. ZOOL. FENNICI Vol. 40 process underlying the mutational meltdown and Acknowledgements more empirical demonstration of the feasibility of this phenomenon are needed. Additionally, This work was supported by the Academy of Finland through models such as that of Higgins and Lynch (2001) its Finnish Centre of Excellence Programme (2000–2005). The original manuscript benefi ted from the comments of a should be extended to include benefi cial muta- reviewer and the editor. tions. Additional work has to be carried out in order to evaluate the importance of the genetic References rescue effect due to heterosis and, in particular, to understand how outbreeding infl uences the Allendorf, F. W. & Ryman, N. 2002: The role of genetics in mean fi tness of natural populations. This will population viability analysis. — In: Beissinger, S. R. & require carrying out experiments that follow McCullough, D. R. (eds.), Population viability analysis: the fate of descendants from immigrants beyond 50–85. University of Chicago Press, Chicago. the F generation. It is possible that the results Ball, S. J., Adams, M., Possingham, H. 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