Naturally Occurring Mitochondrial Dna Haplotypes Exhibit Metabolic Differences: Insight Into Functional Properties of Mitochondria (original) (raw)
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Evolution, 2007
Recent studies have used a variety of theoretical arguments to show that mitochondrial (mt) DNA rarely evolves as a strictly neutral marker and that selection operates on the mtDNA of many species. However, the vast majority of researchers are not convinced by these arguments because data linking mtDNA variation with phenotypic differences are limited. We investigated sequence variation in the three mtDNA and nine nuclear genes (including all isoforms) that encode the 12 subunits of cytochrome c oxidase of the electron transport chain in Drosophila. We then studied cytochrome c oxidase activity as a key aspect of mitochondrial bioenergetics and four life-history traits. In Drosophila simulans, sequence data from the three mtDNA encoded cytochrome c oxidase genes show that there are 76 synonymous and two nonsynonymous fixed differences among flies harboring siII compared with siIII mtDNA. In contrast, 13 nuclear encoded genes show no evidence of genetic subdivision associated with the mtDNA. Flies with siIII mtDNA had higher cytochrome c oxidase activity and were more starvation resistant. Flies harboring siII mtDNA had greater egg size and fecundity, and recovered faster from cold coma. These data are consistent with a causative role for mtDNA variation in these phenotypic differences, but we cannot completely rule out the involvement of nuclear genes. The results of this study have significant implications for the use of mtDNA as an assumed neutral marker and show that evolutionary shifts can involve changes in mtDNA despite the small number of genes encoded in the organelle genome.
Mitochondrial DNA variants influence mitochondrial bioenergetics in Drosophila melanogaster
Mitochondrion, 2012
The influence of mitochondrial DNA (mtDNA) mutations on human disease has been extensively studied, but the impact of mutations within the adaptive range is debated. We studied males from lines of Drosophila melanogaster that have a highly standardized nuclear genome but different mtDNA, at two ages. We measured mitochondrial respiration on permeabilized muscle fibers, hydrogen peroxide production of isolated mitochondria and mtDNA copy number of whole individuals. The results show that a small set of naturally occurring mtDNA mutations can have a significant influence on mitochondrial bioenergetics that may change as the organism ages.
Insect Biochemistry and Molecular Biology, 2007
The primary causes of age related changes in mitochondrial metabolism are not known. The goal of this study is to document the influence of naturally occurring mtDNA variation on age dependent changes in mitochondrial respiration, hydrogen peroxide (H 2 O 2 ) generation and antioxidant defenses in the fly Drosophila simulans. Possible changes include an increase in rates of reactive oxygen species production with age and/or an age dependent decrease in antioxidant response. For this study we have used flies harboring distinct siII and siIII mtDNA types. Previously we have shown that males harboring siII mtDNA had higher rates 30 of mitochondrial H 2 O 2 production from complex III at 11 d compared to males with the siIII mtDNA type. Here, we corroborate those results and show that Drosophila harboring the siII and siIII mtDNA types exhibit significantly different patterns of pro-oxidant and antioxidant activities as they age. Flies harboring siII mtDNA had higher rates of mitochondrial H 2 O 2 production and manganese superoxide dismutase activity at 11 and 18 d of age than siIII mtDNA 35 harboring flies. Copper-zinc superoxide dismutase activity increased from 11 to 25 d in siII flies while the accumulation of oxidized glutathione did not change between 11 and 25 d. In contrast, siIII harboring flies showed an age dependent increase in H 2 O 2 production, reaching higher production rates on day 25 than that observed in siII flies. Copper-zinc superoxide dismutase activities did not change between 11 and 25 d while the oxidized glutathione accumulation increased with age. The results show antioxidant levels correlate with pro-oxidant levels in siII but not siIII flies. These results demonstrate our ability to correlate mtDNA variation with differences in whole mitochondrial physiology and individual complex biochemistry.
PloS one, 2017
Here we determine the sex-specific influence of mtDNA type (mitotype) and diet on mitochondrial functions and physiology in two Drosophila melanogaster lines. In many species, males and females differ in aspects of their energy production. These sex-specific influences may be caused by differences in evolutionary history and physiological functions. We predicted the influence of mtDNA mutations should be stronger in males than females as a result of the organelle's maternal mode of inheritance in the majority of metazoans. In contrast, we predicted the influence of diet would be greater in females due to higher metabolic flexibility. We included four diets that differed in their protein: carbohydrate (P:C) ratios as they are the two-major energy-yielding macronutrients in the fly diet. We assayed four mitochondrial function traits (Complex I oxidative phosphorylation, reactive oxygen species production, superoxide dismutase activity, and mtDNA copy number) and four physiological...
Linking the mitochondrial genotype to the organismal phenotype
Molecular Ecology, 2010
One of the grand challenges of the postgenomics era is to mechanistically link the genotype with the phenotype. Here, we consider the link between the mitochondrial genotype and the organismal phenotype that is provided by bioenergetic studies of the electron transport chain. That linkage is pertinent for the fields of molecular ecology and phylogeography as it tests if, and potentially how, natural selection can influence the evolutionary and demographic past of both populations and species. We introduce the mitochondrial genotype in terms of mitochondrial-encoded genes, nuclear-encoded genes that produce structural proteins imported into the mitochondria, and mitochondrial DNA-nuclear interactions. We then review the potential for quaternary structure modelling to predict the functional consequence of specific naturally occurring mutations. We discuss how the energy-producing reactions of oxidative phosphorylation can be used to provide a mechanistic biochemical link between genotype and phenotype. Experimental manipulations can then be used to test the functional consequences of specific mutations in multiple genetic backgrounds. Finally, we examine how mitochondria can influence the organismal mitochondrial phenotype using the examples of lifespan, fertility and starvation resistance and discuss how mitochondria may be involved in establishing both the upper and lower thermal limits of organisms. We conclude that mitochondrial DNA mutations can be important in determining aspects of organism life history. The question that remains to be resolved is how common are these adaptive mutations?
Variation of the Mitochondral Genome in the Evolution of Drosophila
2002
The evidence on mitochondrial genome variation and its role in evolution of the genus Drosophila are reviewed. The mitochondrial genome is represented by a circular double-stranded DNA molecule 16 to 19 kb in length. Mitochondrial genes lack introns and recombination. The entire mitochondrial genome can be arbitrarily divided into three parts: (1) protein-coding genes; (2) genes encoding rRNA and tRNA; and (3) the noncoding regulatory region (A + T region). The selective importance of mutations within different mtDNA regions is therefore unequal. In Drosophila , the content of the A + T pairs in mtDNA is extremely high and a pattern of nucleotide substitution is characterized by a low transition/transversion ratio (and a low threshold of mutation saturation). The deletions and duplications are of common occurrence in the mitochondrial genome. However, this genome lacks such characteristic for the nuclear genome aberrations as inversions and transpositions. The phenomena of introgression and heteroplasmy provide an opportunity to study the adaptive role of the mitochondrial genome and its role in speciation. Analysis of evidence concerning mtDNA variation in different species of the genus Drosophila made it possible to ascertain data on phylogenetic relationships among species obtained by studying nuclear genome variation. In some species, mtDNA variation may serve as a reliable marker for population differentiation within a species, although evidence on the population dynamics of the mtDNA variation is very scarce.
Within-population genetic effects of mtDNA on metabolic rate in Drosophila subobscura
Journal of Evolutionary Biology, 2015
The effects of mtDNA on metabolic rate Abstract A growing body of research supports the view that within-species sequence variation in the mitochondrial genome (mtDNA) is functional, in the sense that it has important phenotypic effects. However, most of this empirical foundation is based on comparisons across populations and few studies have addressed the functional significance of mtDNA polymorphism within populations. Here, using mitonuclear introgression lines, we assess differences in whole organism metabolic rate of adult Drosophila subobscura fruit flies carrying either of three different sympatric mtDNA haplotypes. We document sizeable, up to 20%, differences in metabolic rate across these mtDNA haplotypes.
Comparative genomics of mitochondrial DNA in Drosophila simulans
2000
The current study compares the nucleotide variation among 22 complete mitochondrial genomes of the three distinct Drosophila simulans haplotypes with intron 1 of the alcohol dehydrogenase-related locus. This is the first study to investigate the sequence variation of multiple complete mitochondrial genomes within distinct mitochondrial haplotypes of a single species. Patterns of variation suggest distinct forces are influencing the evolution of mitochondrial DNA (mtDNA) and autosomal DNA in D. simulans. First, there is little variation within each mtDNA haplotype but strong differentiation among them. In contrast, there is no support for differentiation of the mitochondrial haplotypes at the autosomal locus. Second, there is a significant deficiency of mitochondrial variation in each haplotype relative to the autosomal locus. Third, the ratio of nonsynonymous to synonymous substitutions is not equal in all branches of the well-resolved phylogeny. There is an excess of nonsynonymous substitutions relative to synonymous substitutions within each D. simulans haplotype. This result is similar to that previously observed within the mtDNA of distinct species. A single evolutionary force may be causally linked to the observed patterns of mtDNA variation-a rickettsia-like microorganism, Wolbachia pipientis, which is known to directly influence mitochondrial evolution but have a less direct influence on autosomal loci.
Mitochondrial DNA: more than an evolutionary bystander
Functional Ecology, 2014
1. The vast majority of studies employing mtDNA in evolutionary biology and ecology have used it as a means to infer demographic and historical patterns without pondering the underlying functional implications. In contrast, the biochemical and medical communities often aim to understand the influence of specific mtDNA mutations on mitochondrial functions, but rarely consider the evolutionary and ecological implications.
General characteristics of mitochondria and mitochondrial DNA
Mitochondria are cellular organelles that have the function of the oxidative phosphorilation and the formation of ATP. In humans, the mtDNA is a double-stranded, circular, covalent closed molecule of 16.5 kb. The mtDNA is inherited as a haploid from the mother and heteroplasmy has been found rarely. From a populational perspective, it could be considered as a system of small, sexually isolated demes, or clonal lineages, with an evolutionary rate 5 to 10 times faster than the nuclear genome. All these characteristics make this molecule ideal for evolutionary studies. We present two applications of this molecule in genetical studies. One of these is referred to the Balearic Islands populations, Majorca, Minorca, Ibiza, and Chuetas. The other example is the populational dynamics of the different mitochondrial haplotypes in Drosophila subobscura. We also discuss the importance of nuclear markers to complete these studies as well as the study of the Y chromosome to compensate the bias produced by the study of only the mtDNA.