Mitochondrial Optimization May Be Linked to Human Longevity

Boston, MA October 11, 2005 A gradual optimization of mitochondria--the cells' powerhouses--may have occurred in the human lineage, which could be associated with the evolution of human longevity and intelligence. The study, led by Joao Pedro de Magalhaes from Harvard Medical School, is reported in the latest issue of the Journal of Molecular Evolution.

By comparing the mitochondrial genome of multiple primates, the researcher found several mitochondrial genes in which the normal form, or allele, of the gene in nonhuman primates is a disease-causing allele in humans. "What the results show is that certain alleles that cause diseases in humans are predominant in nonhuman primates," says de Magalhaes. "Certainly, some of these alleles do not cause diseases in nonhuman primates and hence secondary changes must have compensated for their deleterious effects. Still, these secondary changes could indicate adaptive differences between humans and nonhuman primates in the mitochondrion." Moreover, the researcher also found normal alleles in nonhuman primates that are associated with human late-onset diseases. It is possible that these late-onset disease-causing alleles are biologically significant, but since nonhuman primates do not live nearly as long as we do they do not develop the diseases. During the evolution of the human species, in which our lifespan was gradually extended, these disease-causing alleles had to be excluded from the population, which could have led to an optimization of the mitochondrion in humans.

Humans are not only the smartest primates but have the longest lifespan, and hence these results could indicate a gradual optimization of mitochondrial proteins in the lineage leading to humans as a means to delay certain forms of neurodegeneration. "It has long been argued that longevity and intelligence evolved together in the lineage leading to humans," says de Magalhaes. "In fact, some nonhuman primates develop neurodegenerative changes at considerably earlier ages than what is typically observed in human patients. Mitochondria have been associated with neurodegenerative diseases, including the genes whose human disease-causing allele was found to be the normal allele in some nonhuman primates, and the mitochondrial genome has be linked to aging. So the general pattern of these results could indicate a selection on the human mitochondrion associated with the higher human intelligence and extended lifespan. Still," de Magalhaes warns, "we will need more detailed studies to prove this hypothesis."

One reason for the researcher's caution is that the mitochondrial genome encodes only a fraction of all mitochondrial proteins. Besides, further work is necessary to assess the exact biological significance of these findings. "The results show a statistically significant general pattern of selection on the mitochondrion in the lineage leading to humans, which may be associated with human longevity and the need to delay the onset of neurodegenerative changes, but they do not tell us which exact molecular changes are biologically significant. That will require a different, more detailed, type of approach and further genomic or biological data."


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