Evolutionary genetics

Selective inheritance of mitochondrial DNA

Two studies in Drosophila melanogaster provide insights into the mechanisms that prevent the transmission of harmful mutations in mitochondrial DNA (mtDNA). By disrupting mitochondrial function using RNA interference, Hill et al. show that mtDNA replication in the germ line depends on organelle fitness. Using heteroplasmic flies, which contain both wild-type and mutant mitochondrial genomes, they then found that the transmission of the deleterious genome — containing a temperature-sensitive lethal mtDNA allele — was gradually purged over several generations at the restrictive temperature. This finding indicates that selection against the mutant mtDNA occurs to ensure the inheritance of healthy mitochondria to successive generations. The authors propose that mitochondria with a high proportion of wild-type mtDNA replicate faster than those containing more mutations, which leads to “a decrease in the proportion of mutant mtDNA through oogenesis,” as the authors state. In the second study, Ma et al. show that purifying selection results from competition between mitochondrial genomes within an organism without any effect on organismal survival or fertility. In addition, the researchers show that selection can stabilize the transmission over multiple generations of harmful variants that complement each other. For as long as they are selected at stable ratios, the complementing mutations are not deleterious.

References

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    Hill, J. H., Chen, Z. & Xu. H. Selective propagation of functional mitochondrial DNA during oogenesis restricts the transmission of a deleterious mitochondrial variant.Nature Genet. 46, 389–392 (2014)

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    Ma, H., Xu, H. & O'Farrell, P. H. Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster.Nature Genet. 46, 393–397 (2014)

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Koch, L. Selective inheritance of mitochondrial DNA. Nat Rev Genet 15, 288 (2014). https://doi.org/10.1038/nrg3725

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