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A battle of dominance: should mitochondrial DNA be selfless or selfish?

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Mitochondrial DNA (mtDNA) is a maternally-inherited genome that encodes important subunits of the respiratory chain. Given that there are multiple copies of mtDNA within each cell, pathogenic mutations often arise among thousands of wild-type genomes. Selectivity in transmission of functional versus pathogenic genomes in somatic cells impacts expression of disease phenotype. While selective transmission in germline governs the heritance of mtDNA mutations into progeny, and thus its evolution. However, what influences the competition of co-existing mitochondrial genomes is not yet clear.

Recently, we have developed Drosophila as a powerful model for mtDNA studies. This helped to resolve two types of selection that influence the competition between mitochondrial genomes: 1) a purifying selection where the genome providing more function always takes over. This selection plays an essential role in keeping the functional integrity of mtDNA during evolution; 2) a selfish selection where a bully genome gain over a wimpy genome if it replicates or transmits better (i.e. independent of function). This selection allows different mutations that enhance replication to accumulate in different female lineages, thus enhancing mtDNA diversity. For an individual, when the gains in one selection are balanced by losses in the other, both genomes are maintained in a stable ratio for many generations. We have established such a line in Drosophila that stably carries two mitochondrial genomes, one that benefits from a selection for function and one with a replicative advantage. Currently, we are performing a deficiency genetic screen to identify nuclear regions/genes whose genetic dose influence the stable balance of these mitochondrial genomes, in order to identify nuclear genes impacting the selective transmission of mtDNA.

This talk is part of the Cambridge Fly Meetings series.

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