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• 1. [Article] Causes and Consequences of Mitochondrial Variation in Caenorhabditid Nematodes

  Mitochondria are dynamic organelles that harbor their own stream-lined genome and generate much of the ATP necessary to sustain eukaryotic life via an electron transport chain (ETC). Because of the central ...

  Citation × Citation Citation Abstract Copy Title: Causes and Consequences of Mitochondrial Variation in Caenorhabditid Nematodes Author: Hicks, Kiley Ann Year: 2012 Mitochondria are dynamic organelles that harbor their own stream-lined genome and generate much of the ATP necessary to sustain eukaryotic life via an electron transport chain (ETC). Because of the central role for mitochondria in organismal physiology, mitochondrial genetic and phenotypic variation can alter organismal fitness and affect population genetic and evolutionary outcomes. Despite the far-reaching relevance of mitochondria to evolutionary processes and human health, we lack a basic understanding of the causes and consequences of mitochondrial genetic and phenotypic variation. In this thesis, I quantified mitochondrial reactive oxygen species (ROS), membrane potential (δΨM), and mitochondrial morphological traits within Caenorhabditis briggsae natural isolates and mutation-accumulation (MA) lines of both C. briggsae and Caenorhabditis elegans. Substantial natural variation was discovered for most mitochondrial form and function traits measured for a set of C. briggsae isolates known to harbor mitochondrial DNA structural variation in the form of a heteroplasmic nad5 gene deletion (nad5δ) that correlates negatively with organismal fitness. Most among-isolate phenotypic variation could be accounted for by phylogeographic clade membership rather than nad5δ level. Analysis of mitochondrial-nuclear hybrid strains provided support for both mtDNA and nuclear genetic variation as drivers of natural mitochondrial phenotype variation. An MA experimental approach revealed that average levels of both ROS and nad5δ heteroplasmy evolved in remarkably linear ways in C. briggsae maintained under extreme inbreeding. In particular, among C. briggsae isolates prone to acquiring the nad5δ deletion, nad5δ level increased to a plateau of ~50% during successive generations of MA treatment. Conversely, mitochondrial ROS level increased or declined in a strain-specific fashion, which also meant that the relationship between ROS and nad5δ was strain-specific. Further, all lines generated from the isolate with the highest starting level of nad5δ heteroplasmy went extinct prior to generation 20 of MA treatment. Patterns of among-line variance in ROS level were also strain-specific but generally did not conform to the canonical pattern of increasing among-line variance expected for MA experiments. MA lines of C. elegans that had previously been subjected to whole-genome sequencing were found to vary significantly in ROS levels but not in 8-oxo-dG content. Despite a significant positive correlation between 8-oxo-dG and ROS levels, no relationship between oxidative stress measures and base substitution rate or G-to-T transversion rate was revealed. Finally, analysis of patterns of phenotypic correlation for a suite of 24 mitochondrial traits measured in C. briggsae natural isolates support a role for ΔΨM in shaping mitochondrial dynamics, but no such role for mitochondrial ROS. Further, our study suggests a novel model of mitochondrial population dynamics dependent upon cellular environmental context and with implications for mitochondrial genome integrity. This work identifies extensive natural variation and capacity for evolution in organellar traits within multicellular eukaryotic species, with a central role for δΨM in mitochondrial dynamics that may have implications for evolutionary adaptation to thermal niches. Title: Causes and Consequences of Mitochondrial Variation in Caenorhabditid Nematodes Author: Hicks, Kiley Ann Year: 2012 Mitochondria are dynamic organelles that harbor their own stream-lined genome and generate much of the ATP necessary to sustain eukaryotic life via an electron transport chain (ETC). Because of the central role for mitochondria in organismal physiology, mitochondrial genetic and phenotypic variation can alter organismal fitness and affect population genetic and evolutionary outcomes. Despite the far-reaching relevance of mitochondria to evolutionary processes and human health, we lack a basic understanding of the causes and consequences of mitochondrial genetic and phenotypic variation. In this thesis, I quantified mitochondrial reactive oxygen species (ROS), membrane potential (δΨM), and mitochondrial morphological traits within Caenorhabditis briggsae natural isolates and mutation-accumulation (MA) lines of both C. briggsae and Caenorhabditis elegans. Substantial natural variation was discovered for most mitochondrial form and function traits measured for a set of C. briggsae isolates known to harbor mitochondrial DNA structural variation in the form of a heteroplasmic nad5 gene deletion (nad5δ) that correlates negatively with organismal fitness. Most among-isolate phenotypic variation could be accounted for by phylogeographic clade membership rather than nad5δ level. Analysis of mitochondrial-nuclear hybrid strains provided support for both mtDNA and nuclear genetic variation as drivers of natural mitochondrial phenotype variation. An MA experimental approach revealed that average levels of both ROS and nad5δ heteroplasmy evolved in remarkably linear ways in C. briggsae maintained under extreme inbreeding. In particular, among C. briggsae isolates prone to acquiring the nad5δ deletion, nad5δ level increased to a plateau of ~50% during successive generations of MA treatment. Conversely, mitochondrial ROS level increased or declined in a strain-specific fashion, which also meant that the relationship between ROS and nad5δ was strain-specific. Further, all lines generated from the isolate with the highest starting level of nad5δ heteroplasmy went extinct prior to generation 20 of MA treatment. Patterns of among-line variance in ROS level were also strain-specific but generally did not conform to the canonical pattern of increasing among-line variance expected for MA experiments. MA lines of C. elegans that had previously been subjected to whole-genome sequencing were found to vary significantly in ROS levels but not in 8-oxo-dG content. Despite a significant positive correlation between 8-oxo-dG and ROS levels, no relationship between oxidative stress measures and base substitution rate or G-to-T transversion rate was revealed. Finally, analysis of patterns of phenotypic correlation for a suite of 24 mitochondrial traits measured in C. briggsae natural isolates support a role for ΔΨM in shaping mitochondrial dynamics, but no such role for mitochondrial ROS. Further, our study suggests a novel model of mitochondrial population dynamics dependent upon cellular environmental context and with implications for mitochondrial genome integrity. This work identifies extensive natural variation and capacity for evolution in organellar traits within multicellular eukaryotic species, with a central role for δΨM in mitochondrial dynamics that may have implications for evolutionary adaptation to thermal niches. Close