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Rates of DNA Duplication and Mitochondrial DNA Insertion in the Human Genome

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Abstract

The hundreds of mitochondrial pseudogenes in the human nuclear genome sequence (numts) constitute an excellent system for studying and dating DNA duplications and insertions. These pseudogenes are associated with many complete mitochondrial genome sequences and through those with a good fossil record. By comparing individual numts with primate and other mammalian mitochondrial genome sequences, we estimate that these numts arose continuously over the last 58 million years. Our pairwise comparisons between numts suggest that most human numts arose from different mitochondrial insertion events and not by DNA duplication within the nuclear genome. The nuclear genome appears to accumulate mtDNA insertions at a rate high enough to predict within-population polymorphism for the presence/absence of many recent mtDNA insertions. Pairwise analysis of numts and their flanking DNA produces an estimate for the DNA duplication rate in humans of 2.2 × 10−9 per numt per year. Thus, a nucleotide site is about as likely to be involved in a duplication event as it is to change by point substitution. This estimate of the rate of DNA duplication of noncoding DNA is based on sequences that are not in duplication hotspots, and is close to the rate reported for functional genes in other species.

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References

  1. JA Bailey Z Gu RA Clark K Reinert RV Samonte S Schwatz MD Adams EW Myers PW Li EE Eichler (2002a) ArticleTitleRecent segmental duplications in the human genome. Science 297 1003–1007

    Google Scholar 

  2. JA Bailey AM Yavor L Viggiano D Misceo JE Horvath N Archidiacono S Shchwartz M Rocchi EE Eichler (2002b) ArticleTitleHuman-specific duplication and mosaic transcripts: The recent paralogous structure of chromosome 22. Am J Hum Gene 70 83–100

    Google Scholar 

  3. D Bensasson D-X Zhang GM Hewitt (2000) ArticleTitleFrequent assimilation of mitochondrial DNA by grasshopper nuclear genomes. Mol Biol Evol 17 406–415 Occurrence Handle10723741

    PubMed  Google Scholar 

  4. D Bensasson D-X Zhang DL Hartl GM Hewitt (2001) ArticleTitleMitochondrial pseudogenes: Evolution’s misplaced witnesses. Trends Ecol Evol 16 314–321 Occurrence Handle11369110

    PubMed  Google Scholar 

  5. WM Brown EM Prager A Wang AC Wilson (1982) ArticleTitleMitochondrial DNA sequences of primates: Tempo and mode of evolution. J Mol Evol 18 225–239 Occurrence Handle1:CAS:528:DyaL38XitFGhs7s%3D Occurrence Handle6284948

    CAS  PubMed  Google Scholar 

  6. M Fukuda S Wakasugi T Tsuzuki H Nomiyama K Shimada T Miyata (1985) ArticleTitleMitochondrial DNA-like sequences in the human nuclear genome. J Mol Biol 186 257–266 Occurrence Handle3003363

    PubMed  Google Scholar 

  7. G Gellissen G Michaelis (1987) ArticleTitleGene transfer: Mitochondria to nucleus. Ann NY Acad Sci 503 391–401 Occurrence Handle3304081

    PubMed  Google Scholar 

  8. M Goodman CA Porter J Czelusniak SL Page H Schneider J Shoshani G Gunnell CP Groves (1998) ArticleTitleToward a phylogenetic classification of primates based on DNA evidence complemented by fossil evidence. Mol Phylogenet Evol 9 585–598 Occurrence Handle1:STN:280:DyaK1czjsVGrsQ%3D%3D Occurrence Handle9668008

    CAS  PubMed  Google Scholar 

  9. D Graur Y Shuali W-H Li (1989) ArticleTitleDeletions in processed pseudogenes accumulate faster in rodents than in humans. J Mol Evol 28 279–285 Occurrence Handle1:CAS:528:DyaL1MXitVKqsbc%3D Occurrence Handle2499684

    CAS  PubMed  Google Scholar 

  10. Z Gu A Cavalcanti F-C Chen B P W-H Li (2002) ArticleTitleExtent of gene duplication in the genomes of Drosophila, nematode, and yeast. Mol Biol Evol 19 256–262 Occurrence Handle11861885

    PubMed  Google Scholar 

  11. TA Hall (1999) ArticleTitleBioEdit: A user-friendly biological sequence alignment editor and analysis (program for windows 95/98/NT). Nucleic Acids Symp Ser 41 95–98 Occurrence Handle1:CAS:528:DC%2BD3cXhtVyjs7Y%3D

    CAS  Google Scholar 

  12. M Hasegawa H Kishino T Yano (1985) ArticleTitleDating of the human–ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol 22 160–174 Occurrence Handle1:CAS:528:DyaL2MXmtFSns7g%3D Occurrence Handle3934395

    CAS  PubMed  Google Scholar 

  13. E Hazkani-Covo R Sorek D Graur (2003) ArticleTitleEvolutionary dynamics of large numts in the human genome: Rarity of independent insertions and abundance of postinsertion duplications. J Mol Evol 56 169–174 Occurrence Handle10.1007/s00239-002-2390-5 Occurrence Handle12574863

    Article  PubMed  Google Scholar 

  14. G Hu WG Thilly (1994) ArticleTitleEvolutionary trail of the mitchondrial genome as based on human 16S rDNA pseudogenes. Gene 147 197–204 Occurrence Handle10.1016/0378-1119(94)90065-5 Occurrence Handle7926799

    Article  PubMed  Google Scholar 

  15. InstitutionalAuthorNameInternational Human Genome Sequencing Consortium (2001) ArticleTitleInitial sequencing and analysis of the human genome. Nature 409 860–921 Occurrence Handle1:CAS:528:DC%2BD3MXhsFCjtLc%3D Occurrence Handle11237011

    CAS  PubMed  Google Scholar 

  16. W-H Li (1997) Molecular evolution. Sinauer Associates Sunderland, MA

    Google Scholar 

  17. M Long K Thornton (2001) ArticleTitleGene duplication and evolution. Science 293 1551a Occurrence Handle10.1126/science.293.5535.1551a

    Article  Google Scholar 

  18. M Lynch JS Conery (2000) ArticleTitleThe evolutionary fate and consequences of duplicate genes. Science 290 1151–1155 Occurrence Handle10.1126/science.290.5494.1151 Occurrence Handle1:CAS:528:DC%2BD3cXotVChsb8%3D Occurrence Handle11073452

    Article  CAS  PubMed  Google Scholar 

  19. M Lynch JS Conery (2001) ArticleTitleGene duplication and evolution. Science 293 1551a Occurrence Handle10.1126/science.293.5535.1551a

    Article  Google Scholar 

  20. T Mourier AJ Hansen E Willerslev P Arctander (2001) ArticleTitleThe human genome project reveals a continuous transfer of large mitochondrial fragments to the nucleus. Mol Biol Evol 18 1833–1837

    Google Scholar 

  21. NI Mundy A Pissinatti DS Woodruff (2000) ArticleTitleMultiple nuclear insertions of mitochondrial cytochrome b sequences in callitrichine primates. Mol Biol Evol 17 1075–1080 Occurrence Handle10889220

    PubMed  Google Scholar 

  22. AY Ogurtsov MA Roytberg SA Shabalina AS Kondrashov (2002) ArticleTitleOWEN: Aligning long colinear regions of genomes. Bioinformatics 18 1703–1704 Occurrence Handle10.1093/bioinformatics/18.12.1703 Occurrence Handle12490463

    Article  PubMed  Google Scholar 

  23. R Ophir D Graur (1997) ArticleTitlePatterns and rates of indel evolution in processed pseudogenes from humans and murids. Gene 205 191–202 Occurrence Handle1:CAS:528:DyaK1cXmtlSqsQ%3D%3D Occurrence Handle9461394

    CAS  PubMed  Google Scholar 

  24. NT Perna TD Kocher (1996) ArticleTitleMitochondrial DNA: Molecular fossils in the nucleus. Curr Biol 6 128–129 Occurrence Handle8673455

    PubMed  Google Scholar 

  25. M Przeworski RR Hudson A Di Rienzo (2000) ArticleTitleAdjusting the focus on human variation. Trends Genet 16 296–302 Occurrence Handle1:CAS:528:DC%2BD3cXktlCnurY%3D Occurrence Handle10858659

    CAS  PubMed  Google Scholar 

  26. RV Samonte EE Eichler (2002) ArticleTitleSegmental duplications and the evolution of the primate genome. Nature Rev Genet 3 65–72 Occurrence Handle10.1038/nrg705

    Article  Google Scholar 

  27. J Schmitz M Ohme H Zischler (2001) ArticleTitleSINE insertions in cladistic analyses and the phylogenetic affiliations of Tarsius bancanus to other primates. Genetics 157 777–784 Occurrence Handle11156996

    PubMed  Google Scholar 

  28. J Schmitz M Ohme H Zischler (2002) ArticleTitleThe complete mitochondrial sequence of Tarsius bancanus: Evidence for an extensive nucleotide compositional plasticity of primate mitochondrial DNA. Mol Biol Evol 19 544–553 Occurrence Handle11919296

    PubMed  Google Scholar 

  29. DL Swofford (2002) PAUP*: Phylogenetic analysis using parsimony (* and other methods). Sinauer Associates Sunderland, MA

    Google Scholar 

  30. R Thomas H Zischler S Paabo M Stoneking (1996) ArticleTitleNovel mitochondrial DNA insertion polymorphism and its usefulness for human population studies. Hum Biol 68 847–854 Occurrence Handle1:STN:280:ByiC3svgsl0%3D Occurrence Handle8979460

    CAS  PubMed  Google Scholar 

  31. Y Tourmen O Baris P Dessen C Jacques Y Malthiéry P Reynier (2002) ArticleTitleStructure and chromosomal distribution of human mitochondrial pseudogenes. Genomics 80 71–77 Occurrence Handle10.1006/geno.2002.6798 Occurrence Handle1:CAS:528:DC%2BD38XkslSjtrw%3D Occurrence Handle12079285

    Article  CAS  PubMed  Google Scholar 

  32. GA Watterson (1975) ArticleTitleOn the number of segregating sites in genetical models without recombination. Theor Popul Biol 7 256–276 Occurrence Handle1:STN:280:CSqC1MbgvF0%3D Occurrence Handle1145509

    CAS  PubMed  Google Scholar 

  33. M Woischnik CT Moraes (2002) ArticleTitlePattern of organization of human mitochondrial pseudogenes in the nuclear genome. Genome Res 12 885–893 Occurrence Handle1:CAS:528:DC%2BD38Xks12hsro%3D Occurrence Handle12045142

    CAS  PubMed  Google Scholar 

  34. Z Yang (1997) ArticleTitlePAML: A program package for phylogenetic analysis by maximum likelihood. CABIOS 13 Occurrence Handle1:CAS:528:DyaK2sXntlGntrY%3D Occurrence Handle9367125

    CAS  PubMed  Google Scholar 

  35. JD Yuan JX Shi GX Meng LG An GX Hu (1999) ArticleTitleNuclear pseudogenes of mitochondrial DNA as a variable part of the human genome. Cell Res 9 281–290 Occurrence Handle1:STN:280:DC%2BD3c%2Fpt1Cmuw%3D%3D Occurrence Handle10628837

    CAS  PubMed  Google Scholar 

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Acknowledgements

Many thanks for helpful discussion, advice, and comments on the manuscript go to Aviv Bergman, Casey M. Bergman, Krista K. Ingram, and Dennis P. Wall, and to Jeffrey L. Boore for support in the later stages of this work. The comments of two anonymous reviewers substantially improved the manuscript. This work was partly funded by the Center for Computational Genetics and Biological Modeling.

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  1. School of Biological Sciences, Stanford University, 371 Serra Mall, Stanford, CA 94305, USA

    Douda Bensasson, Marcus W. Feldman & Dmitri A. Petrov

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  1. Douda Bensasson
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  2. Marcus W. Feldman
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  3. Dmitri A. Petrov
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Correspondence to Douda Bensasson.

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Bensasson, D., Feldman, M.W. & Petrov, D.A. Rates of DNA Duplication and Mitochondrial DNA Insertion in the Human Genome . J Mol Evol 57, 343–354 (2003). https://doi.org/10.1007/s00239-003-2485-7

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