Wednesday, 25 February 2015

Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations

Mingkun Li, Roland Schröder, Shengyu Ni et al.

Currently, there is little evidence to support the role of positive selection for mutations in mtDNA; indeed there is evidence that in proliferative tissue, it is negative selection which is the greater force. In this large-scale study, the authors explore the prevalence of different mutations from post-mortem tissues across 152 individuals. They find that particular heteroplasmies occur at particularly high frequencies, based on their nucleotide position, the tissue and the consensus allele. In agreement with other studies, the authors find that the number of heteroplasmies correlates with age. 

The functional explanation for tissue-related and allele-related selection remains unknown, but the authors suggest that it is possibly the metabolic requirements of each tissue which generates a selective pressure. As a case-study, the authors show that there is a strong positive selection for heteroplasmies in the liver which decrease mitochondrial function. Since many metabolic processes in the liver generate damaging byproducts, mutations which result in reduced function may be a means to avoid further damage, dubbed as 'survival of the slowest'.


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