Author:
Holt Alan G,Davies Adrian M
Abstract
AbstractIn this paper we propose that high copy number of the mitochondrial genome in neurons is a functional adaptation. We simulated the proliferation of deletion mutants of the human mitochondrial genome in a virtual mitochondrion and recorded the cell loss rates due to deletions overwhelming the wild-type.Our results showed that cell loss increased with mtDNA copy number. Given that neuron loss equates to cognitive dysfunction, it would seem counter-intuitive that there would be a selective pressure for high copy number over low. However, for a low copy number, the onset of cognitive decline, while mild, started early in life. Whereas, for high copy number, it did not start until middle age but progressed rapidly. There could have been an advantage to high copy number in the brain if it delayed the onset of cognitive decline until after reproductive age. The prevalence of dementia in our aged population is a consequence of this functional adaptation.
Publisher
Cold Spring Harbor Laboratory
Reference38 articles.
1. Cell number changes in Alzheimer's disease relate to dementia, not to plaques and tangles
2. Early neurone loss in alzheimer’s disease: cortical or subcortical?;Acta neuropathologica communications,2015
3. Miriam Baron . Copy number variations of the mitochondrial DNA as potential cause of mitochondrial diseases. PhD thesis, Universitäts-und Landesbibliothek Bonn, 2010.
4. Detrimental deletions: mitochondria, aging and Parkinson's disease
5. Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease