Continued Colonization of the Human Genome by Mitochondrial DNA

Ricchetti, Miria; Tekaia, Fredj; Dujon, Bernard

doi:10.1371/journal.pbio.0020273

Cited by 202 publications

(235 citation statements)

References 39 publications

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“…We estimated that this mtDNA insertion is a recent evolutionary event (30,000 YA) supporting the view that mtDNA integration into the nuclear genome is an ongoing process (Yu and Gabriel 1999;Adams et al 2000;Ricchetti et al 2004). Furthermore, our results demonstrate that the telomeres can be a port of entry for organellar DNA into the nuclear genome.…”

Section: Discussionsupporting

confidence: 84%

Natural Variation in a Subtelomeric Region of Arabidopsis: Implications for the Genomic Dynamics of a Chromosome End

2006

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We investigated genome dynamics at a chromosome end in the model plant Arabidopsis thaliana through a study of natural variation in 35 wild accessions. We focused on the single-copy subtelomeric region of chromosome 1 north (3.5 kb), which represents the relatively simple organization of subtelomeric regions in this species. PCR fragment-length variation across the subtelomeric region indicated that the 1.4-kb distal region showed elevated structural variation relative to the centromere-proximal region. Examination of nucleotide sequences from this 1.4-kb region revealed diverse DNA rearrangements, including an inversion, several deletions, and an insertion of a retrotransposon LTR. The structures at the deletion and inversion breakpoints are characteristic of simple deletion-associated nonhomologous endjoining (NHEJ) events. There was strong linkage disequilibrium between the distal subtelomeric region and the proximal telomere, which contains degenerate and variant telomeric repeats. Variation in the proximal telomere was characterized by the expansion and deletion of blocks of repeats. Our sample of accessions documented two independent chromosome-healing events associated with terminal deletions of the subtelomeric region as well as the capture of a scrambled mitochondrial DNA segment in the proximal telomeric array. This natural variation study highlights the variety of genomic events that drive the fluidity of chromosome termini.

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Section: Discussionsupporting

confidence: 84%

Natural Variation in a Subtelomeric Region of Arabidopsis: Implications for the Genomic Dynamics of a Chromosome End

2006

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“…Although indirect evidence of the same process occurring in some higher organisms has been published (17,38), the present study has been able to demonstrate directly that organelle DNA integrates at DSBs in multicellular eukaryotes. In previous experiments (39,40), in the absence of stress, no cytoplasmic organelle DNA insertions were observed at sites of nuclear DSBs.…”

Section: Discussionsupporting

confidence: 48%

Environmental stress increases the entry of cytoplasmic organellar DNA into the nucleus in plants

Wang

Lloyd

Timmis

2012

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria and chloroplasts (photosynthetic members of the plastid family of cytoplasmic organelles) in eukaryotic cells originated more than a billion years ago when an ancestor of the nucleated cell engulfed two different prokaryotes in separate sequential events. Extant cytoplasmic organellar genomes contain very few genes compared with their candidate free-living ancestors, as most have functionally relocated to the nucleus. The first step in functional relocation involves the integration of inactive DNA fragments into nuclear chromosomes, and this process continues at high frequency with attendant genetic, genomic, and evolutionary consequences. Using two different transplastomic tobacco lines, we show that DNA migration from chloroplasts to the nucleus is markedly increased by mild heat stress. In addition, we show that insertion of mitochondrial DNA fragments during the repair of induced double-strand breaks is increased by heat stress. The experiments demonstrate that the nuclear influx of organellar DNA is a potentially a source of mutation for nuclear genomes that is highly susceptible to temperature fluctuations that are well within the range experienced naturally.D NA in the highly energetic cytoplasmic organellar genetic compartments of eukaryotes is subjected to high levels of stress damage from the oxygen free radicals produced during respiration and photosynthesis. Nonetheless, for various reasons, the rate of accumulation of mutations is slower in plant cytoplasmic organelles than in the nucleus (1, 2). The vast majority of mitochondrial and plastid (chloroplast) genes have vacated their ancestral prokaryote genetic compartment in favor of the nucleus (2), with very few remaining within extant organelles. The first step in gene relocation for the organelle genomes is DNA escape, followed by insertion into nuclear chromosomes, a process shown to occur remarkably frequently under normal physiological conditions in tobacco (3, 4) and yeast (5), although an experimental screen in the unicellular alga Chlamydomonas reinhardtii did not detect any such transpositions (6). These experimental studies, together with bioinformatic and genomic analyses (7)(8)(9)(10)(11)(12)(13)(14), demonstrated that DNA transfer from cytoplasmic organelles is a frequent and continuous process in essentially all eukaryotes examined, although it may be very rare in organisms with very low organelle numbers (15). Although DNA transfer per se is very frequent in higher plants, genes that migrate are normally inactive in the nucleus because they lack the motifs required for nuclear expression. Nonetheless, on rare occasions nuclear integrants of organelle DNA (norgs) are activated by genomic rearrangements (16,17), that effectively duplicate the gene. Over evolutionary time, these frequent nonfunctional and rare functional DNA transfer processes have resulted in the net loss of redundant genes in the cytoplasmic organelles and have added to the genetic complexity of the nucleus.Environmental factors are known to modify mitoch...

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“…Although most such transfers involve small, apparently random fragments of organellar DNA that have no notable impact on the nuclear genome, entire genes can be transferred and expressed in their new environment (for example, see refs 39, 40). Instances in which NUMTs have altered existing genes by introducing new introns or truncating the gene through frameshifts have also been observed (for example, see refs [41][42][43].…”

Section: Why Do Nucleomorphs Persist?mentioning

confidence: 99%