Global InformationNuclear mitochondrial DNA segment information
 | This article's lead section may be too long. (January 2023) |
Nuclear mitochondrial DNA (NUMT) segments or genetic loci describe a transposition of any type of cytoplasmic mitochondrial DNA into the nuclear genome of eukaryotic organisms.[1][2][3]
More NUMT sequences of different sizes and lengths in the diverse number of eukaryotes have been detected as whole genome sequencing of different organisms accumulates.[4] They have often been unintentionally discovered by researchers who were looking for mitochondrial DNA (mtDNA).[5] NUMTs have been reported in all studied eukaryotes, and nearly all mitochondrial genome regions can be integrated into the nuclear genome.[6][7] However, NUMTs differ in number and size across different species.[6][8][9] Such differences may be accounted for by interspecific variation in such factors as germline stability and mitochondria number.[10] After the release of the mtDNA into the cytoplasm, due to the mitochondrial alteration and morphological changes, it is transferred into the nucleus[1][5] and inserted by double-stranded break repair processes into the nuclear DNA (nDNA).[1] A correlation has been found between the fraction of noncoding DNA and NUMT abundance in the genome,[10][11][12] and NUMTs are observed to have non-random distribution and a higher likelihood of being inserted in certain genomic regions.[12] Depending on the location of the insertion, NUMTs might disrupt gene function.[1] In addition, de novo integration of NUMT pseudogenes into the nuclear genome can have adverse effects.[13][14][15][16]
In the domestic cat, mitochondrial gene number and content were amplified 38 to 76 times in the cat's nuclear genome besides being transposed from the cytoplasm.[17] Cat NUMT sequences did not appear to be functional due to the discovery of multiple mutations, differences in mitochondrial and nuclear genetic codes, and the apparent insertion within typically inert centromere regions. The presence of NUMT fragments in the genome is not problematic in all species; for instance, it is shown that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae.[15] Although the extended translocation of mtDNA fragments and their co-amplification with free mitochondrial DNA has been problematic in the diagnosis of mitochondrial disorders, in the study of population genetics and phylogenetic analyses,[1] scientists have used NUMTs as genetic markers to determine the relative rate of nuclear and mitochondrial mutation and recreating the evolutionary tree.[16]
In 2022, scientists reported the discovery of ongoing transfer of mitochondrial DNA into DNA in the cell nucleus. Previously, NUMTs were thought to have arisen before the existence of humans. 66,000 whole-genome sequences indicate this occurs as frequently as approximately once every 4,000 human births.[18][19]
- ^ a b c d e Gaziev, A. I.; Shaikhaev, G. O (2010). "Nuclear Mitochondrial Pseudogenes". Molecular Biology. 44 (3): 358–368. doi:10.1134/s0026893310030027. PMID 20608164. S2CID 22819449.
- ^ Lopez, J.V., Yuhki, N., Modi, W., Masuda, R. and O'Brien, S.J. (1994). "Numt, a recent transfer and tandem amplification of mitochondrial DNA in the nuclear genome of the domestic cat". J Mol Evol. 39 (2): 174–190. Bibcode:1994JMolE..39..174L. doi:10.1007/BF00163806. PMID 7932781. S2CID 22165470.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Lopez, J.V.; Stephens, J.C; O'Brien, S.J. (1997). "The long and short of nuclear mitochondrial lineages". Trends Ecol. Evol. 12 (3): 114. doi:10.1016/s0169-5347(97)84925-7. PMID 21238001.
- ^ Nomiyama, Hisayuki; et al. (1985). "Molecular Structures of Mitochondrial-DNA-Like Sequences in Human Nuclear DNA". Nucleic Acids Research. 13 (5): 1649–658. doi:10.1093/nar/13.5.1649. PMC 341102. PMID 2987834.
- ^ a b Hazkani-Covo, Einat; et al. (2010). "Molecular Poltergeists: Mitochondrial DNA Copies (NUMT) in Sequenced Nuclear Genomes". PLOS Genetics. 6 (2): e1000834. doi:10.1371/journal.pgen.1000834. PMC 2820518. PMID 20168995.
- ^ a b Mishmar, D., Ruiz-Pesini, E., Brandon, M. and Wallace, D.C. (2004). "Mitochondrial DNA-like sequences in the nucleus (NUMTs): Insights into our African origins and the mechanism of foreign DNA integration". Hum Mutat. 23 (2): 125–133. doi:10.1002/humu.10304. PMID 14722916. S2CID 25109836.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Qu, H., Ma, F. and Li, Q. (2008). "Comparative analysis of mitochondrial fragments transferred to the nucleus in vertebrate". J Genet Genomics. 35 (8): 485–490. doi:10.1016/S1673-8527(08)60066-1. PMID 18721785.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Sacerdot, C., Casaregola, S., Lafontaine, I., Tekaia, F., Dujon, B. and Ozier-Kalogeropoulos, O. (2008). "Promiscuous DNA in the nuclear genomes of hemiascomycetous yeasts". FEMS Yeast Res. 8 (6): 846–857. doi:10.1111/j.1567-1364.2008.00409.x. PMID 18673395.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Schizas, N.V. (2012). "Misconceptions regarding nuclear mitochondrial pseudogenes (Numts) may obscure detection of mitochondrial evolutionary novelties". Aquat Biol. 17: 91–96. doi:10.3354/ab00478.
- ^ a b Richly, E. (2004). "NUMTs in Sequenced Eukaryotic Genomes". Molecular Biology and Evolution. 21 (6): 1081–084. doi:10.1093/molbev/msh110. hdl:11858/00-001M-0000-0012-3BE0-F. PMID 15014143.
- ^ Rogers, Hubert H; Griffiths-Jones, Sam (2012). "Mitochondrial pseudogenes in the nuclear genomes of Drosophila". PLOS ONE. 7 (3): e32593. Bibcode:2012PLoSO...732593R. doi:10.1371/journal.pone.0032593. PMC 3296715. PMID 22412894.
- ^ a b Tsuji, J.; et al. (2012). "Mammalian NUMT Insertion Is Non-random". Nucleic Acids Research. 40 (18): 9073–088. doi:10.1093/nar/gks424. PMC 3467031. PMID 22761406.
- ^ Dayama, G; et al. (2014). "The Genomic Landscape of Polymorphic Human Nuclear Mitochondrial Insertions". Nucleic Acids Res. 42 (20): 12640–12649. doi:10.1093/nar/gku1038. PMC 4227756. PMID 25348406.
- ^ Hazkani-Covo, E; Graur, D (2006). "A Comparative Analysis of NUMT Evolution in Human and Chimpanzee". Molecular Biology and Evolution. 24 (1): 13–18. doi:10.1093/molbev/msl149. PMID 17056643.
- ^ a b Chatre, Lauren; Ricchetti, Miria (2011). "Nuclear Mitochondrial DNA Activates Replication in Saccharomyces Cerevisiae". PLOS ONE. 6 (3): e17235. Bibcode:2011PLoSO...617235C. doi:10.1371/journal.pone.0017235. PMC 3050842. PMID 21408151.
- ^ a b Bensasson, D (2001). "Mitochondrial Pseudogenes: Evolution's Misplaced Witnesses". Trends in Ecology & Evolution. 16 (6): 314–321. doi:10.1016/s0169-5347(01)02151-6. PMID 11369110.
- ^ Lopez, Jose V; et al. (1996). "Complete Nucleotide Sequences of the Domestic Cat (Felis Catus) Mitochondrial Genome and a Transposed MtDNA Tandem Repeat (Numt) in the Nuclear Genome". Genomics. 33 (2): 229–46. doi:10.1006/geno.1996.0188. PMID 8660972.
- ^ "Mitochondrial DNA Is Working Its Way Into the Human Genome". Genomics Research from Technology Networks. Retrieved 17 November 2022.
- ^ Wei, Wei; Schon, Katherine R.; Elgar, Greg; Orioli, Andrea; Tanguy, Melanie; Giess, Adam; Tischkowitz, Marc; Caulfield, Mark J.; Chinnery, Patrick F. (November 2022). "Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes". Nature. 611 (7934): 105–114. Bibcode:2022Natur.611..105W. doi:10.1038/s41586-022-05288-7. ISSN 1476-4687. PMC 9630118. PMID 36198798.
- University press release: "A new route to evolution: How DNA from our mitochondria works its way into our genomes". University of Cambridge via phys.org. Retrieved 17 November 2022.