The mitochondria contain their own genome derived from an alphaproteobacterial endosymbiont. From thousands of protein-coding genes originally encoded by their ancestor, only between 1 and about 70 are encoded on extant mitochondrial genomes (mitogenomes). Thanks to a dramatically increasing number of sequenced and annotated mitogenomes a coherent picture of why some genes were lost, or relocated to the nucleus, is emerging. In this review, we describe the characteristics of mitochondria-to-nucleus gene transfer and the resulting varied content of mitogenomes across eukaryotes. We introduce a 'burst-upon-drift' model to best explain nuclear-mitochondrial population genetics with flares of transfer due to genetic drift.

Center for Mechanisms of Evolution Biodesign Institute School of Life Sciences Arizona State University Tempe USA

Faculty of Science University of Ostrava Ostrava Czech Republic

Faculty of Sciences University of South Bohemia České Budějovice Czech Republic

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic

Medical Biochemistry Amsterdam UMC University of Amsterdam Amsterdam The Netherlands

See more in PubMed

Roger AJ, Munoz-Gomez SA, Kamikawa R. The origin and diversification of mitochondria. Curr Biol. 2017;27(21):R1177–R1192. doi: 10.1016/j.cub.2017.09.015. PubMed DOI

Strassert JFH, Irisarri I, Williams TA, Burki F. A molecular timescale for eukaryote evolution with implications for the origin of red algal-derived plastids. Nat Commun. 2021;12(1):1879. doi: 10.1038/s41467-021-22044-z. PubMed DOI PMC

Al Jewari C, Baldauf SL. An excavate root for the eukaryote tree of life. Sci Adv. 2023;9(17):eade4973. doi: 10.1126/sciadv.ade4973. PubMed DOI PMC

Burger G, Gray MW, Forget L, Lang BF. Strikingly bacteria-like and gene-rich mitochondrial genomes throughout jakobid protists. Genome Biol Evol. 2013;5(2):418–438. doi: 10.1093/gbe/evt008. PubMed DOI PMC

Janouškovec J, Tikhonenkov DV, Burki F, Howe AT, Rohwer FL, Mylnikov AP, Keeling PJ. A new lineage of eukaryotes illuminates early mitochondrial genome reduction. Curr Biol. 2017;27(23):3717–3724.e3715. doi: 10.1016/j.cub.2017.10.051. PubMed DOI

Kelly S. The economics of organellar gene loss and endosymbiotic gene transfer. Genome Biol. 2021;22(1):345. doi: 10.1186/s13059-021-02567-w. PubMed DOI PMC

García Pascual B, Nordbotten JM, Johnston IG. Cellular and environmental dynamics influence species-specific extents of organelle gene retention. Proc Royal Soc B: Biol Sci. 1994;2023(290):20222140. PubMed PMC

Nowack ECM, Grossman AR. Trafficking of protein into the recently established photosynthetic organelles of Paulinella chromatophora. Proc Natl Acad Sci. 2012;109(14):5340–5345. doi: 10.1073/pnas.1118800109. PubMed DOI PMC

Tice AK, Žihala D, Pánek T, Jones RE, Salomaki ED, Nenarokov S, Burki F, Eliáš M, Eme L, Roger AJ, et al. PhyloFisher: a phylogenomic package for resolving eukaryotic relationships. PLoS Biol. 2021;19(8):e3001365. doi: 10.1371/journal.pbio.3001365. PubMed DOI PMC

Tikhonenkov DV, Jamy M, Borodina AS, Belyaev AO, Zagumyonnyi DG, Prokina KI, Mylnikov AP, Burki F, Karpov SA. On the origin of TSAR: morphology, diversity and phylogeny of Telonemia. Open Biol. 2022;12(3):210325. doi: 10.1098/rsob.210325. PubMed DOI PMC

Field HI, Coulson RMR, Field MC. An automated graphics tool for comparative genomics: the Coulson plot generator. BMC Bioinformatics. 2013;14(1):141. doi: 10.1186/1471-2105-14-141. PubMed DOI PMC

Gray MW, Burger G, Lang BF. Mitochondrial evolution. Science. 1999;283(5407):1476–1481. doi: 10.1126/science.283.5407.1476. PubMed DOI

Martijn J, Vosseberg J, Guy L, Offre P, Ettema TJG. Deep mitochondrial origin outside the sampled alphaproteobacteria. Nature. 2018;557(7703):101–105. doi: 10.1038/s41586-018-0059-5. PubMed DOI

Berg OG, Kurland CG. Why mitochondrial genes are most often found in nuclei. Mol Biol Evol. 2000;17(6):951–961. doi: 10.1093/oxfordjournals.molbev.a026376. PubMed DOI

Speijer D. How mitochondria showcase evolutionary mechanisms and the importance of oxygen. Bioessays. 2023;45(6):e2300013. PubMed

John U, Lu Y, Wohlrab S, Groth M, Janouškovec J, Kohli GS, Mark FC, Bickmeyer U, Farhat S, Felder M, et al. An aerobic eukaryotic parasite with functional mitochondria that likely lacks a mitochondrial genome. Sci Adv. 2019;5(4):eaav1110. doi: 10.1126/sciadv.aav1110. PubMed DOI PMC

Kayal E, Smith DR. Is the dinoflagellate Amoebophrya really missing an mtDNA? Mol Biol Evol. 2021;38(6):2493–2496. doi: 10.1093/molbev/msab041. PubMed DOI PMC

Farhat S, Le P, Kayal E, Noel B, Bigeard E, Corre E, Maumus F, Florent I, Alberti A, Aury J-M, et al. Rapid protein evolution, organellar reductions, and invasive intronic elements in the marine aerobic parasite dinoflagellate Amoebophrya spp. BMC Biol. 2021;19(1):1. doi: 10.1186/s12915-020-00927-9. PubMed DOI PMC

Giannakis K, Arrowsmith SJ, Richards L, Gasparini S, Chustecki JM, Røyrvik EC, Johnston IG. Evolutionary inference across eukaryotes identifies universal features shaping organelle gene retention. Cell Syst. 2022;13(11):874–884.e875. doi: 10.1016/j.cels.2022.08.007. PubMed DOI

Johnston IG, Williams BP. Evolutionary inference across eukaryotes identifies specific pressures favoring mitochondrial gene retention. Cell Syst. 2016;2(2):101–111. doi: 10.1016/j.cels.2016.01.013. PubMed DOI

Allen JF. Why chloroplasts and mitochondria retain their own genomes and genetic systems: colocation for redox regulation of gene expression. Proc Natl Acad Sci U S A. 2015;112(33):10231–10238. doi: 10.1073/pnas.1500012112. PubMed DOI PMC

Allen JF. The CoRR hypothesis for genes in organelles. J Theor Biol. 2017;434:50–57. doi: 10.1016/j.jtbi.2017.04.008. PubMed DOI

Grub LK, Tsyba N, Patel MR. Should I stay, or should I go? Gene retention in organellar genomes. Cell Syst. 2022;13(11):861–863. doi: 10.1016/j.cels.2022.10.006. PubMed DOI

Blanchard JL, Lynch M. Organellar genes: why do they end up in the nucleus? Trends Genet. 2000;16(7):315–320. doi: 10.1016/S0168-9525(00)02053-9. PubMed DOI

Oborník M, Lukeš J. The organellar genomes of Chromera and Vitrella, the phototrophic relatives of Apicomplexan parasites. Annu Rev Microbiol. 2015;69(1):129–144. doi: 10.1146/annurev-micro-091014-104449. PubMed DOI

Anderson S, Bankier AT, Barrell BG, de Bruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981;290(5806):457–465. doi: 10.1038/290457a0. PubMed DOI

Gray MW, Lang BF, Burger G. Mitochondria of protists. Annu Rev Genet. 2004;38:477–524. doi: 10.1146/annurev.genet.37.110801.142526. PubMed DOI

Warren JM, Salinas-Giegé T, Triant DA, Taylor DR, Drouard L, Sloan DB. Rapid shifts in mitochondrial tRNA import in a plant lineage with extensive mitochondrial tRNA gene loss. Mol Biol Evol. 2021;38(12):5735–5751. doi: 10.1093/molbev/msab255. PubMed DOI PMC

Warren JM, Broz AK, Martinez-Hottovy A, Elowsky C, Christensen AC, Sloan DB. Rewiring of aminoacyl-tRNA synthetase localization and interactions in plants with extensive mitochondrial tRNA gene loss. Mol Biol Evol. 2023;40(7):msad163. PubMed PMC

Lang BF, Burger G, O’Kelly CJ, Cedergren R, Golding GB, Lemieux C, Sankoff D, Turmel M, Gray MW. An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature. 1997;387(6632):493–497. doi: 10.1038/387493a0. PubMed DOI

Pawlowski J, Audic S, Adl S, Bass D, Belbahri L, Berney C, Bowser SS, Cepicka I, Decelle J, Dunthorn M, et al. CBOL Protist Working Group: barcoding eukaryotic richness beyond the animal, plant, and fungal kingdoms. PLoS Biol. 2012;10(11):e1001419. doi: 10.1371/journal.pbio.1001419. PubMed DOI PMC

Burki F, Roger AJ, Brown MW, Simpson AGB. The new tree of eukaryotes. Trends Ecol Evol. 2020;35(1):43–55. doi: 10.1016/j.tree.2019.08.008. PubMed DOI

Janouškovec J, Tikhonenkov DV, Mikhailov KV, Simdyanov TG, Aleoshin VV, Mylnikov AP, Keeling PJ. Colponemids represent multiple ancient alveolate lineages. Curr Biol. 2013;23(24):2546–2552. doi: 10.1016/j.cub.2013.10.062. PubMed DOI

Lax G, Eglit Y, Eme L, Bertrand EM, Roger AJ, Simpson AGB. Hemimastigophora is a novel supra-kingdom-level lineage of eukaryotes. Nature. 2018;564(7736):410–414. doi: 10.1038/s41586-018-0708-8. PubMed DOI

Gawryluk RMR, Tikhonenkov DV, Hehenberger E, Husnik F, Mylnikov AP, Keeling PJ. Non-photosynthetic predators are sister to red algae. Nature. 2019;572(7768):240–243. doi: 10.1038/s41586-019-1398-6. PubMed DOI

Tikhonenkov DV, Strassert JFH, Janouškovec J, Mylnikov AP, Aleoshin VV, Burki F, Keeling PJ. Predatory colponemids are the sister group to all other alveolates. Mol Phylogenet Evol. 2020;149:106839. doi: 10.1016/j.ympev.2020.106839. PubMed DOI

Bykov YS, Flohr T, Boos F, Zung N, Herrmann JM, Schuldiner M. Widespread use of unconventional targeting signals in mitochondrial ribosome proteins. EMBO J. 2022;41(1):e109519. doi: 10.15252/embj.2021109519. PubMed DOI PMC

Macher J-N, Coots NL, Poh Y-P, Girard EB, Langerak A, Muñoz-Gómez SA, Sinha SD, Jirsová D, Vos R, Wissels R, et al. Single-cell genomics reveals the divergent mitochondrial genomes of Retaria (Foraminifera and Radiolaria) mBio. 2023;14(2):e00302–00323. doi: 10.1128/mbio.00302-23. PubMed DOI PMC

Kamikawa R, Inagaki Y, Sako Y. Fragmentation of mitochondrial large subunit rRNA in the dinoflagellate Alexandrium catenella and the evolution of rRNA structure in alveolate mitochondria. Protist. 2007;158(2):239–245. doi: 10.1016/j.protis.2006.12.002. PubMed DOI

Slamovits CH, Saldarriaga JF, Larocque A, Keeling PJ. The highly reduced and fragmented mitochondrial genome of the early-branching dinoflagellate Oxyrrhis marina shares characteristics with both apicomplexan and dinoflagellate mitochondrial genomes. J Mol Biol. 2007;372(2):356–368. doi: 10.1016/j.jmb.2007.06.085. PubMed DOI

Valach M, Moreira S, Kiethega GN, Burger G. Trans-splicing and RNA editing of LSU rRNA in Diplonema mitochondria. Nucleic Acids Res. 2014;42(4):2660–2672. doi: 10.1093/nar/gkt1152. PubMed DOI PMC

Feagin JE, Harrell MI, Lee JC, Coe KJ, Sands BH, Cannone JJ, Tami G, Schnare MN, Gutell RR. The fragmented mitochondrial ribosomal RNAs of Plasmodium falciparum. PLoS ONE. 2012;7(6):e38320. doi: 10.1371/journal.pone.0038320. PubMed DOI PMC

Martin W, Herrmann RG. Gene transfer from organelles to the nucleus: how much, what happens, and why?1. Plant Physiol. 1998;118(1):9–17. doi: 10.1104/pp.118.1.9. PubMed DOI PMC

Allen JF, Raven JA. Free-radical-induced mutation vs redox regulation: costs and benefits of genes in organelles. J Mol Evol. 1996;42(5):482–492. doi: 10.1007/BF02352278. PubMed DOI

Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1–13. doi: 10.1042/BJ20081386. PubMed DOI PMC

Speijer D. Birth of the eukaryotes by a set of reactive innovations: new insights force us to relinquish gradual models. BioEssays. 2015;37(12):1268–1276. doi: 10.1002/bies.201500107. PubMed DOI

Lynch M. The evolution of multimeric protein assemblages. Mol Biol Evol. 2011;29(5):1353–1366. doi: 10.1093/molbev/msr300. PubMed DOI PMC

Lynch M. Evolutionary layering and the limits to cellular perfection. Proc Natl Acad Sci. 2012;109(46):18851–18856. doi: 10.1073/pnas.1216130109. PubMed DOI PMC

Richly E, Leister D. NUMTs in sequenced eukaryotic genomes. Mol Biol Evol. 2004;21(6):1081–1084. doi: 10.1093/molbev/msh110. PubMed DOI

Brennicke A, Grohmann L, Hiesel R, Knoop V, Schuster W. The mitochondrial genome on its way to the nucleus: different stages of gene transfer in higher plants. FEBS Lett. 1993;325(1–2):140–145. doi: 10.1016/0014-5793(93)81430-8. PubMed DOI

Adams KL, Palmer JD. Evolution of mitochondrial gene content: gene loss and transfer to the nucleus. Mol Phylogenet Evol. 2003;29(3):380–395. doi: 10.1016/S1055-7903(03)00194-5. PubMed DOI

Pont-Kingdon G, Okada NA, Macfarlane JL, Beagley CT, Watkins-Sims CD, Cavalier-Smith T, Clark-Walker GD, Wolstenholme DR. Mitochondrial DNA of the coral Sarcophyton glaucum contains a gene for a homologue of bacterial muts: a possible case of gene transfer from the nucleus to the mitochondrion. J Mol Evol. 1998;46(4):419–431. doi: 10.1007/PL00006321. PubMed DOI

Bilewitch JP, Degnan SM. A unique horizontal gene transfer event has provided the octocoral mitochondrial genome with an active mismatch repair gene that has potential for an unusual self-contained function. BMC Evol Biol. 2011;11:228. doi: 10.1186/1471-2148-11-228. PubMed DOI PMC

Milner DS, Wideman JG, Stairs CW, Dunn CD, Richards TA. A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist. PLoS Biol. 2021;19(4):e3001126. doi: 10.1371/journal.pbio.3001126. PubMed DOI PMC

de Grey AD. Forces maintaining organellar genomes: is any as strong as genetic code disparity or hydrophobicity? BioEssays. 2005;27(4):436–446. doi: 10.1002/bies.20209. PubMed DOI

Timmis JN, Ayliffe MA, Huang CY, Martin W. Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat Rev Genet. 2004;5(2):123–135. doi: 10.1038/nrg1271. PubMed DOI

Wei W, Schon KR, Elgar G, Orioli A, Tanguy M, Giess A, Tischkowitz M, Caulfield MJ, Chinnery PF. Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes. Nature. 2022;611(7934):105–114. doi: 10.1038/s41586-022-05288-7. PubMed DOI PMC

Kleine T, Maier UG, Leister D. DNA transfer from organelles to the nucleus: the idiosyncratic genetics of endosymbiosis. Annu Rev Plant Biol. 2009;60(1):115–138. doi: 10.1146/annurev.arplant.043008.092119. PubMed DOI

Kadowaki K, Kubo N, Ozawa K, Hirai A. Targeting presequence acquisition after mitochondrial gene transfer to the nucleus occurs by duplication of existing targeting signals. EMBO J. 1996;15(23):6652–6661. doi: 10.1002/j.1460-2075.1996.tb01055.x. PubMed DOI PMC

Pérez-Martínez X, Vazquez-Acevedo M, Tolkunova E, Funes S, Claros MG, Davidson E, King MP, González-Halphen D. Unusual location of a mitochondrial gene. Subunit III of cytochrome C oxidase is encoded in the nucleus of Chlamydomonad algae. J Biol Chem. 2000;275(39):30144–30152. PubMed

Ojaimi J, Pan J, Santra S, Snell WJ, Schon EA. An algal nucleus-encoded subunit of mitochondrial ATP synthase rescues a defect in the analogous human mitochondrial-encoded subunit. Mol Biol Cell. 2002;13(11):3836–3844. doi: 10.1091/mbc.e02-05-0306. PubMed DOI PMC

Figueroa-Martinez F, Vazquez-Acevedo M, Cortes-Hernandez P, Garcia-Trejo JJ, Davidson E, King MP, Gonzalez-Halphen D. What limits the allotopic expression of nucleus-encoded mitochondrial genes? The case of the chimeric Cox3 and Atp6 genes. Mitochondrion. 2011;11(1):147–154. doi: 10.1016/j.mito.2010.09.003. PubMed DOI

Boominathan A, Vanhoozer S, Basisty N, Powers K, Crampton AL, Wang X, Friedricks N, Schilling B, Brand MD, O’Connor MS. Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA complex V null mutant. Nucleic Acids Res. 2016;44(19):9342–9357. PubMed PMC

Bietenhader M, Martos A, Tetaud E, Aiyar RS, Sellem CH, Kucharczyk R, Clauder-Münster S, Giraud M-F, Godard F, Salin B, et al. Experimental relocation of the mitochondrial ATP9 gene to the nucleus reveals forces underlying mitochondrial genome evolution. PLoS Genet. 2012;8(8):e1002876. doi: 10.1371/journal.pgen.1002876. PubMed DOI PMC

Nagley P, Farrell LB, Gearing DP, Nero D, Meltzer S, Devenish RJ. Assembly of functional proton-translocating ATPase complex in yeast mitochondria with cytoplasmically synthesized subunit 8, a polypeptide normally encoded within the organelle. Proc Natl Acad Sci U S A. 1988;85(7):2091–2095. doi: 10.1073/pnas.85.7.2091. PubMed DOI PMC

Supekova L, Supek F, Greer JE, Schultz PG. A single mutation in the first transmembrane domain of yeast COX2 enables its allotopic expression. Proc Natl Acad Sci. 2010;107(11):5047–5052. doi: 10.1073/pnas.1000735107. PubMed DOI PMC

Claros MG, Perea J, Shu Y, Samatey FA, Popot JL, Jacq C. Limitations to in vivo import of hydrophobic proteins into yeast mitochondria. The case of a cytoplasmically synthesized apocytochrome b. Eur J Biochem. 1995;228(3):762–771. PubMed

Mathur V, Wakeman KC, Keeling PJ. Parallel functional reduction in the mitochondria of apicomplexan parasites. Curr Biol. 2021;31(13):2920–2928.e2924. doi: 10.1016/j.cub.2021.04.028. PubMed DOI

Prokopchuk G, Butenko A, Dacks JB, Speijer D, Field MC, Lukeš J. Lessons from the deep: mechanisms behind the diversification of eukaryotic protein complexes. Biol Rev. 2023;98(6):1910–27. PubMed PMC

Popot JL, de Vitry C. On the microassembly of integral membrane proteins. Annu Rev Biophys Biophys Chem. 1990;19:369–403. doi: 10.1146/annurev.bb.19.060190.002101. PubMed DOI

Heijne G. The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology. EMBO J. 1986;5(11):3021–3027. doi: 10.1002/j.1460-2075.1986.tb04601.x. PubMed DOI PMC

Björkholm P, Harish A, Hagström E, Ernst AM, Andersson SGE. Mitochondrial genomes are retained by selective constraints on protein targeting. Proc Natl Acad Sci. 2015;112(33):10154–10161. doi: 10.1073/pnas.1421372112. PubMed DOI PMC

Björkholm P, Ernst AM, Hagström E, Andersson SGE. Why mitochondria need a genome revisited. FEBS Lett. 2017;591(1):65–75. doi: 10.1002/1873-3468.12510. PubMed DOI

Flegontov P, Michálek J, Janouškovec J, Lai D-H, Jirků M, Hajdušková E, Tomčala A, Otto TD, Keeling PJ, Pain A, et al. Divergent mitochondrial respiratory chains in phototrophic relatives of apicomplexan parasites. Mol Biol Evol. 2015;32(5):1115–1131. doi: 10.1093/molbev/msv021. PubMed DOI

Daley DO, Whelan J. Why genes persist in organelle genomes. Genome Biol. 2005;6(5):110. doi: 10.1186/gb-2005-6-5-110. PubMed DOI PMC

Gawryluk RMR, Kamikawa R, Stairs CW, Silberman JD, Brown MW, Roger AJ. The earliest stages of mitochondrial adaptation to low oxygen revealed in a novel rhizarian. Curr Biol. 2016;26(20):2729–2738. doi: 10.1016/j.cub.2016.08.025. PubMed DOI

Pyrih J, Pánek T, Durante IM, Rašková V, Cimrhanzlová K, Kriegová E, Tsaousis AD, Eliáš M, Lukeš J. Vestiges of the bacterial signal recognition particle-based protein targeting in mitochondria. Mol Biol Evol. 2021;38(8):3170–3187. doi: 10.1093/molbev/msab090. PubMed DOI PMC

Daley DO, Clifton R, Whelan J. Intracellular gene transfer: reduced hydrophobicity facilitates gene transfer for subunit 2 of cytochrome c oxidase. Proc Natl Acad Sci U S A. 2002;99(16):10510–10515. doi: 10.1073/pnas.122354399. PubMed DOI PMC

Allen JF. Control of gene expression by redox potential and the requirement for chloroplast and mitochondrial genomes. J Theor Biol. 1993;165(4):609–631. doi: 10.1006/jtbi.1993.1210. PubMed DOI

Liu X, Shan G. Mitochondria encoded non-coding RNAs in cell physiology. Front Cell Dev Biol. 2021;9:713729. PubMed PMC

Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Abeta. Proc Natl Acad Sci U S A. 2001;98(11):6336–6341. doi: 10.1073/pnas.101133498. PubMed DOI PMC

Wang Y, Li N, Zeng Z, Tang L, Zhao S, Zhou F, Zhou L, Xia W, Zhu C, Rao M. Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway. Mol Human Reprod. 2020;27(2):gaaa081. PubMed

Herrmann JM, Woellhaf MW, Bonnefoy N. Control of protein synthesis in yeast mitochondria: the concept of translational activators. Biochim Biophys Acta. 2013;1833(2):286–294. doi: 10.1016/j.bbamcr.2012.03.007. PubMed DOI

Allen JF. Separate sexes and the mitochondrial theory of ageing. J Theor Biol. 1996;180(2):135–140. doi: 10.1006/jtbi.1996.0089. PubMed DOI

Hancock K, Hajduk SL. The mitochondrial tRNAs of Trypanosoma brucei are nuclear encoded. J Biol Chem. 1990;265(31):19208–19215. doi: 10.1016/S0021-9258(17)30645-2. PubMed DOI

Kaur B, Záhonová K, Valach M, Faktorová D, Prokopchuk G, Burger G, Lukeš J. Gene fragmentation and RNA editing without borders: eccentric mitochondrial genomes of diplonemids. Nucleic Acids Res. 2020;48(5):2694–2708. doi: 10.1093/nar/gkz1215. PubMed DOI PMC

Warren JM, Sloan DB. Interchangeable parts: the evolutionarily dynamic tRNA population in plant mitochondria. Mitochondrion. 2020;52:144–156. doi: 10.1016/j.mito.2020.03.007. PubMed DOI

Salinas-Giegé T, Giegé R, Giegé P. tRNA biology in mitochondria. Int J Mol Sci. 2015;16(3):4518–4559. doi: 10.3390/ijms16034518. PubMed DOI PMC

Valach M, Benz C, Aguilar LC, Gahura O, Faktorová D, Zíková A, Oeffinger M, Burger G, Gray MW, Lukeš J. Miniature RNAs are embedded in an exceptionally protein-rich mitoribosome via an elaborate assembly pathway. Nucleic Acids Res. 2023;51(12):6443–60. PubMed PMC

Boxma B, de Graaf RM, van der Staay GW, van Alen TA, Ricard G, Gabaldón T, van Hoek AH, Moon-vander Staay SY, Koopman WJ, van Hellemond JJ, et al. An anaerobic mitochondrion that produces hydrogen. Nature. 2005;434(7029):74–79. doi: 10.1038/nature03343. PubMed DOI

de Graaf RM, Ricard G, van Alen TA, Duarte I, Dutilh BE, Burgtorf C, Kuiper JW, van der Staay GW, Tielens AG, Huynen MA, et al. The organellar genome and metabolic potential of the hydrogen-producing mitochondrion of Nyctotherus ovalis. Mol Biol Evol. 2011;28(8):2379–2391. doi: 10.1093/molbev/msr059. PubMed DOI PMC

Allen JF, Santabarbara S, Allen CA, Puthiyaveetil S. Discrete redox signaling pathways regulate photosynthetic light-harvesting and chloroplast gene transcription. PLoS ONE. 2011;6(10):e26372. doi: 10.1371/journal.pone.0026372. PubMed DOI PMC

Pearce SF, Rebelo-Guiomar P, D’Souza AR, Powell CA, Van Haute L, Minczuk M. Regulation of mammalian mitochondrial gene expression: recent advances. Trends Biochem Sci. 2017;42(8):625–639. doi: 10.1016/j.tibs.2017.02.003. PubMed DOI PMC

Jacob AS, Andersen LO, Bitar PP, Richards VP, Shah S, Stanhope MJ, Stensvold CR, Clark CG. Blastocystis mitochondrial genomes appear to show multiple independent gains and losses of start and stop codons. Genome Biol Evol. 2016;8(11):3340–3350. doi: 10.1093/gbe/evw255. PubMed DOI PMC

Brandvain Y, Wade MJ. The functional transfer of genes from the mitochondria to the nucleus: the effects of selection, mutation, population size and rate of self-fertilization. Genetics. 2009;182(4):1129–1139. doi: 10.1534/genetics.108.100024. PubMed DOI PMC

Formenti G, Rhie A, Balacco J, Haase B, Mountcastle J, Fedrigo O, Brown S, Capodiferro MR, Al-Ajli FO, Ambrosini R, et al. Complete vertebrate mitogenomes reveal widespread repeats and gene duplications. Genome Biol. 2021;22(1):120. doi: 10.1186/s13059-021-02336-9. PubMed DOI PMC

Birchler JA, Yang H. The multiple fates of gene duplications: deletion, hypofunctionalization, subfunctionalization, neofunctionalization, dosage balance constraints, and neutral variation. Plant Cell. 2022;34(7):2466–2474. doi: 10.1093/plcell/koac076. PubMed DOI PMC

Fallahi M, Crosthwait J, Calixte S, Bonen L. Fate of mitochondrially located S19 ribosomal protein genes after transfer of a functional copy to the nucleus in cereals. Mol Genet Genom. 2005;273(1):76–83. doi: 10.1007/s00438-004-1102-9. PubMed DOI

Atluri S, Rampersad SN, Bonen L. Retention of functional genes for S19 ribosomal protein in both the mitochondrion and nucleus for over 60 million years. Mol Genet Genom. 2015;290(6):2325–2333. doi: 10.1007/s00438-015-1087-6. PubMed DOI

van den Boogaart P, Samallo J, Agsteribbe E. Similar genes for a mitochondrial ATPase subunit in the nuclear and mitochondrial genomes of Neurospora crassa. Nature. 1982;298(5870):187–189. doi: 10.1038/298187a0. PubMed DOI

Nugent JM, Palmer JD. RNA-mediated transfer of the gene coxII from the mitochondrion to the nucleus during flowering plant evolution. Cell. 1991;66(3):473–481. doi: 10.1016/0092-8674(81)90011-8. PubMed DOI

Sandoval P, León G, Gómez I, Carmona R, Figueroa P, Holuigue L, Araya A, Jordana X. Transfer of RPS14 and RPL5 from the mitochondrion to the nucleus in grasses. Gene. 2004;324:139–147. doi: 10.1016/j.gene.2003.09.027. PubMed DOI

Choi C, Liu Z, Adams KL. Evolutionary transfers of mitochondrial genes to the nucleus in the Populus lineage and coexpression of nuclear and mitochondrial Sdh4 genes. New Phytol. 2006;172(3):429–439. doi: 10.1111/j.1469-8137.2006.01821.x. PubMed DOI

Allio R, Donega S, Galtier N, Nabholz B. Large variation in the ratio of mitochondrial to nuclear mutation rate across animals: implications for genetic diversity and the use of mitochondrial DNA as a molecular marker. Mol Biol Evol. 2017;34(11):2762–2772. doi: 10.1093/molbev/msx197. PubMed DOI

Baruffini E, Lodi T, Dallabona C, Foury F. A single nucleotide polymorphism in the DNA polymerase gamma gene of Saccharomyces cerevisiae laboratory strains is responsible for increased mitochondrial DNA mutability. Genetics. 2007;177(2):1227–1231. doi: 10.1534/genetics.107.079293. PubMed DOI PMC

Melde RH, Bao K, Sharp NP. Recent insights into the evolution of mutation rates in yeast. Curr Opin Genet Dev. 2022;76:101953. doi: 10.1016/j.gde.2022.101953. PubMed DOI PMC

Sharp NP, Sandell L, James CG, Otto SP. The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast. Proc Natl Acad Sci. 2018;115(22):E5046–E5055. doi: 10.1073/pnas.1801040115. PubMed DOI PMC

Lynch M, Koskella B, Schaack S. Mutation pressure and the evolution of organelle genomic architecture. Science. 2006;311(5768):1727–1730. doi: 10.1126/science.1118884. PubMed DOI

Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden TL. BLAST plus: architecture and applications. BMC Bioinformatics. 2009;10:421. PubMed PMC

Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013;30(4):772–780. doi: 10.1093/molbev/mst010. PubMed DOI PMC

Steinegger M, Meier M, Mirdita M, Vöhringer H, Haunsberger SJ, Söding J. HH-suite3 for fast remote homology detection and deep protein annotation. BMC Bioinformatics. 2019;20(1):473. doi: 10.1186/s12859-019-3019-7. PubMed DOI PMC

Rice P, Longden I, Bleasby A. EMBOSS: the European molecular biology open software suite. Trends Genet: TIG. 2000;16:276–277. doi: 10.1016/S0168-9525(00)02024-2. PubMed DOI

Lowe TM, Eddy SR. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 1997;25(5):955–964. doi: 10.1093/nar/25.5.955. PubMed DOI PMC

Laslett D, Canbäck B. ARAGORN, a program to detect tRNA genes and tmRNA genes in nucleotide sequences. Nucleic Acids Res. 2004;32:11–16. doi: 10.1093/nar/gkh152. PubMed DOI PMC

Fukasawa Y, Tsuji J, Fu S-C, Tomii K, Horton P, Imai K. MitoFates: improved prediction of mitochondrial targeting sequences and their cleavage sites *[S] Mol Cell Proteomics. 2015;14(4):1113–1126. doi: 10.1074/mcp.M114.043083. PubMed DOI PMC

Almagro Armenteros JJ, Salvatore M, Emanuelsson O, Winther O, von Heijne G, Elofsson A, Nielsen H. Detecting sequence signals in targeting peptides using deep learning. Life Sci Alliance. 2019;2(5):e201900429. PubMed PMC

Savojardo C, Martelli PL, Fariselli P, Casadio R. TPpred3 detects and discriminates mitochondrial and chloroplastic targeting peptides in eukaryotic proteins. Bioinformatics. 2015;31(20):3269–3275. doi: 10.1093/bioinformatics/btv367. PubMed DOI

Richter DJ, Berney C, Strassert JFH, Poh Y-P, Herman EK, Muñoz-Gómez SA, Wideman JG, Burki F, de Vargas C. EukProt: a database of genome-scale predicted proteins across the diversity of eukaryotes. Peer Commun J. 2022;2:e56.

Fu L, Niu B, Zhu Z, Wu S, Li W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics. 2012;28(23):3150–3152. doi: 10.1093/bioinformatics/bts565. PubMed DOI PMC

Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics. 2009;25(15):1972–1973. doi: 10.1093/bioinformatics/btp348. PubMed DOI PMC

Steenwyk JL, Buida TJ, III, Li Y, Shen X-X, Rokas A. ClipKIT: a multiple sequence alignment trimming software for accurate phylogenomic inference. PLoS Biol. 2020;18(12):e3001007. doi: 10.1371/journal.pbio.3001007. PubMed DOI PMC

Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD, von Haeseler A, Lanfear R. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol. 2020;37(5):1530–1534. doi: 10.1093/molbev/msaa015. PubMed DOI PMC

Reconstructing the last common ancestor of all eukaryotes