Molecular Ecology (2015) 24, 2595–2597
NEWS AND VIEWS
PERSPECTIVE
Genetic rescue: a safe or risky bet? DONALD M. WALLER Department of Botany, University of Wisconsin - Madison, 430 Lincoln Drive, Madison, WI 53706-1381, USA
Small and isolated populations face threats from genetic drift and inbreeding. To rescue populations from these threats, conservation biologists can augment gene flow into small populations to increase variation and reduce inbreeding depression. Spectacular success stories include greater prairie chickens in Illinois (Westermeier et al. 1998), adders in Sweden (Madsen et al. 1999) and panthers in Florida (Johnson et al. 2010). However, we also know that performing such crosses risks introducing genes that may be poorly adapted to local conditions or genetic backgrounds. A classic example of such ‘outbreeding depression’ occurred when different subspecies of ibex from Turkey and the Sinai were introduced to assist recovery of an ibex population in Czechoslovakia (Templeton 1986). Despite being fertile, the hybrids birthed calves too early, causing the whole population to disappear. In the face of uncertainty, conservation biologists have tended to respect genetic identity, shying away from routinely crossing populations. In this issue of Molecular Ecology, Frankham (2015) compiles empirical data from experimental studies to assess the costs and benefits of between-population crosses (Fig. 1). Crosses screened to exclude those involving highly divergent populations or distinct habitats show large heterosis with few apparent risks of outbreeding depression. This leads Frankham to advocate for using assisted gene flow more widely. But do the studies analysed in this meta-analysis adequately test for latent outcrossing depression? Keywords: adaptation, conservation genetics, ecological genetics, inbreeding, outbreeding depression, population genetics – empirical Received 26 March 2015; revision accepted 24 April 2015 Habitats around the world are shrinking and becoming more isolated causing populations to slip below the threshold of viability and adaptive potential. In response, island biogeography predicts declines in both species diversity and allelic variation within the surviving populations (Jaenike 1973). Without gene flow to sustain genetic variation, genetic drift causes populations to lose variation and fix Correspondence: Donald M. Waller, Fax: (608) 262 7509; E-mail:
[email protected]
© 2015 John Wiley & Sons Ltd
more mutations as the genetically effective population size, Ne, declines. This robs populations of genetic variation just as their need to respond to environmental changes is increasing. Mutations with mildly deleterious effects (s much below 1/Ne) that are efficiently culled in larger populations instead become invisible to selection. They thus accumulate, creating ‘drift load’ (Whitlock et al. 2000). Inbreeding presents the most immediate threat to small populations by cumulatively increasing the frequency of homozygotes, exposing deleterious recessive alleles. Although such alleles are individually rare, collectively their effects are profound, greatly reducing fitness via inbreeding depression, even in wild populations (Crnokrak & Roff 1999; Keller & Waller 2002). Selection quickly purges highly deleterious recessive alleles, but this accelerates the fixation of mildly deleterious alleles, increasing drift load. Introducing new genotypes into such populations brings great and immediate increases in fitness as new alleles mask these deleterious recessives. The resulting heterosis increases both individual and population fitness. Given these genetic threats and the proved efficacy of population crosses for boosting fitness, why not apply such rescue efforts routinely to all populations suspected of suffering from drift or inbreeding? The issue here concerns the risks of ‘outbreeding depression’ (OD). Several distinct mechanisms can act to reduce fitness in between-population crosses. Most simply, if populations are strongly adapted to local conditions, introduced genotypes may lack appropriate genetic variation to fit local circumstances. Locally adapted populations can then lose fitness by gaining genes or behaviours poorly suited to local conditions. Such effects diminish or reverse gains in fitness due to heterosis. Populations diverge over time in response to both selection and drift. This divergence also causes populations to accumulate fixed differences including genes co-evolved to function well in these specific and distinct genetic backgrounds. Such genes may, however, not ‘play well’ with other genetic backgrounds. These ‘Dobzhansky–M€ uller’ genetic incompatibilities arise both among nuclear genes and between nuclear and cytoplasmic genes. They eventually become strong enough to spur full reproductive isolation and speciation. Such epistatic incompatibilities are usually absent in the F1, while ancestral chromosomes remain intact, but emerge in the F2 and later generations as recombination breaks up favourable gene complexes. We thus need multigeneration studies to evaluate their existence, severity and longevity (Tallmon et al. 2004). The diversity of genetic mechanisms and possible outcomes here means theory cannot make accurate predictions regarding the magnitude of OD. So what levels of outbreeding depression occur in nature? In a study of largemouth bass (Micropterus salmoides), Goldberg et al. (2005) initially found a decrement of 14% in
2596 N E W S A N D V I E W S : P E R S P E C T I V E Fig. 1 Some of the species used in the meta-analysis of Frankham (2015). Clockwise from top left: White Campion (Silene alba), Common Adder (Vipera berus), Wood Avens (Geum urbanum) and Housefly (Musca domestica). All photos are in the public domain.
progeny of a cross between two populations grown in a benign hatchery environment. When fry were exposed to a viral pathogen, however, F2 hybrids suffered 3.69 higher mortality than either F1 generation hybrids or wild-type parental fish, possibly reflecting disrupted coadapted gene complexes in their immune systems. Conversely, initial estimates of 30% for outbreeding depression in F1 seedlings of the montane plant, Ipomopsis aggregata, declined to 5-10% as these plants matured and experienced different environmental conditions (Waser et al. 2000). Edmands (2007) summarized OD in crosses involving some 35 species. While some of these were dramatic, many involved distant crosses between populations or species where we expect genetic incompatibilities. Whitlock et al. (2013) reviewed 98 studies, again including wider crosses and not favouring studies with evidence of local inbreeding. They found fitness traits to be unaffected in the F1 while suffering a modest decline in the F2. Faced with uncertainty regarding both potential costs and the fitness benefits likely in crossed populations, conservation biologists have been shy to pursue genetic rescue. Perhaps too shy given that such concerns could inhibit efforts to rescue populations even in situations where it could work well. Frankham (2015) found few examples of efforts at genetic rescue among threatened wild populations. To minimize the risks of OD, Frankham et al. (2011) extended relevant theory to predict the likelihood of OD in populations subject to selection and drift for various periods of time. They also provided a few simple rules to
avoid the risks of OD such as avoiding distant crosses, crosses between divergent karyotypes and those growing under different environmental conditions. Their list deserves wide attention and implementation. Frankham (2015) here reviews 156 studies from the experimental genetics literature to cull data on just how fitness is affected in crosses between isolated and presumed inbred populations. Although many are laboratory studies based on model organisms such as Drosophila, the genetic principles being tested are universal. In addition, he applied Frankham et al.’s (2011) selection criteria to avoid studies based on wide crosses. Using both parametric and nonparametric methods, he finds overwhelming evidence for heterotic effects boosting the fitness of F1 hybrids between isolated populations. Furthermore, the extent of this heterosis increases in cases where crosses reduce maternal inbreeding more, as we expect it should. Benefits also tend to increase in stressful environments (148%, vs. 45% in benign environments), as noted by others (Hedrick 1994; Fox & Reed 2011). These results confirm the beneficial effects of outcrossing and thus the strong potential for genetic rescue. So what are the risks from outcrossing depression? Recall that to assess these, we must examine not only fitness increases in the F1 where heterosis from nuclear genes is maximum but also potential declines in fitness thereafter when epistatic incompatibilities become manifest, ideally in the F3 when maternal and zygotic inbreeding levels have stabilized (Fenster & Galloway 2000). Frankham (2015) reports ratios of F1 and F2 © 2015 John Wiley & Sons Ltd
N E W S A N D V I E W S : P E R S P E C T I V E 2597 and later generation progeny fitnesses to their corresponding (inbred) parent fitness. Surprisingly, he finds that F2+ progeny have significantly higher relative fitness than F1 progeny (see Frankham’s Table 1). He concludes that outbreeding depression is minor in these crosses and small relative to inbreeding maternal effects. He points out that any maternal effects acting to depress F1 fitness would dissipate in later generations, allowing fitness to rebound, accounting for these surprising results.. While it is tempting to accept these explanations, concern arises in that these means are computed from different sets of studies. Only 37 of the 156 studies analysed provide any data on F2+ fitness. To gain rigour, we might instead apply paired t-tests that contrast only values pertaining to the same population, species and study while controlling for maternal inbreeding effects. With too few studies including data on both F1 and F2+ fitnesses, however, statistically meaningful comparisons were precluded (R. Frankham, pers. comm.) The difference Frankham reports between F1 and F2+ mean fitnesses could thus reflect differences between these two groups in their levels of inbreeding (F = 0.62 and 0.44, respectively), the species studied and/or the circumstances they grew under. Focusing on differences in inbreeding, the higher parental F values found in studies with F1-only data must reflect populations that have experienced more inbreeding. In these, we expect more purging of deleterious recessive mutations to occur, ameliorating inbreeding depression and thus the ratio of F1 to parental fitness. This might account for some of the difference Frankham reports – without having to invoke maternal effects. In any event, Frankham’s assertion that 93% of the cases screened show low risk for OD overstates the case – at least for OD that reflects nuclear genetic incompatibilities. Additional welldesigned studies with ample sample sizes extending to the F3 generation are needed to resolve just how common and important OD is even when extreme crosses are avoided. Frankham’s work convincingly demonstrates how we can often overcome the sinister effects of inbreeding in small isolated populations by crossing populations. A few dramatic, but perhaps easily avoided, cases of outbreeding depression have perhaps dissuaded many conservation biologists from making more efforts to genetically rescue isolated populations. Despite remaining uncertainty regarding how often outbreeding depression occurs and its magnitude, Frankham et al.’s (2011) rules probably minimize these risks. If we are to halt the slide of threatened species towards extinction, we must learn how to sustain the viability of their populations by interconnecting habitats more effectively and, where this is not feasible, by designing gene flow programs to make genetic rescue a safe, common and accepted practice.
© 2015 John Wiley & Sons Ltd
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The author is solely responsible for this work. doi: 10.1111/mec.13220
