Evolution of Mitochondrial Disorders:
Levels of selection, parasitic and altruistic mitochondria in yeast.

Mitochondrial disorders are recognized as the cause of an increasingly large number of progressive genetic diseases in humans, including Leber’s hereditary optic neuropathy, Kearns-Sayre syndrome, cancer and senescence. Mitochondrial disorders are not unique to humans. In plants, mitochondrial DNA (mtDNA) rearrangements can cause male-sterility, a trait that has been put to widespread use in the production of hybrid seed. In some fungi, plasmids formed from mtDNA increase in copy number during somatic growth, resulting in senescence.

Some mitochondrial defects may accumulate because mutant mitochondrial chromosomes have a fitness advantage over functional mitochondrial genomes within cells. Selection among the replicating genomes may favor fast replicating variants, even if they are deleterious to the cell in which they reside. The mutant mitochondria may be held in check by natural selection among cells, or among whole organisms, favoring efficient respiration. Syndromes caused by the accumulation of mutant mitochondria would then be expected to arise when selection among cells, tissues or organisms is relaxed and mitochondrial evolution is driven by selection within cells. This model of parasitic versus altruistic mitochondrial genomes is analogous to other classic examples of conflicting levels of selection, such as the evolution of cooperative (or altruistic) social behaviors that reduce the fitness of individuals within groups relative to selfishness, but which increase the relative fitness of cooperative social groups.

In a collabortion with Cliff Zeyl. at Wake Forest University (From whom I stole the yeast pic above), we developed a mathematical model of this process and tested the model using experimental populations of Saccharomyces cerevisiae. We showed that mitochondrial defects only accumulated in small populations, where among-cell selection favoring cells that can respire was reduced relative to within-cell selection favoring parasitic mitochondria. The accumulation of some mitochondrial defects is therefore an evolutionary process, involving multiple levels of selection. The relative intensities of within- and among cell selection may also explain the tissue specificity of human mitochondrial defects. Although we are not actively working on this system right now, it is reflective of our general interest in understanding the conditions under which selection at higher levels of organization subsumes, or is undermined by, selection among entities at lower levels of organization.

Publications

• Taylor, D.R., Zeyl, C. and E. Cooke, 2002. Conflicting levels of selection and the accumulation of mitochondrial defects in Saccharomyces cerevisiae. Proc. Nat. Acad. Sci.

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