Evolutionary pressure on mitochondrial cytochrome b is consistent with a role of CytbI7T affecting longevity during caloric restriction.
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.


RESULTS
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.


CONCLUSIONS
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 Q(i) binding site and decreases the time ubisemiquinone is at the Q(o) site, resulting in a decrease in the average production rate of radical oxygen species (ROS).
Beckstead
Wesley A
WA
Department of Biology, Brigham Young University, Provo, Utah, United States of America.
Ebbert
Mark T W
MT
Rowe
Mark J
MJ
McClellan
David A
DA
D000375:Aging; D001665:Binding Sites; D031204:Caloric Restriction; D045303:Cytochromes b / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005609:Free Radicals; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism*; D008957:Models, Genetic; D008968:Molecular Conformation; D010802:Phylogeny; D011110:Polymorphism, Genetic
D004272:DNA, Mitochondrial; D005609:Free Radicals; D045303:Cytochromes b