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  1. Article ; Online: Mitochondrial genomic variation drives differential nuclear gene expression in discrete regions of Drosophila gene and protein interaction networks

    Jim A. Mossman / Leann M. Biancani / David M. Rand

    BMC Genomics, Vol 20, Iss 1, Pp 1-

    2019  Volume 23

    Abstract: Abstract Background Mitochondria perform many key roles in their eukaryotic hosts, from integrating signaling pathways through to modulating whole organism phenotypes. The > 1 billion years of nuclear and mitochondrial gene co-evolution has necessitated ... ...

    Abstract Abstract Background Mitochondria perform many key roles in their eukaryotic hosts, from integrating signaling pathways through to modulating whole organism phenotypes. The > 1 billion years of nuclear and mitochondrial gene co-evolution has necessitated coordinated expression of gene products from both genomes that maintain mitochondrial, and more generally, eukaryotic cellular function. How mitochondrial DNA (mtDNA) variation modifies host fitness has proved a challenging question but has profound implications for evolutionary and medical genetics. In Drosophila, we have previously shown that recently diverged mtDNA haplotypes within-species can have more impact on organismal phenotypes than older, deeply diverged haplotypes from different species. Here, we tested the effects of mtDNA haplotype variation on gene expression in Drosophila under standardized conditions. Using the Drosophila Genetic Reference Panel (DGRP), we constructed a panel of mitonuclear genotypes that consists of factorial variation in nuclear and mtDNA genomes, with mtDNAs originating in D. melanogaster (2x haplotypes) and D. simulans (2x haplotypes). Results We show that mtDNA haplotype variation unequivocally alters nuclear gene expression in both females and males, and mitonuclear interactions are pervasive modifying factors for gene expression. There was appreciable overlap between the sexes for mtDNA-sensitive genes, and considerable transcriptional variation attributed to particular mtDNA contrasts. These genes are generally found in low-connectivity gene co-expression networks, occur in gene clusters along chromosomes, are often flanked by non-coding RNA, and are under-represented among housekeeping genes. Finally, we identify the giant (gt) transcription factor motif as a putative regulatory sequence associated with mtDNA-sensitive genes. Conclusions There are predictive conditions for nuclear genes that are influenced by mtDNA variation.
    Keywords Mitonuclear ; mtDNA ; Haplotype ; Gene expression ; Systems biology ; Biotechnology ; TP248.13-248.65 ; Genetics ; QH426-470
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Characterizing the cirri and gut microbiomes of the intertidal barnacle Semibalanus balanoides

    Bianca R. P. Brown / Joaquin C. B. Nunez / David M. Rand

    Animal Microbiome, Vol 2, Iss 1, Pp 1-

    2020  Volume 16

    Abstract: Abstract Background Natural populations inhabiting the rocky intertidal experience multiple ecological stressors and provide an opportunity to investigate how environmental differences influence microbiomes over small geographical scales. However, very ... ...

    Abstract Abstract Background Natural populations inhabiting the rocky intertidal experience multiple ecological stressors and provide an opportunity to investigate how environmental differences influence microbiomes over small geographical scales. However, very few microbiome studies focus on animals that inhabit the intertidal. In this study, we investigate the microbiome of the intertidal barnacle Semibalanus balanoides. We first describe the microbiome of two body tissues: the feeding appendages, or cirri, and the gut. Next, we examine whether there are differences between the microbiome of each body tissue of barnacles collected from the thermally extreme microhabitats of the rocky shores’ upper and lower tidal zones. Results Overall, the microbiome of S. balanoides consisted of 18 phyla from 408 genera. Our results showed that although cirri and gut microbiomes shared a portion of their amplicon sequence variants (ASVs), the microbiome of each body tissue was distinct. Over 80% of the ASVs found in the cirri were also found in the gut, and 44% of the ASVs found in the gut were also found in the cirri. Notably, the gut microbiome was not a subset of the cirri microbiome. Additionally, we identified that the cirri microbiome was responsive to microhabitat differences. Conclusion Results from this study indicate that S. balanoides maintains distinct microbiomes in its cirri and gut tissues, and that the gut microbiome is more stable than the cirri microbiome between the extremes of the intertidal.
    Keywords Barnacles ; Intertidal ; Microbiome ; Semibalanus balanoides ; 16S rRNA gene ; Rocky shore ; Veterinary medicine ; SF600-1100 ; Microbiology ; QR1-502
    Subject code 333
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Mitigating mutational meltdown in mammalian mitochondria.

    David M Rand

    PLoS Biology, Vol 6, Iss 2, p e

    2008  Volume 35

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2008-02-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: A hydrazine coupled cycling assay validates the decrease in redox ratio under starvation in Drosophila.

    Chen-Tseh Zhu / David M Rand

    PLoS ONE, Vol 7, Iss 10, p e

    2012  Volume 47584

    Abstract: A commonly used enzymatic recycling assay for pyridine nucleotides has been adapted to directly measure the NAD(+)/NADH redox ratio in Drosophila melanogaster. This method is also suitable for quantification of NADP(+) and NADPH. The addition of a ... ...

    Abstract A commonly used enzymatic recycling assay for pyridine nucleotides has been adapted to directly measure the NAD(+)/NADH redox ratio in Drosophila melanogaster. This method is also suitable for quantification of NADP(+) and NADPH. The addition of a coupling reaction removing acetaldehyde produced from the alcohol dehydrogenase (ADH) reaction was shown to improve the linearity of NAD(H) assay. The advantages of this assay method are that it allows the determination of both NAD(+) and NADH simultaneously while keeping enzymatic degradation of pyridine nucleotides minimal and also achieving better sensitivity. This method was used to determine the redox ratio of D. melanogaster and validated substantial decrease of redox ratio during starvation.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A Drosophila model for mito-nuclear diseases generated by an incompatible interaction between tRNA and tRNA synthetase

    Marissa A. Holmbeck / Julia R. Donner / Eugenia Villa-Cuesta / David M. Rand

    Disease Models & Mechanisms, Vol 8, Iss 8, Pp 843-

    2015  Volume 854

    Abstract: Communication between the mitochondrial and nuclear genomes is vital for cellular function. The assembly of mitochondrial enzyme complexes, which produce the majority of cellular energy, requires the coordinated expression and translation of both ... ...

    Abstract Communication between the mitochondrial and nuclear genomes is vital for cellular function. The assembly of mitochondrial enzyme complexes, which produce the majority of cellular energy, requires the coordinated expression and translation of both mitochondrially and nuclear-encoded proteins. The joint genetic architecture of this system complicates the basis of mitochondrial diseases, and mutations both in mitochondrial DNA (mtDNA)- and nuclear-encoded genes have been implicated in mitochondrial dysfunction. Previously, in a set of mitochondrial-nuclear introgression strains, we characterized a dual genome epistasis in which a naturally occurring mutation in the Drosophila simulans simw501 mtDNA-encoded transfer RNA (tRNA) for tyrosine (tRNATyr) interacts with a mutation in the nuclear-encoded mitochondrially localized tyrosyl-tRNA synthetase from Drosophila melanogaster. Here, we show that the incompatible mitochondrial-nuclear combination results in locomotor defects, reduced mitochondrial respiratory capacity, decreased oxidative phosphorylation (OXPHOS) enzyme activity and severe alterations in mitochondrial morphology. Transgenic rescue strains containing nuclear variants of the tyrosyl-tRNA synthetase are sufficient to rescue many of the deleterious phenotypes identified when paired with the simw501 mtDNA. However, the severity of this defective mito-nuclear interaction varies across traits and genetic backgrounds, suggesting that the impact of mitochondrial dysfunction might be tissue specific. Because mutations in mitochondrial tRNATyr are associated with exercise intolerance in humans, this mitochondrial-nuclear introgression model in Drosophila provides a means to dissect the molecular basis of these, and other, mitochondrial diseases that are a consequence of the joint genetic architecture of mitochondrial function.
    Keywords Disease ; Epistasis ; Mitochondria ; Medicine ; R ; Pathology ; RB1-214
    Subject code 570
    Language English
    Publishing date 2015-08-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Silver nanoparticle toxicity in Drosophila

    Deborah J Gorth / David M Rand / Thomas J Webster

    International Journal of Nanomedicine, Vol 2011, Iss default, Pp 343-

    size does matter

    2011  Volume 350

    Abstract: Deborah J Gorth1, David M Rand2, Thomas J Webster11School of Engineering, 2Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, USABackground: Consumer nanotechnology is a growing industry. Silver nanoparticles are the most ... ...

    Abstract Deborah J Gorth1, David M Rand2, Thomas J Webster11School of Engineering, 2Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, USABackground: Consumer nanotechnology is a growing industry. Silver nanoparticles are the most common nanomaterial added to commercially available products, so understanding the influence that size has on toxicity is integral to the safe use of these new products. This study examined the influence of silver particle size on Drosophila egg development by comparing the toxicity of both nanoscale and conventional-sized silver particles.Methods: The toxicity assays were conducted by exposing Drosophila eggs to particle concentrations ranging from 10 ppm to 100 ppm of silver. Size, chemistry, and agglomeration of the silver particles were evaluated using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering.Results: This analysis confirmed individual silver particle sizes in the ranges of 20–30 nm, 100 nm, and 500–1200 nm, with similar chemistry. Dynamic light scattering and transmission electron microscope data also indicated agglomeration in water, with the transmission electron microscopic images showing individual particles in the correct size range, but the dynamic light scattering z-average sizes of the silver nanoparticles were 782 ± 379 nm for the 20–30 nm silver nanoparticles, 693 ± 114 nm for the 100 nm silver nanoparticles, and 508 ± 32 nm for the 500–1200 nm silver particles. Most importantly, here we show significantly more Drosophila egg toxicity when exposed to larger, nonnanometer silver particles. Upon exposure to silver nanoparticles sized 20–30 nm, Drosophila eggs did not exhibit a statistically significant (P < 0.05) decrease in their likelihood to pupate, but eggs exposed to larger silver particles (500–1200 nm) were 91% ± 18% less likely to pupate. Exposure to silver nanoparticles reduced the percentage of pupae able to emerge as adults. At 10 ppm of silver particle exposure, only 57% ± 48% of ...
    Keywords Medicine (General) ; R5-920
    Subject code 550
    Language English
    Publishing date 2011-02-01T00:00:00Z
    Publisher Dove Medical Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: The spectrum of mitochondrial mutation differs across species.

    Kristi L Montooth / David M Rand

    PLoS Biology, Vol 6, Iss 8, p e

    2008  Volume 213

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2008-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Stable genetic structure and connectivity in pollution-adapted and nearby pollution-sensitive populations of Fundulus heteroclitus

    Joaquin C. B. Nunez / Leann M. Biancani / Patrick A. Flight / Diane E. Nacci / David M. Rand / Douglas L. Crawford / Marjorie F. Oleksiak

    Royal Society Open Science, Vol 5, Iss

    2018  Volume 5

    Abstract: Populations of the non-migratory estuarine fish Fundulus heteroclitus inhabiting the heavily polluted New Bedford Harbour (NBH) estuary have shown inherited tolerance to local pollutants introduced to their habitats in the past 100 years. Here we examine ...

    Abstract Populations of the non-migratory estuarine fish Fundulus heteroclitus inhabiting the heavily polluted New Bedford Harbour (NBH) estuary have shown inherited tolerance to local pollutants introduced to their habitats in the past 100 years. Here we examine two questions: (i) Is there pollution-driven selection on the mitochondrial genome across a fine geographical scale? and (ii) What is the pattern of migration among sites spanning a strong pollution gradient? Whole mitochondrial genomes were analysed for 133 F. heteroclitus from seven nearby collection sites: four sites along the NBH pollution cline (approx. 5 km distance), which had pollution-adapted fish, as well as one site adjacent to the pollution cline and two relatively unpolluted sites about 30 km away, which had pollution-sensitive fish. Additionally, we used microsatellite analyses to quantify genetic variation over three F. heteroclitus generations in both pollution-adapted and sensitive individuals collected from two sites at two different time points (1999/2000 and 2007/2008). Our results show no evidence for a selective sweep of mtDNA in the polluted sites. Moreover, mtDNA analyses revealed that both pollution-adapted and sensitive populations harbour similar levels of genetic diversity. We observed a high level of non-synonymous mutations in the most polluted site. This is probably associated with a reduction in Ne and concomitant weakening of purifying selection, a demographic expansion following a pollution-related bottleneck or increased mutation rates. Our demographic analyses suggest that isolation by distance influences the distribution of mtDNA genetic variation between the pollution cline and the clean populations at broad spatial scales. At finer scales, population structure is patchy, and neither spatial distance, pollution concentration or pollution tolerance is a good predictor of mtDNA variation. Lastly, microsatellite analyses revealed stable population structure over the last decade.
    Keywords genetic variation ; mtdna ; snp ; microsatellites ; population genetics ; pollution cline ; Science ; Q
    Subject code 333
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher The Royal Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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