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Mitochondrial DNA migration events in yeast and humans: integration by a common end-joining mechanism and alternative perspectives on nucleotide substitution patterns.

In contrast to extensive infiltration of plant nuclear genomes by mitochondrial and chloroplast DNA fragments, a computer assessment method could only detect seven mitochondrial DNA integration events in Saccharomyces cerevisiae chromosomes and five examples of DNA migration into mammalian nuclear genes. No evidence could be detected for mitochondrial DNA insertion into chromosome III of Caenorhabditis elegans or in nuclear DNA sequences of Drosophila sp. or Plasmodium falciparum. Thus, the quantity of organellar DNA in the nucleus appears to vary amongst organisms and is lower in Saccharomyces cerevisiae than suggested by experimental plasmid systems. As in plants, migratory mitochondrial DNA fragments in yeast and mammals are found in intergenic regions and introns. Although many of these insertions are located near retroelements, mitochondrial DNA incorporation appears to be independent of retroelement insertion. Comparison of the mitochondrial DNA fragments with mitochondrial transcription maps suggest that two fragments may have transposed through DNA-based and one through RNA-based mechanisms. Analyses of the integration sites indicate that organellar DNA sequences are incorporated by an end-joining mechanism common to yeast, mammals, and plants. The transferred sequences also provide a novel perspective on rates and patterns of nucleotide substitution. Analysis of the D-loop region including a nuclear copy of mitochondrial DNA supports a progressive reduction in D-loop length within both monkey and great apes mitochondrial lineages. Relative distance tests polarized with nuclear copies of the mitochondrial 12S/16S rRNA region suggest that a constant number of transversions has accumulated within the great ape clade, but the number of transitions in orangutan is elevated with respect to members of the human/chimp/gorilla clade. In addition to DNA migration events, 29 nuclear/mitochondrial genes were identified in GenBank that appear to result from inadvertent ligation of nuclear and mitochondrial mRNA transcripts during the cloning process.