Why the DNA‐containing organelles, chloroplasts, and mitochondria, are inherited maternally is a long standing and unsolved question. However, recent years have seen a paradigm shift, in that the absoluteness of uniparental inheritance is increasingly questioned. Here, we review the field and propose a unifying model for organelle inheritance. We argue that the predominance of the maternal mode is a result of higher mutational load in the paternal gamete. Uniparental inheritance evolved from relaxed organelle inheritance patterns because it avoids the spread (...) of selfish cytoplasmic elements. However, on evolutionary timescales, uniparentally inherited organelles are susceptible to mutational meltdown (Muller's ratchet). To prevent this, fall‐back to relaxed inheritance patterns occurs, allowing low levels of sexual organelle recombination. Since sexual organelle recombination is insufficient to mitigate the effects of selfish cytoplasmic elements, various mechanisms for uniparental inheritance then evolve again independently. Organelle inheritance must therefore be seen as an evolutionary unstable trait, with a strong general bias to the uniparental, maternal, mode. (shrink)

Many conserved eukaryotic traits, including apoptosis, two sexes, speciation and ageing, can be causally linked to a bioenergetic requirement for mitochondrial genes. Mitochondrial genes encode proteins involved in cell respiration, which interact closely with proteins encoded by nuclear genes. Functional respiration requires the coadaptation of mitochondrial and nuclear genes, despite divergent tempi and modes of evolution. Free‐radical signals emerge directly from the biophysics of mosaic respiratory chains encoded by two genomes prone to mismatch, with apoptosis being the default penalty for (...) compromised respiration. Selection for genomic matching is facilitated by two sexes, and optimizes fitness, adaptability and fertility in youth. Mismatches cause infertility, low fitness, hybrid breakdown, and potentially speciation. The dynamics of selection for mitonuclear function optimize fitness over generations, but the same selective processes also operate within generations, driving ageing and age‐related diseases. This coherent view of eukaryotic energetics offers striking insights into infertility and age‐related diseases. (shrink)