Yu-Chi Chen1,2, David L.J. Vendrami3,4,5,6, Maximilian L. Huber2, Luisa E.Y. Handel2, Christopher R. Cooney7, Joseph I. Hoffman3,4,5,6,8 and Toni I. Gossmann1,2,3,5 1Computational Systems Biology, Faculty of Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, Germany; 2Department of Evolutionary Genetics, Faculty of Biology, Bielefeld University, 33615 Bielefeld, Germany; 3Department of Animal Behavior, Faculty of Biology, Bielefeld University, 33615 Bielefeld, Germany; 4Department of Evolutionary Population Genetics, Faculty of Biology, Bielefeld University, 33501 Bielefeld, Germany; 5Joint Institute for Individualization in a Changing Environment (JICE), Bielefeld University and University of Münster, 48149 Münster, Germany; 6Center for Biotechnology (CeBiTec), Faculty of Biology, Bielefeld University, 33615 Bielefeld, Germany; 7Ecology and Evolutionary Biology, School of Biosciences, University of Sheffield, Sheffield S10 2TN, United Kingdom; 8British Antarctic Survey, High Cross, Cambridge CB3 OET, United Kingdom Corresponding author: toni.gossmanntu-dortmund.de Abstract

Sporadically, genetic material that originates from an organelle genome integrates into the nuclear genome. However, it is unclear what processes maintain such integrations over evolutionary time. Recently, it was shown that nuclear DNA of mitochondrial origin (NUMT) may harbor genes with intact mitochondrial reading frames despite the fact that they are highly divergent from the host's mitochondrial genome. Two major hypotheses have been put forward to explain the existence of such mitocoding nuclear genes: (1) recent introgression from another species and (2) long-term selection. To investigate whether these intriguing possibilities play a role, we scanned the genomes of more than 1000 avian and mammalian species for NUMTs. We show that a subclass of divergent NUMTs harboring mitogenes with intact reading frames is widespread across mammals and birds. We also show that some of these NUMTs appear to be similar across species. In addition, we demonstrate that many mitochondrial-coding NUMTs exhibit signs of long-term selection. In a subset of these NUMT genes, we detected evolutionary signals consistent with adaptive evolution, including one human NUMT shared among seven ape species. These findings suggest that NUMT insertions may occasionally be functional.

Received April 3, 2024. Accepted March 20, 2025.