Selections that isolate recombinant mitochondrial genomes in animals.
Selections that isolate recombinant mitochondrial genomes in animals.
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DOI：
10.7554/elife.07247
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发表时间：
2015-08-03
期刊：
影响因子：
7.7
通讯作者：
O'Farrell PH
中科院分区：
文献类型：
--
作者：
Ma H;O'Farrell PH
Homologous recombination is widespread and catalyzes evolution. Nonetheless, its existence in animal mitochondrial DNA is questioned. We designed selections for recombination between co-resident mitochondrial genomes in various heteroplasmic Drosophila lines. In four experimental settings, recombinant genomes became the sole or dominant genome in the progeny. Thus, selection uncovers occurrence of homologous recombination in Drosophila mtDNA and documents its functional benefit. Double-strand breaks enhanced recombination in the germline and revealed somatic recombination. When the recombination partner was a diverged Drosophila melanogaster genome or a genome from a different species such as Drosophila yakuba, sequencing revealed long continuous stretches of exchange. In addition, the distribution of sequence polymorphisms in recombinants allowed us to map a selected trait to a particular region in the Drosophila mitochondrial genome. Thus, recombination can be harnessed to dissect function and evolution of mitochondrial genome. DOI: http://dx.doi.org/10.7554/eLife.07247.001 Animals store the main part of their DNA—including all of the genes that are required to build and maintain an individual—inside their cells in a structure called the nucleus. Most of the information stored in the DNA is stored in duplicate, with one copy inherited from the individual's mother via the egg, and the other from the father via the sperm. This duplicate storage allows a very important damage repair process to occur, where undamaged sequences in one copy can be used to repair damage in the other. This process of homologous repair uses mechanisms that are also used in another important genetic process. When sperm and egg cells are formed, the parental DNA goes through a process called homologous recombination, in which DNA molecules are cut and reassembled into new arrangements. This recombination process ‘shuffles’ genetic combinations, making every individual unique—a process of great evolutionary importance that allows natural selection to act on distinct traits. The structures inside cells that generate energy—called mitochondria—also contain DNA, which is inherited only from mothers. Little is known about whether recombination is possible in the mitochondrial DNA of animals. Ma and O'Farrell used genetics techniques to investigate recombination in the mitochondria of fruit flies. One experiment tracked how a mutation that makes flies less healthy at high temperatures spread as flies were bred for several generations. When the mutation was associated with a mitochondrial genome that had a strong drive towards replication, the mutation became more widespread over time, and in most cases, this eventually resulted in the mutation killing the flies. In rare cases, however, a few flies survived, giving rise to a healthy population. Molecular analyses revealed that, in these survivors, the defective genome had recombined with the other mitochondrial DNA to produce a new genome that lacked the mutation but retained the high replicative drive. This new recombinant genome worked normally and was able to resist the spread of the defective genomes. In addition, by artificially cutting mitochondrial DNA, Ma and O'Farrell show that such ‘double-strand breaks’ lead to recombination, signaling a role for homologous repair in the repair of damaged, in this case broken, DNA. Recombination is also possible between the mitochondrial DNA of two different fruit fly species, and this recombination process can assemble long stretches of DNA. Now that the recombination of animal mitochondrial DNA is known to be possible, future work will be required to understand how it works and how it affects evolution. DOI: http://dx.doi.org/10.7554/eLife.07247.002
