PerspectiveGenetic rescue: A critique of the evidence supports maximizing genetic diversity rather than minimizing the introduction of putatively harmful genetic variation
Introduction
The inevitable loss of genetic variation from small isolated populations increases their risk of extinction due to inbreeding depression and reduced ability to adapt to environmental change. Many of these population fragments can potentially be saved from extinction by genetic rescue: augmentation of genetic diversity that reduces inbreeding depression, increases population size and ability to evolve (Frankham, 2015, Frankham, 2016; Whiteley et al., 2015). Genetic rescue enhances fitness and population growth, as long as non-genetic drivers of decline are also managed effectively (Tallmon et al., 2004; Bell et al., 2019; Ørsted et al., 2019; Hemphill et al., 2020).
There is ample evidence (Frankham et al., 2017) that loss of genetic variation increases extinction risk as part of the ‘small population paradigm’ (Caughley, 1994). However, a few inbred wildlife populations, including island foxes (Urocyon littoralis), are reputed to have persisted for long periods in isolation (Coonan et al., 2010; Reed, 2010; Hofman et al., 2016). Some authors claim that this challenges the small population paradigm and question the importance of genetic variation for population persistence and the need for genetic rescue in some situations (Robinson et al., 2016, Robinson et al., 2018).
This purported challenge to the richly supported small population paradigm could have a major, unwarranted influence on the application of genetic management of small and isolated populations of threatened species, either hindering it: ‘the island fox illustrates a scenario in which genetic restoration through human-assisted gene flow could be a counterproductive or even harmful conservation strategy.’ (Robinson et al., 2018) or changing its implementation: ‘the idea that founders from historically isolated populations should be selected to mitigate the risk of future inbreeding depression stands in contrast with the conventional wisdom of selecting individuals with the most diversity from nearby populations. However, this alternative should be considered as a potentially more successful strategy for preserving species consisting of small and isolated populations’ (Robinson et al., 2019), and ‘Our findings challenge the traditional conservation paradigm that focuses on genetic diversity in assessing extinction risk in favor of a new view that emphasizes minimizing deleterious variation.’ (Kyriazis et al., 2019 non-peer-reviewed pre-print). At the time of writing, that non-peer-reviewed pre-print had been cited as evidence regarding the best approaches to genetic management at least 8 times in peer-reviewed articles (Supplementary material) and highlighted in the science media (Pennisi, 2019). The influences of these papers on wildlife management are already evident: for example, de Manuel et al. (2020) concluded in relation to very low genetic diversity in the Gir lion population ‘one future action to consider would be boosting their genetic diversity through outbreeding with such lions. However, in this regard, we are fully aware that this strategy would be both politically challenging, and, in light of recent observations on the effect of genetic introductions in the Isle Royale wolves (37), not guaranteed to be beneficial, so such decisions should not be taken lightly.’ (reference 37 is Robinson et al., 2019).
It is important that genetic management be applied effectively when required, because most species have fragmented distributions resulting from human activities, many with small isolated populations suffering low genetic diversity, inbreeding and consequent reduced fitness and an elevated risk of extinction (Frankham et al., 2017). Established guidelines for genetic rescue recommend using source populations that have a low risk of causing outbreeding depression, are genetically diverse and have the lowest mean kinship (co-ancestry) with the population needing rescue, because this minimizes inbreeding in the rescued population, maximizes enhancement of genetic diversity, which facilitates adaptation to changing environments, and is empirically extremely successful (Frankham, 2015; Whiteley et al., 2015; Frankham et al., 2017). The suggested opposing strategy of introducing individuals from smaller, more-inbred populations is cast as minimizing the introduction of harmful variation at the expense of lower genetic diversity and higher inbreeding in the recipient population. This proposal is based on the idea that in smaller, partially inbred populations highly harmful mutations would have been removed by ‘purging’ (selection against harmful variants, particularly recessive and partially-recessive alleles) (Robinson et al., 2018, Robinson et al., 2019; Kyriazis et al., 2019 pre-print).
Our objectives in this perspective are to assess claims that:
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‘The long-term persistence of island foxes despite their small population sizes and increased genetic load presents a challenge to the small-population conservation paradigm’ (Robinson et al., 2016).
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island foxes show no inbreeding depression and the long-term persistence of island fox populations ‘provides a model for preservation of small fragmented populations’ (Robinson et al., 2018).
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the history of the Isle Royal wolf population is a good model for the probable results of genetic rescue using outbred immigrants from a large population (Robinson et al., 2019; Kyriazis et al., 2019 pre-print).
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immigrants from small ‘historically isolated populations’ (Robinson et al., 2019) or ‘small or moderate size populations’ (Kyriazis et al., 2019 pre-print) will have more beneficial genetic rescue impacts when introduced into small, isolated inbred populations than will immigrants from larger, more outbred populations, due to the prior purging of highly harmful alleles from smaller populations.
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computer simulations support the use of small, presumably purged, populations as sources for genetic rescue (Robinson et al., 2019; Kyriazis et al., 2019 pre-print).
These five claims would have far-reaching implications for biological conservation if valid, and are assessed below in 2 Persistence of a few inbred populations does not invalidate the small population paradigm, 3 Island foxes probably suffer from inbreeding depression and are not an appropriate model for the management of historically fragmented populations, 4 The history of the Isle Royal wolf population is not an appropriate model for a genetic rescue, 5 Theory and a large body of empirical data support the preferential use of large source populations for genetic rescue rather than smaller ones, 6 Problems and limitations of the simulation modeling, respectively.
Section snippets
Persistence of a few inbred populations does not invalidate the small population paradigm
Proposed cases of long-term survival of populations with low genetic variation may have overlooked past gene flow, as for the Isle Royale wolf population (Hedrick et al., 2014). Although Robinson et al. (2018) did not detect gene flow among Californian Channel Island fox populations with their sample size of a single fox per island (except two from one island), studies using ~20–40 individuals per population found clear evidence of gene flow, inconsistent with long-term isolation (Hofman et
Island foxes probably suffer from inbreeding depression and are not an appropriate model for the management of historically fragmented populations
Absence of evidence is not evidence of absence. Claims such as those of Robinson et al. (2018) that populations show no inbreeding depression would be more credible if they demonstrated appropriate design and power to register any inbreeding depression present. Detecting inbreeding depression requires comparisons of inbred and non-inbred individuals in similar environments, with sufficient estimation of inbreeding levels, variance in inbreeding, and sample sizes (Charlesworth and Willis, 2009;
The history of the Isle Royal wolf population is not an appropriate model for a genetic rescue
Wolves, probably one female and two males, colonized Isle Royale in Lake Superior, Michigan, USA from the mainland in 1949 or 1950 (Adams et al., 2011), when the channel between mainland and island froze. The 544 km2 island can support only ~24 wolves with an effective population size of ~3.8 (Adams et al., 2011). By the late 1990s, the island population was extremely inbred. Mainland male M93 migrated to the island in 1997. His reproductive fitness was so much higher than that of his inbred
Benefits of using immigrants from large source populations
Introducing individuals from large, non-inbred source populations is, on average, about twice as effective at improving fitness and genetic diversity as introducing them from small inbred populations (Frankham, 2015) and it will be longer before additional gene flow is required when more diverse sources are used (Frankham et al., 2017).
Overturning the large body of evidence supporting current genetic rescue guidelines based on increasing genetic diversity and reducing inbreeding would require
Description of the Robinson/Kyriazis modeling approach
Robinson et al., 2018, Robinson et al., 2019 and Kyriazis et al. (2019 pre-print) simulated isolated island population scenarios using versions of the SLiM software package (Haller and Messer, 2019), using similar genetic models. SLiM allows for inclusion of an extensive range of demographic and genetic variables for modeling finite populations, offering valuable potential for projecting population futures and making conservation recommendations using available evidence. The modeling by
Conclusions and recommendations
The current recommendation for genetic rescue, to choose a source population that will maximize genetic diversity in the target population, is well-supported by a large body of theory and empirical evidence, including planned experiments and successful genetic rescues. Guidelines for planning genetic rescues are provided in Frankham et al. (2017) and include decision-support tools for screening potential source populations for the risk of outbreeding depression if crossed with target
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
We thank Anthony Starfield for providing useful papers on best modeling practices and four anonymous reviewers for their detailed and helpful comments. PS thanks his research group for helpful comments, particularly Diana Robledo-Ruiz. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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