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posted 30. September 2004 11:54
PLoS Biology. Volume 2 | Issue 9 | September 2004
Continued Colonization of the Human Genome by Mitochondrial DNA
Miria Ricchetti1, Fredj Tekaia1, Bernard Dujon
Unité de Génétique Moléculaire des Levures (UFR 927 Univ. P. et M. Curie and URA 2171 CNRS), Department of Structure and Dynamics of Genomes, Institut Pasteur, Paris, France, 2 Unité de Génétique et Biochimie du Développement (URA 1960 CNRS), Department of Immunology, Institut Pasteur, Paris, France
Integration of mitochondrial DNA fragments into nuclear chromosomes (giving rise to nuclear DNA sequences of mitochondrial origin, or NUMTs) is an ongoing process that shapes nuclear genomes. In yeast this process depends on double-strand-break repair. Since NUMTs lack amplification and specific integration mechanisms, they represent the prototype of exogenous insertions in the nucleus. From sequence analysis of the genome of Homo sapiens, followed by sampling humans from different ethnic backgrounds, and chimpanzees, we have identified 27 NUMTs that are specific to humans and must have colonized human chromosomes in the last 4–6 million years. Thus, we measured the fixation rate of NUMTs in the human genome. Six such NUMTs show insertion polymorphism and provide a useful set of DNA markers for human population genetics. We also found that during recent human evolution, Chromosomes 18 and Y have been more susceptible to colonization by NUMTs. Surprisingly, 23 out of 27 human-specific NUMTs are inserted in known or predicted genes, mainly in introns. Some individuals carry a NUMT insertion in a tumor-suppressor gene and in a putative angiogenesis inhibitor. Therefore in humans, but not in yeast, NUMT integrations preferentially target coding or regulatory sequences. This is indeed the case for novel insertions associated with human diseases and those driven by environmental insults. We thus propose a mutagenic phenomenon that may be responsible for a variety of genetic diseases in humans and suggest that genetic or environmental factors that increase the frequency of chromosome breaks provide the impetus for the continued colonization of the human genome by mitochondrial DNA.
Received March 4, 2004; Accepted June 16, 2004; Published September 7, 2004
Copyright: © 2004 Ricchetti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abbreviations: DSB, double-strand break; mt, mitochondrial; Myr, million years; NHEJ, non-homologous end-joining; NUMT, nuclear DNA sequence of mitochondrial origin
Academic Editor: Jonathan A. Eisen, Institute for Genomic Research
*To whom correspondence should be addressed. E-mail: firstname.lastname@example.org
Citation: Ricchetti M, Tekaia F, Dujon B (2004) Continued Colonization of the Human Genome by Mitochondrial DNA. PLoS Biol 2(9): e273.
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