Energy metabolism in species with Doubly Uniparental Inheritance (DUI) of mitochondria : investigating the functioning, maintenance and evolutionary relevance of a naturally heteroplasmic system

Mitochondria and their genome, the mitochondrial DNA (mtDNA), are usually transmitted only by the mother to both sons and daughters in metazoan (i.e. strict maternal inheritance, SMI). An exception to the general rule of SMI is found in around 100 species of bivalves, which are characterized by a doubly uniparental inheritance (DUI) of mitochondria. In DUI species, two highly divergent and sex-linked mtDNA lineages coexist. One mitochondrial lineage is maternally inherited (F-type) and is present in oocytes and somatic tissues of both female and male individuals. The other lineage is paternally inherited (M-type) and is present in sperm. In male somatic tissues both lineages sometimes coexist, a condition named heteroplasmy. Knowing that variations in mitochondrially-encoded genes might impact mitochondrial functions, and giving the strict association of M and F-type mtDNAs with different gametes, it is conceivable that the variation between the two DUI lineages might result in sex-specific bioenergetic adaptations with repercussion on reproduction. Despite providing an unprecedented opportunity for the mtDNA to evolve for male functions, the DUI system also brings the need for sperm mitochondria to preserve their genetic integrity, as well as for somatic cells to deal with heteroplasmy. The objective of my PhD was to link the mitochondrial genotype of DUI and SMI bivalve species to the phenotype. I explored the impact of sex-specific mtDNA variations upon a wide set of phenotypic traits, ranging from mitochondrial and cellular bioenergetics to sperm performance, investigating the adaptive value of DUI system in the light of reproductive fitness, mitochondrial selection, preservation and transmission.  The results stemming from this PhD project revealed a clear phenotypic divergence between DUI and SMI species, possibly reflecting the different selective pressures acting on their mitochondria as a result of their different mode of mitochondria transmission. Conversely to SMI species, the sex-specific evolution of DUI mtDNA variants results in the expression of different male and female bioenergetic phenotypes. At the level of mitochondrial functionality, M-type mitochondria exhibit a remodelled OXPHOS characterized by unusual respiratory control at the terminus of the respiratory chain. The general reorganization of DUI sperm bioenergetics also entails variation in the balance between the main energy producing pathways, including glycolysis, anaerobic glycolysis, fatty acid metabolism, tricarboxylic acid cycle, OXPHOS, as well as the antioxidant capacity. Finally, DUI sperm exhibit an unusual motility phenotype characterized by slow speed and high curvilinear trajectory, traits potentially associated with a higher reproductive success in sessile broadcast spawning marine organisms. They also completely rely on the energy produced by OXPHOS to sustain their performance, although maintaining the ability to switch to a more combined aerobic/anaerobic strategy of energy production after oocyte detection. Altogether, these results suggest that the mtDNA variation in DUI species might be adaptive, resulting in the expression of sex-specific bioenergetic adaptation with downstream effect on sperm performance, reproductive fitness, paternal mitochondria selection, preservation and transmission. The results also suggest that heteroplasmy has an impact onto the bioenergetics of male soma, and that a functional compensation between genomes might minimize any potential deleterious outcome.

Keyphrases: DUI, SMI, Bivalves, OXPHOS, Mitochondria, Gametes, Heteroplasmy, Energy metabolism, Mitonuclear coevolution