Abstract
BackgroundMutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial dysfunction in aging processes has been the lack of model systems with relevant, naturally occurring mitochondrial genetic variation. Toward the goal of developing such a model system, we studied natural variation in life history, metabolic, and aging phenotypes as it relates to levels of a naturally-occurring heteroplasmic mitochondrial ND5 deletion recently discovered to segregate among wild populations of the soil nematode, Caenorhabditis briggsae. The normal product of ND5 is a central component of the mitochondrial electron transport chain and integral to cellular energy metabolism.ResultsWe quantified significant variation among C. briggsae isolates for all phenotypes measured, only some of which was statistically associated with isolate-specific ND5 deletion frequency. We found that fecundity-related traits and pharyngeal pumping rate were strongly inversely related to ND5 deletion level and that C. briggsae isolates with high ND5 deletion levels experienced a tradeoff between early fecundity and lifespan. Conversely, oxidative stress resistance was only weakly associated with ND5 deletion level while ATP content was unrelated to deletion level. Finally, mean levels of reactive oxygen species measured in vivo showed a significant non-linear relationship with ND5 deletion level, a pattern that may be driven by among-isolate variation in antioxidant or other compensatory mechanisms.ConclusionsOur findings suggest that the ND5 deletion may adversely affect fitness and mitochondrial functioning while promoting aging in natural populations, and help to further establish this species as a useful model for explicit tests of hypotheses in aging biology and mitochondrial genetics.
Highlights
Mutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders
We surveyed variation in life history, physiology, and aging phenotypes among wild C. briggsae isolates that represent the full spectrum of natural variation in NADH dehydrogenase subunit 5 (ND5) deletion frequency (Figure 1B)
When isolates were subdivided into deletion frequency categories (Figure 1B legend), we found that high-ND5 deletion isolates had significantly reduced total fecundities and r compared to either low or zero-deletion isolates (Tukey HSD, a = 0.05; Figure 2A)
Summary
Mutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. Toward the goal of developing such a model system, we studied natural variation in life history, metabolic, and aging phenotypes as it relates to levels of a naturally-occurring heteroplasmic mitochondrial ND5 deletion recently discovered to segregate among wild populations of the soil nematode, Caenorhabditis briggsae. As molecular genetic and genomic approaches have become increasingly available, nematode biologists have become interested in explaining and predicting natural patterns of phenotypic and genomic evolution. Mutations that impair functioning of the mitochondrial electron transport chain (ETC) are associated with a variety of human metabolic and age-related disorders [12,13,14]. Several neurodegenerative disorders including Parkinson’s disease are associated with heteroplasmic ND5 mutations [13]
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