Duplicated Energy Genes Reveal How Fish Mitochondria Evolved After Genome Doubling

Every heartbeat, every twitch of a fin, and every dividing cell in a fish embryo depends on a molecular machine so ancient that its origins trace back billions of years. Oxidative phosphorylation, or OXPHOS, is the process by which cells convert nutrients into adenosine triphosphate, the universal energy currency of life. This system generates more than 90 percent of the ATP in a typical cell, and it is built from five multiprotein complexes embedded in the inner mitochondrial membrane. Remarkably, these complexes are assembled from components encoded by two separate genomes: the small mitochondrial genome inherited maternally and the much larger nuclear genome contributed by both parents. A new study published in BMC Genomics has now provided the first comprehensive picture of how the nuclear-encoded portion of this essential machinery has evolved in one of the most species-rich groups of vertebrates on Earth, the euteleost fishes.

The research, led by Andreas Tsipourlianos and Katerina A. Moutou of the University of Thessaly in Greece, together with João C. R. Cardoso and Deborah M. Power of the University of the Algarve in Portugal, focused on two fish species of enormous commercial importance in Mediterranean aquaculture: the gilthead seabream (Sparus aurata) and the European seabass (Dicentrarchus labrax). These species are evolutionarily close relatives, yet they occupy ecologically distinct niches, making them an ideal comparative pair for dissecting how genome history and ecological lifestyle interact to shape the genetic architecture of core metabolism. Both species also possess well-annotated reference genomes, a prerequisite for the kind of rigorous comparative genomics the team undertook.

Teleost fishes carry a particularly rich evolutionary legacy in their DNA. Like all vertebrates, their ancestors experienced two rounds of whole-genome duplication deep in evolutionary time. Then, roughly 350 million years ago, the lineage that gave rise to modern teleosts underwent a third, teleost-specific genome duplication. These events doubled and redoubled the genetic raw material available to fish ancestors, creating thousands of duplicate gene pairs. Most duplicates are eventually lost, silenced by mutation, or repurposed for new functions. But some are retained, and understanding why certain duplicates persist while others vanish is one of the central questions in genome evolution. OXPHOS genes, with their tight dosage requirements and dual-genome coordination, represent an especially demanding test case for theories of duplicate retention.

Using comparative genomics across euteleost lineages, the researchers identified 23 multi-copy OXPHOS gene families in the gilthead seabream and 21 in the European seabass. This means that for a substantial number of the genes encoding the respiratory machinery, both fish carry more than one copy, or paralogue, in their nuclear genomes. Critically, the team was able to trace the origin of most of these duplicated families back to the teleost-specific genome duplication, demonstrating that this ancient genomic upheaval left a durable imprint on one of the most conserved metabolic pathways in biology. The finding challenges any assumption that core energy genes are immune to the effects of genome doubling.

Why would an organism keep two copies of a gene whose product must be produced in precise stoichiometric proportions to assemble a functional respiratory complex? The researchers tested a hypothesis that has gained traction in evolutionary biology: duplicate retention reflects a balance between dosage constraints, which favor keeping both copies active at reduced levels to maintain the correct overall output, and functional divergence, which allows one copy to specialize in a new context, tissue, or developmental stage. To examine this balance in action, the team turned to a life stage where energy demand is at its most extreme: early larval development.

Fish larvae are biological sprinters. Within days of hatching, they must grow rapidly, develop organs, begin swimming and feeding, and reorganize their metabolism from the yolk-dependent state of the embryo to the self-fueling physiology of a free-living organism. Mitochondrial energy production is central to every one of these transitions, and any disruption to OXPHOS function during this window can be lethal. This makes early development an ideal natural experiment for asking whether duplicated OXPHOS genes do the same work or different work.

The transcriptomics analysis revealed that paralogous OXPHOS genes do not behave uniformly. Some paralogues showed stable, coordinated expression patterns across development, consistent with the dosage-balance model: both copies contribute to maintaining the required output of the respiratory complexes. Others displayed a strikingly different behavior, being expressed only at specific developmental stages, suggesting that they have acquired stage-specific regulatory roles. This split personality among duplicates, with some copies serving as dosage partners and others as developmental specialists, provides direct evidence that functional diversification has shaped the OXPHOS repertoire of these fish since the teleost genome duplication.

The implications extend beyond evolutionary theory. Aquaculture is one of the fastest-growing food production sectors in the world, and gilthead seabream and European seabass are cornerstone species of Mediterranean fish farming. Larval survival is a persistent bottleneck in hatchery production, and energy metabolism is a key determinant of whether a larva successfully navigates the vulnerable early stages of life. By mapping which OXPHOS paralogues are deployed at which developmental moments, the study lays a molecular foundation for understanding, and potentially improving, larval performance under farming conditions. Genes that are switched on during critical developmental transitions could serve as markers of metabolic health or as targets for nutritional and environmental optimization.

The work also speaks to a broader question in biology: how do the mitochondrial and nuclear genomes, which are inherited in different ways and evolve at different rates, maintain their intricate partnership across hundreds of millions of years? Duplicated nuclear OXPHOS genes add another layer of complexity to this coevolutionary dance. If one nuclear copy diverges in function or expression, the mitochondrial components with which it interacts must remain compatible. The retention patterns documented in seabream and seabass suggest that this negotiation has produced a flexible but carefully balanced system, one in which redundancy provides resilience and specialization provides developmental precision.

Funding for the study came from the European Union through the H2020 PerformFISH project, which aims to integrate innovative approaches for competitive and sustainable performance across the Mediterranean aquaculture value chain, along with Portuguese national funds from the Foundation for Science and Technology. Larval samples were supplied by the Hellenic Centre for Marine Research in Crete, whose certified aquaculture facilities enabled the controlled developmental work underpinning the transcriptomic analysis. As the first comprehensive survey of OXPHOS paralogue evolution in euteleosts, the study opens a window onto how ancient genome doublings continue to echo through the metabolism of modern fish, and it suggests that the duplicated genes left behind by those events are not evolutionary leftovers but active, functionally relevant players in the energy economy of development. For a pathway as fundamental as oxidative phosphorylation, that flexibility may be exactly what allowed teleosts, the most diverse group of vertebrates, to radiate into nearly every aquatic habitat on the planet.

Subject of Research: Evolution and retention of duplicated oxidative phosphorylation genes in euteleost fishes

Article Title: Evolution and retention of oxidative phosphorylation paralogues in euteleosts: insights from gilthead seabream and European seabass

Article References: Tsipourlianos, A., Cardoso, J. C. R., Angelakopoulos, R., Kotoula, A., Power, D. M., Mamuris, Z., & Moutou, K. A. (2026). Evolution and retention of oxidative phosphorylation paralogues in euteleosts: insights from gilthead seabream and European seabass. BMC Genomics. https://doi.org/10.1186/s12864-026-13338-x

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13338-x

Keywords: oxidative phosphorylation, OXPHOS, gene duplication, teleost genome duplication, gilthead seabream, European seabass, mitochondria, larval development, comparative genomics, transcriptomics, gene retention, aquaculture