Conservation Mitonuclear Replacement: Facilitated mitochondrial adaptation for a changing world

Abstract

Most species will not be able to migrate fast enough to cope with climate change, nor evolve quickly enough with current levels of genetic variation. Exacerbating the problem are anthropogenic influences on adaptive potential, including the prevention of gene flow through habitat fragmentation and the erosion of genetic diversity in small, bottlenecked populations. Facilitated adaptation, or assisted evolution, offers a way to augment adaptive genetic variation via artificial selection, induced hybridization, or genetic engineering. One key source of genetic variation, particularly for climatic adaptation, are the core metabolic genes encoded by the mitochondrial genome. These genes influence environmental tolerance to heat, drought, and hypoxia, but must interact intimately and co-evolve with a suite of important nuclear genes. These coadapted mitonuclear genes form some of the important reproductive barriers between species. Mitochondrial genomes can and do introgress between species in an adaptive manner, and they may co-introgress with nuclear genes important for maintaining mitonuclear compatibility. Managers should consider the relevance of mitonuclear genetic variability in conservation decision-making, including as a tool for facilitating adaptation. I propose a novel technique dubbed Conservation Mitonuclear Replacement (CmNR), which entails replacing the core metabolic machinery of a threatened species-the mitochondrial genome and key nuclear loci-with those from a closely related species or a divergent population, which may be better-adapted to climatic changes or carry a lower genetic load. The most feasible route to CmNR is to combine CRISPR-based nuclear genetic editing with mitochondrial replacement and assisted reproductive technologies. This method preserves much of an organism's phenotype and could allow populations to persist in the wild when no other suitable conservation options exist. The technique could be particularly important on mountaintops, where rising temperatures threaten an alarming number of species with almost certain extinction in the next century.

Keywords: assisted evolution; climate change; conservation; facilitated adaptation; genetic rescue; mitochondria; mitonuclear interactions.

FIGURE 1

Three methods for introgressing mitochondrial genotypes while maintaining mitonuclear compatibility. The example species are the tropical Walian Ibex (Capra walie) as a mitochondrial donor and the endangered, temperate Western Tur (C. caucasica) as a recipient, which might benefit from a more warm‐adapted haplotype within its very limited range. To create a natural backcross hybrid (a), a female C. walie mt donor (green chromosomes; circular = mt, rectangular = nuclear) is introduced and naturally hybridizes with a wild male C. caucasica, creating F1 hybrids. These hybrids reproduce with themselves, creating F2 hybrids. Natural selection among F2 hybrids for mitonuclear compatibility, combined with backcrossing to parental‐species males, eventually creates hybrids with compatible N‐mt genes but with substantial tracts of donor nuclear (N) ancestry. To create an artificial backcross hybrid (b), initial F1 and subsequent F2 hybridization occurs in the lab, followed by artificial selection for hybrids not only with compatible mitonuclear genotypes but with minimal donor nuclear ancestry. To create a CmNR hybrid or “cybrid” (c), genetic editing and advanced reproductive technologies are used instead. A donor oocyte (large, green) is enucleated, removing its nucleus. A recipient somatic cell (small, orange) is edited at key N‐mt loci for mitonuclear compatibility. The somatic cell nucleus is then transferred into the membrane of the enucleated oocyte and fused by electroporation. The cybrid zygote is then implanted into a recipient species female for gestation. The resulting offspring have no donor species nuclear ancestry except at key compatibility loci that have been edited. Ibex drawings by Nat Jennings.

FIGURE 2

Three models applying Conservation Mitonuclear Replacement (CmNR) on isolated mountaintops. Species of differing colors are represented by mitochondrial genomes (rings) and nuclear genomes (paired rectangular chromosomes). Mountains at three latitudes have three elevational niches, each of differing temperatures at differing elevations: two below and one above some critical oxygen (O₂) threshold (dashed blue line). Mountains in the left column are in the present day, at roughly 1.5°C of committed warming above historical baseline temperatures, while mountains in the middle and right columns are in the future after 3°C of warming and depict outcomes with and without CmNR, respectively. (a) Competition avoidance: the blue temperate‐zone species is prevented from migrating upward with increasing temperatures by oxygen limitation above the O₂ threshold. CmNR introduces a mitogenome and N‐mt gene edits from a related species in the subtropics which lives higher and is adapted to the same temperatures, allowing the blue species to track rising temperatures. In the absence of CmNR, the blue species goes extinct because it fails to migrate past the oxygen barrier and is out‐competed by the orange species moving up from below. (b) Persistence‐in‐place: a subtropical species is prevented from migrating upwards to track temperatures because of a lack of higher‐elevation habitat on the mountain. CmNR from a related tropical species occurring at the same elevation allows persistence in the face of warming. In the absence of CmNR the species goes extinct due to unsuitable temperatures. (c) De novo engineering: a tropical species likewise is prevented from tracking temperatures due to a lack of high‐elevation habitat. No related species occurs at more‐tropical latitudes or warmer elevations. In the future, introduction of mt & N‐mt edits de novo might allow creation of a novel mitonuclear genotype better suited to warmer conditions. In the absence of CmNR the species goes extinct due to unsuitable temperatures.