Biology subjects

Dowling, D. K.

Publications and source records attributed to Dowling, D. K..

9 recordsLinked to original sources

bioRxiv2025

Mitochondrial genotype interacts with age and sex, but not nuclear background, to shape locomotory performance across mitonuclear strains of fruit flies

The discovery that mitochondrial genomes can harbor functional mutations despite the evolutionarily conserved role of mitochondria has spurred interest in better understanding the ecological and evolutionary consequences of such mitochondrial genetic variation. Because mitochondrial DNA (mtDNA) encodes products that must function in concert with products of the nuclear genome, and because mitochondria are largely maternally inherited, outstanding questions remain as to how, when, and why variation in mtDNA may affect phenotype. In this study, we developed a set of intraspecific "mitonuclear strains" of Drosophila melanogaster fruit flies that vary across 13 mtDNA haplotypes and 3 nuclear genetic backgrounds. We created a new apparatus called the Drop Tower to test the performance of these strains in negative geotaxis, a locomotory trait we predicted to be sensitive to variation at the level of mitochondria, across both sexes and two age classes. We found that both mitochondrial and nuclear genetic variation significantly altered how negative geotaxis performance changed with age and across the sexes, though interactions between mitochondrial and nuclear strains did not affect performance. Across most strains, male flies performed more poorly and suffered a steeper decline with age than did females, and young males appeared to vary more in performance across mitochondrial strains. In addition, we discovered a strong effect of small differences of parental age on negative geotaxis-- and this effect also varied by mitochondrial strain. Collectively, the results of our study reveal that intraspecific variation in both mitochondrial and nuclear DNA can affect age- and sex-related differences in fruit fly locomotory performance. Further exploring the mechanisms linking these subtle genetic differences to locomotory phenotype and creating differences in response between the sexes will be important to understanding the evolutionary forces shaping the patterns we detected.

evolutionary biology↗

bioRxiv2024

Testing for age- and sex- specific mitonuclear epistasis in Drosophila

The need for efficient ATP production is predicted to result in the evolution of cooperation between the mitochondrial and nuclear encoded components of the electron transport system. Novel (i.e., mismatched) mitonuclear genotype combinations are therefore predicted to result in negative fitness consequences, which may become more prevalent with ageing. Such negative fitness effects are expected to be prominent in males, since maternal inheritance of mitochondria is predicted to lead to accumulation of male-harming mutations (the mothers curse hypothesis). To test these predictions, we measured female and male fertility traits using a genetically diverse panel of 27 mitonuclear populations of Drosophila melanogaster with matched or experimentally mismatched mitonuclear genomes at different ages. We found no overall effect of mitonuclear mismatch. In females, we found no effect of mitonuclear epistasis. In males, we found limited evidence of mitonuclear epistasis affecting fitness in old age, however, not in the direction predicted. Experimentally mismatched males sired more offspring in one comparison. Sex-specific advantages of mismatched males might arise if novel nuclear alleles compensate for deleterious mitochondrial alleles that have accumulated. If such compensatory effects of novel mitonuclear combinations increasing fitness occur in nature, they could represent a possible counterforce to the mothers curse.

evolutionary biology↗

bioRxiv2021

Maternal and paternal sugar consumption interact to modify offspring life history and physiology

Intergenerational effects on offspring phenotypes occur in response to variation in both maternal and paternal nutrition. Because the combined maternal and paternal effects are rarely considered together however, their relative contributions, and the capacity for interactions between parental diets to shape offspring life history and physiology are not understood. To address this, we altered sucrose levels of adult fruit flies (Drosophila melanogaster) prior to mating, across two generations, producing parent-parent and parent-offspring combinations that were either matched or mismatched in dietary sucrose. We then measured lifespan, fecundity, body mass, and triglyceride levels in parents and offspring. We reveal complex non-additive interactions, that involve diets of each parent and offspring to shape offspring phenotypes, but the effects were generally not consistent with an adaptive response to parental diet. Notably, we find that interacting parental flies (sires and dams) lived longer when their sucrose treatments were matched, but they produced shorter-lived offspring.

evolutionary biology↗

bioRxiv2021

Mito-nuclear variation in transgenerational and reproductive effects of amino acid and lipid nutrition

Epistasis between mitochondrial and nuclear genomes can modulate fitness effects of nutrition. Are these "mitonuclear" effects deterministic with regard to optimal nutrition? Which nutrients and genetic loci participate? Here, in fruitflies, we show that mitonuclear epistasis repeatably dictates fitness effects of dietary lipids and amino acids, with a tripartite interaction emerging as an unprecedented source of quantitative variation. We also observed diet-dependent developmental lethality and parental effects, but only in specific mitonucleotypes. Associating phenotype to mtDNA variation implicated a non-coding RNA (mt:lrRNA), suggesting a novel mechanism, with epistasis between mitochondria-derived regulatory factors and the nuclear genome producing qualitative differences in how diet impacts fitness. SUMMARYCombined action of nuclear genotype and regulatory loci on mtDNA produces major differences in fitness impacts of nutrition.

genetics↗

bioRxiv2020

A new member in the Argonaute crew: the mt-miRNAs

Mutations within the mitochondrial genome have been linked to many diverse phenotypes. Moreover, the effects of these mutations have been shown to differ across sexes and environments. The mechanisms that explain the manifold array of mitochondrial genotypic effects on organismal function, and their context-dependency, have however remained a mystery. Here, we present evidence that mitochondria are involved in nuclear gene regulation via RNA interference; transcribing mitochondrial (mt-)miRNAs that may repress the transcription of nuclear genes that previously had no known involvement in mitochondrial function. Our findings uncover a new mechanism by which mitochondria may shape the expression of animal life-histories and health components; implying that the influence of the mitochondria in regulating organismal function extends well beyond the process of energy production.

molecular biology↗

bioRxiv2019

Interactions between cytoplasmic and nuclear genomes confer sex-specific effects on lifespan in Drosophila melanogaster

A large body of studies has demonstrated that genetic variation that resides outside of the cell nucleus can affect the organismal phenotype. The cytoplasm is home to the mitochondrial genome and, at least in arthropods, often hosts intracellular endosymbiotic bacteria such as Wolbachia. While numerous studies have implicated epistatic interactions between cytoplasmic and nuclear genetic variation as key to mediating patterns of phenotypic expression, two outstanding questions remain. Firstly, the relative contribution of mitochondrial genetic variation to other cytoplasmic sources of variation in shaping the phenotypic outcomes of cyto-nuclear interactions remains unknown. Secondly, it remains unclear whether the outcomes of cyto-nuclear interactions will manifest differently across the two sexes, as might be predicted given that cytoplasmic genomes are screened by natural selection only through females as a consequence of their maternal inheritance. Here, we address these questions, creating a fully-crossed set of replicated cyto-nuclear populations derived from three geographically distinct populations of Drosophila melanogaster, and measuring the lifespan of males and females from each population. We report cyto-nuclear interactions for lifespan, with the outcomes of these interactions differing across the sexes, and reconcile these findings with information on the full mitochondrial sequences and Wolbachia infection status of each of the populations.

evolutionary biology↗

bioRxiv2017

Mitochondrial Genetic Effects On Reproductive Success: Signatures Of Positive Intra-Sexual, But Negative Inter-Sexual Pleiotropy

Mitochondria contain their own DNA, and numerous studies have reported that genetic variation in this (mt)DNA sequence modifies the expression of life-history phenotypes. Maternal inheritance of mitochondria adds a layer of complexity to trajectories of mtDNA evolution, because theory predicts the accumulation of mtDNA mutations that are male-biased in effect. While it is clear that mitochondrial genomes routinely harbor genetic variation that affects components of reproductive performance, the extent to which this variation is sex-biased, or even sex-specific in effect, remains elusive. This is because nearly all previous studies have failed to examine mitochondrial genetic effects on both male and female reproductive performance within the one-and-the-same study. Here, we show that variation across naturally-occurring mitochondrial haplotypes affects components of reproductive success in both sexes, in Drosophila melanogaster. However, while we uncovered evidence for positive pleiotropy, across haplotypes, in effects on separate components of reproductive success when measured within the same sex, such patterns were not evident across sexes. Rather, we found a pattern of sexual antagonism across haplotypes on some reproductive parameters. This suggests the pool of polymorphisms that delineate global mtDNA haplotypes is likely to have been partly shaped by maternal transmission of mtDNA and its evolutionary consequences.

evolutionary biology↗

bioRxiv2017

Experimental Evidence That Thermal Selection Shapes Mitochondrial Genome Evolution

Mitochondria are essential organelles, found within eukaryotic cells, which contain their own DNA. Mitochondrial DNA (mtDNA) has traditionally been used in population genetic and biogeographic studies as a maternally-inherited and evolutionary-neutral genetic marker. However, it is now clear that polymorphisms within the mtDNA sequence are routinely non-neutral, and furthermore several studies have suggested that such mtDNA polymorphisms are also sensitive to thermal selection. These observations led to the formulation of the \"mitochondrial climatic adaptation\" hypothesis, for which all published evidence to date is correlational. Here, we use laboratory-based experimental evolution in the fruit fly, Drosophila melanogaster, to test whether thermal selection can shift population frequencies of two mtDNA haplogroups whose natural frequencies exhibit clinal associations with latitude along the Australian east-coast. We present experimental evidence that the thermal regime in which the laboratory populations were maintained, drove changes in haplogroup frequencies across generations. Our results strengthen the emerging view that intra-specific mtDNA variants are sensitive to selection, and suggest spatial distributions of mtDNA variants in natural populations of metazoans might reflect adaptation to climatic environments rather than within-population coalescence and diffusion of selectively-neutral haplotypes across populations.\n\nImpact SummaryWe applied experimental laboratory evolution to provide the first direct test of the \"mitochondrial climatic hypothesis,\" which predicts that the variation of mitochondrial genomes across natural distributions of metazoans can be shaped by thermal selection. Our design is the first of its kind when it comes to inferring the role of thermal selection in shaping mtDNA frequencies in nature. We harness two naturally occurring mtDNA haplotypes of Drosophila melanogaster that segregate along the east coast of Australia. One of these haplotypes predominates at sub-tropical northern latitudes and the other in the temperate and cooler south of the country. We then compete these haplotypes against each other in replicated experimental fly populations submitted to one of four different thermal regimes, in either the presence or absence of infection by Wolbachia, a coevolved endosymbiont that also exhibits maternal transmission.\n\nWe confirm that when evolving in the laboratory under warmer conditions, a haplotype naturally predominating in subtropical conditions outcompetes a haplotype that predominates at cooler Australian latitudes in the wild. We see this effect on haplotype frequencies in females in populations where latent Wolbachia infections had been purged.\n\nOur results also suggest that sex-specificity of mtDNA effects, and co-occurrence of other maternally-inherited microbiotic entities - of which Wolbachia is just one example - are likely to shape the trajectories of mitochondrial genome evolution in the wild.

evolutionary biology↗

bioRxiv2017

Experimental evidence that thermal selection has shaped the latitudinal distribution of mitochondrial haplotypes in Australian fruit flies

Cellular metabolism is regulated by enzyme complexes within the mitochondrion, the function of which are sensitive to the prevailing temperature. Such thermal sensitivity, coupled with the observation that population frequencies of mitochondrial haplotypes tend to associate with latitude, altitude or climatic regions across species distributions, led to the hypothesis that thermal selection has played a role in shaping standing variation in the mitochondrial DNA (mtDNA) sequence. This hypothesis, however, remains controversial, and requires evidence that the distribution of haplotypes observed in nature corresponds with the capacity of these haplotypes to confer differences in thermal tolerance. Specifically, haplotypes predominating in tropical climates are predicted to encode increased tolerance to heat stress, but decreased tolerance to cold stress. We present direct evidence for these predictions, using mtDNA haplotypes sampled from the Australian distribution of Drosophila melanogaster. We show that the ability of flies to tolerate extreme thermal challenges is affected by sequence variation across mtDNA haplotypes, and that the thermal performance associated with each haplotype corresponds with its latitudinal prevalence. The haplotype that predominates at low (subtropical) latitudes confers greater resilience to heat stress, but lower resilience to cold stress, than haplotypes predominating at higher (temperate) latitudes. We explore molecular mechanisms that might underlie these responses, presenting evidence that the effects are in part regulated by SNPs that do not change the protein sequence. Our findings suggest that standing variation in the mitochondrial genome can be shaped by thermal selection, and could therefore contribute to evolutionary adaptation under climatic stress.

evolutionary biology↗