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bioRxiv · 10.64898/2025.12.16.694700

No molecular evidence for Muller's ratchet in mitochondrial genomes

Mo, Y. K.·Mishra, S. R.·Pena-Garcia, Y.·Hahn, M. W.
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Abstract

AO_SCPLOWBSTRACTC_SCPLOWMullers ratchet predicts that non-recombining genomes can accumulate deleterious mutations, though molecular evidence for it is rare. Previous studies have tried to detect ratchet-like behavior in mitochondria (mtDNA), contrasting the rate of nucleotide substitutions in mitochondrial transfer RNA (tRNA) genes with those in the nuclear genome. However, these studies relied on small datasets that could not control for the higher mutation rate in animal mtDNA. In this study, we re-evaluate evidence for Mullers ratchet with well-annotated mitochondrial and nuclear genomes from three species pairs. Across all three comparisons, mitochondrial tRNA (and protein-coding) genes are evolving under strong constraint, with dt/dS equal to 0.12 in primates, 0.07 in birds, and 0.04 in fruit flies. Compared with nuclear dt/dS, only the fruit fly comparison showed slightly lower constraint in mtDNA. Our results therefore provide evidence for strong, efficacious selection in animal mtDNA, with no ratchet-like accumulation of slightly deleterious mutations.

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Mo, Y. K., Mishra, S. R., Pena-Garcia, Y., Hahn, M. W.. 2025-12-16. No molecular evidence for Muller's ratchet in mitochondrial genomes. https://doi.org/10.64898/2025.12.16.694700

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