bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2025–10–26
three papers selected by
Mariangela Santorsola, Università di Pavia



  1. PLoS One. 2025 ;20(10): e0335181
      Mitochondrial replacement therapy (MRT) presents a promising preventative measure to combat mitochondrial diseases. However, the long-term consequences of disrupting mitonuclear coevolution at both the molecular and organismal levels remain understudied. Data on sex-specific effects are also lacking despite predictions that males may be especially vulnerable to mitochondrial replacement. To address this, we used backcrossed lines of the copepod Tigriopus californicus to produce offspring with nuclear genotype contributions from two populations and a mitochondrial genotype from a third, separate, population. When compared to hybrid controls with mitochondrial genotypes that matched the maternal nuclear genotype but not the paternal, these "three-parent offspring" did not significantly differ in lifespan or routine metabolic rate. While these organismal-level traits showed no effect, molecular metrics of mitochondrial health revealed consequences of mitochondrial replacement. Oxidative DNA damage, measured by 8-hydroxy-2'-deoxyguanosine content, was higher in three-parent offspring, and mitochondrial DNA content was lower than in hybrid controls. While differences between sexes were present in some traits, sex did not interact with mitochondrial replacement for any of these metrics. Although these results could be due either to donor mitochondrial DNA matching neither of the nuclear parents, or to deficits in the donor mitochondrial DNA itself, they highlight the importance of considering molecular level consequences of mitochondrial replacement that may be masked at the organismal level when evaluating the health impacts of this treatment.
    DOI:  https://doi.org/10.1371/journal.pone.0335181
  2. J Evol Biol. 2025 Oct 20. pii: voaf127. [Epub ahead of print]
      Sequence variation in mitochondrial DNA was once considered neutral, but growing evidence indicates it can influence metabolic, physiological and life-history traits. Two hypotheses offer explanations for this non-neutral mtDNA variation: the mitochondrial climatic adaptation hypothesis, which posits that natural selection shapes mtDNA variation to match local environments, and the mother's curse hypothesis, which predicts the accumulation of male-harming variants due to maternal inheritance. We explored these hypotheses using genetic strains of Drosophila melanogaster bearing eight mtDNA haplotypes-nested within two distinct haplogroups (A1 and B1) that segregate along an Australian latitudinal cline. We measured the longevity of flies under cool (18 °C) and warm (28 °C) conditions, predicting that the A1 haplogroup-which has been reported to predominate at subtropical latitudes-would confer higher longevity in warm but reduced longevity in cool temperatures relative to the B1 counterpart. We also tested whether effects of mtDNA haplotype on longevity were larger in males, as predicted under the mother's curse hypothesis. We found mtDNA haplogroup and haplotype is associated with longevity, with the magnitude of effects varying with temperature, but not in a pattern consistent with either hypothesis. Haplogroup-by-environment interactions did not align with reported spatial distributions of the haplogroups, and haplotype effects on longevity were similar across sexes. Our findings add to the growing evidence that mtDNA variation contributes to thermal plasticity in longevity, but do not provide clear insight into whether this variation is adaptive or maladaptive.
    Keywords:  climatic adaptation; gene-by-environment; lifespan; mitochondrial haplotype; mitochondrial plasticity; mother’s curse; mtDNA; phenotypic plasticity; thermal stress
    DOI:  https://doi.org/10.1093/jeb/voaf127
  3. BMC Ecol Evol. 2025 Oct 23. 25(1): 112
      Mito-nuclear (or cytonuclear) discordance, evolutionary incongruence between the mitochondrial and nuclear genomes, is a widespread but underappreciated phenomenon that may obscure signals of introgression and hybridization important for understanding evolutionary trajectories and species boundaries. The present study explored the roles of secondary contact and introgressive hybridization in the diversification of Buthus Leach, 1815 scorpions in the Iberian Peninsula, a hotspot for mito-nuclear discordance, in which complex topography and glacial history facilitated repeated cycles of isolation and secondary contact. Patterns of mito-nuclear discordance were predicted to be consistent with overlapping distributions, similar ecological niches, and intermediate phenotypes. By integrating genomic, morphological, and ecological data, the intricate evolutionary history of Buthus, shaped by vicariance, reticulation and ecological opportunity, was revealed. The results underscore the role of introgressive hybridization in shaping patterns of biodiversity and the need to consider mito-nuclear discordance in species delimitation.
    Keywords:  Messinian salinity crisis; Pleistocene climatic oscillations; environmental niche modeling; genetic admixture; intermediate character combinations
    DOI:  https://doi.org/10.1186/s12862-025-02445-0