Friday, 1 May 2015

Selection against Heteroplasmy Explains the Evolution of Uniparental Inheritance of Mitochondria

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005112

Joshua R. Christie, Timothy M. Schaerf and Madeleine Beekman

Mitochondria are maternally inherited, but the selective advantage of this is debated. Nuclear DNA obeys Mendelian inheritance, which increases genetic variance in offspring, and allows the selection of advantageous genotypes. Why is this actively avoided in mitochondrial DNA (mtDNA)?

This study hinges on the following observation: the mixture (heteroplasmy, h) of two normal mtDNA haplotypes in an individual can cause physiological and behavioural abnormalities. Thus an individual is most fit when it is homoplasmic (h = 0 or h = 1) in its mtDNA. The authors explore this mathematically by generating a model of single-celled eukaryotes, obeying biparental inheritance, undergoing a cell cycle of four stages:  random mating of cells; mutation of mtDNA; selection based on a fitness function of h; and finally meiosis. The fitness functions considered by the authors all had a minimum at h = 1/2.

The authors initialise their model of biparental-inheritance, and allow it to equilibriate. They then introduce a small population of cells (1%) which instead have a nuclear allele which encodes mitochondrial uniparental inheritance. The authors find that, despite this small initial population of uniparental cells, they eventually come to dominate, such that the system purely obeys uniparental inheritance. Thus, selection against heteroplasmy is sufficient to explain a fitness advantage of uniparental inheritance. 



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