continued colonization of the human genome by mitochondrial dna继续殖民线粒体dna的人类基因组.pdfVIP

Open access, freely available online PLoS BIOLOGY Continued Colonization of the Human Genome by Mitochondrial DNA 1,2* 1 1 Miria Ricchetti , Fredj Tekaia , Bernard Dujon ´ ´ ´ ´ 1 Unite de Genetique Moleculaire 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 Unite de Genetique et Biochimie du Developpement (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 co