Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric RestrictionReport as inadecuate




Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric Restriction - Download this document for free, or read online. Document in PDF available to download.

Background

Metabolism of energy nutrients by the mitochondrial electron transport chain ETC is implicated in the aging process. Polymorphisms in core ETC proteins may have an effect on longevity. Here we investigate the cytochrome b cytb polymorphism at amino acid 7 cytbI7T that distinguishes human mitochondrial haplogroup H from haplogroup U.

Principal Findings

We compared longevity of individuals in these two haplogroups during historical extremes of caloric intake. Haplogroup H exhibits significantly increased longevity during historical caloric restriction compared to haplogroup U p = 0.02 while during caloric abundance they are not different. The historical effects of natural selection on the cytb protein were estimated with the software TreeSAAP using a phylogenetic reconstruction for 107 mammal taxa from all major mammalian lineages using 13 complete protein-coding mitochondrial gene sequences. With this framework, we compared the biochemical shifts produced by cytbI7T with historical evolutionary pressure on and near this polymorphic site throughout mammalian evolution to characterize the role cytbI7T had on the ETC during times of restricted caloric intake.

Significance

Our results suggest the relationship between caloric restriction and increased longevity in human mitochondrial haplogroup H is determined by cytbI7T which likely enhances the ability of water to replenish the Qi binding site and decreases the time ubisemiquinone is at the Qo site, resulting in a decrease in the average production rate of radical oxygen species ROS.



Author: Wesley A. Beckstead, Mark T. W. Ebbert, Mark J. Rowe, David A. McClellan

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents