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Biologists map rare case of fitness-reducing interaction in nuclear, mitochondrial DNA
Date:2/5/2013

BLOOMINGTON, Ind. -- A team of biologists from Indiana University and Brown University believes it has discovered the mechanism by which interacting mutations in mitochondrial and nuclear DNA produce an incompatible genotype that reduces reproductive fitness and delays development in fruit flies.

The new research, led by IU biologists Kristi Montooth and Colin Meiklejohn and including former IU undergraduate researcher Mo Siddiq, describes the cause and consequences of an interaction between the two genomes that co-exist within eukaryotic cells. Animal mitochondrial DNA, or mtDNA, is a small but important genome that encodes a handful of proteins that are essential to oxidative phosphorylation, the pathway that produces the adenosine triphosphate molecule that fuels cellular metabolism.

With this new characterization of a disruptive interaction between mtDNA and nuclear DNA mutations, the scientists provide one of the few mapped cases of a fitness-reducing mitochondrial-nuclear incompatibility.

The genetic interaction that IU biologists mapped, in collaboration with Brown University biologist David Rand, is between mutations that are present in natural populations, rather than being induced in the lab. This has important consequences for understanding genetically complex human diseases.

Many human diseases, such as neuromuscular and neurodegenerative disorders, are associated with mutations in mitochondrial transfer RNAs, or tRNAs, but a single mutation can be highly variable in the degree to which it leads to disease.

Montooth and her colleagues' findings suggest that the combined mitochondrial-nuclear genotype for tRNAs and their tRNA synthetases may, in fact, be a better predictor of disease.

"Interactions between mitochondrial and nuclear DNA for fitness have been documented in many organisms, but rarely has the genetic or mechanistic basis of these interactions been elucidated," said Montooth,
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Contact: Steve Chaplin
stjchap@iu.edu
812-856-1896
Indiana University
Source:Eurekalert  

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