Reviewing the consequences of genetic purging on the success of rescue programs

Abstract

Genetic rescue is increasingly considered a promising and underused conservation strategy to reduce inbreeding depression and restore genetic diversity in endangered populations, but the empirical evidence supporting its application is limited to a few generations. Here we discuss on the light of theory the role of inbreeding depression arising from partially recessive deleterious mutations and of genetic purging as main determinants of the medium to long-term success of rescue programs. This role depends on two main predictions: (1) The inbreeding load hidden in populations with a long stable demography increases with the effective population size; and (2) After a population shrinks, purging tends to remove its (partially) recessive deleterious alleles, a process that is slower but more efficient for large populations than for small ones. We also carry out computer simulations to investigate the impact of genetic purging on the medium to long term success of genetic rescue programs. For some scenarios, it is found that hybrid vigor followed by purging will lead to sustained successful rescue. However, there may be specific situations where the recipient population is so small that it cannot purge the inbreeding load introduced by migrants, which would lead to increased fitness inbreeding depression and extinction risk in the medium to long term. In such cases, the risk is expected to be higher if migrants came from a large non-purged population with high inbreeding load, particularly after the accumulation of the stochastic effects ascribed to repeated occasional migration events. Therefore, under the specific deleterious recessive mutation model considered, we conclude that additional caution should be taken in rescue programs. Unless the endangered population harbors some distinctive genetic singularity whose conservation is a main concern, restoration by continuous stable gene flow should be considered, whenever feasible, as it reduces the extinction risk compared to repeated occasional migration and can also allow recolonization events.

Quantifying the fraction of new mutations that are recessive lethal

“…This result implies a de novo mutation rate of ∼0.003 recessive lethal mutations per diploid human (assuming a lethal mutation rate of 0.5%) and ∼0.001 recessive lethal mutations per diploid fly (assuming a lethal mutation rate of 1%). Notably, when assuming 4-5% of new nonsynonymous mutations to be recessive lethal, as recently suggested (Kardos et al 2021; Pérez-Pereira, Caballero, and García-Dorado 2022), these models predict levels of segregating recessive lethals that are well above those observed empirically ( Fig. 7 ).…”

“…Specifically, available evidence suggests that the average number of segregating recessive lethal mutations in humans is roughly in the range of 0.6 to 1.6 per diploid (Gao et al 2015;Narasimhan et al 2016), and analytical predictions with <~0.5% of new nonsynonymous mutations being recessive lethal appear to approximate this range, regardless of the assumed effective population size. By contrast, analytical predictions with ~5% of new mutations being recessive lethal, a value that has recently been proposed (Kardos et al 2021;Pérez-Pereira, Caballero, and García-Dorado 2022), suggest ~10-20 recessive lethal mutations per diploid, well outside of empirical observations.…”

“…For example, Kardos et al (2021) proposed a DFE where 5% of deleterious mutations are recessive lethal and ∼21% have s < -0.1. Similarly, Pérez-Pereira, Caballero, and García-Dorado (2022) proposed a DFE with that ∼4% of deleterious mutations are recessive lethal, and ∼41% have s < -0.1. Importantly, both of these DFEs were not directly estimated from data, but were instead designed largely to reflect results from mutation accumulation experiments (Kardos et al 2021; Pérez-Pereira, Caballero, and García-Dorado 2022).…”

“…Similarly, Pérez-Pereira, Caballero, and García-Dorado (2022) proposed a DFE with that ∼4% of deleterious mutations are recessive lethal, and ∼41% have s < -0.1. Importantly, both of these DFEs were not directly estimated from data, but were instead designed largely to reflect results from mutation accumulation experiments (Kardos et al 2021; Pérez-Pereira, Caballero, and García-Dorado 2022). Other recent studies have focused on “nearly lethal” mutations, or those mutations that are not expected to segregate in a sample of genetic variation.…”

Genomic underpinnings of population persistence in Isle Royale moose

“…Purging may be most effective in populations where inbreeding is gradual due to a moderate population size (4)(5)(6)(9)(10)(11). However, the extent to which purging is a relevant factor for the conservation of threatened populations, and more broadly, the degree to which populations can persist with low genome-wide diversity, is controversial (9,(12)(13)(14)(15)(16)(17)(18).…”