Drosophila melanogaster as a Model System to Study Mitochondrial Biology

Fernández-Moreno, Miguel Ángel; Farr, Carol L.; Kaguni, Laurie S.; Garesse, Rafael

doi:10.1007/978-1-59745-365-3_3

Cited by 64 publications

(58 citation statements)

References 9 publications

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“…As expected from previous studies, 15,20 the SNPs are not homogenously distributed in the euchromatin. The SNPs on the autosome arms (2L, 2R, 3L and 3R) are almost twice as frequent as the SNPs on the X (0.35% versus 0.19%, respectively).…”

Section: Resultssupporting

confidence: 88%

“…10,15,20 Alternatively, an undefined hyper-mutation mechanism (such as via recombination hotspots) might account for SNP hotspots in sensory perception genes. For example, there might be an epigenetic mechanism that increases the random mutation frequency (via increasing recombination frequency) in evolutionarily-important genes, such as we propose in the Epigenetic Directed Genetic Error (EDGE) hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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Massively parallel resequencing of the isogenicDrosophila melanogasterstrain w1118; iso-2; iso-3 identifies hotspots for mutations in sensory perception genes

Platts¹,

Land²,

Chen³

et al. 2009

Fly

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We used the Illumina reversible-short sequencing technology to obtain 17-fold average depth (s.d. ~8) of ~94% of the euchromatic genome and ~1–5% of the heterochromatin sequence of the Drosophila melanogaster isogenic strain w1118; iso-2; iso-3. We show that this strain has a ~9 kb deletion that uncovers the first exon of the white (w) gene, ~4 kb of downstream promoter sequences, and most of the first intron, thus demonstrating that whole-genome sequencing can be used for mutation characterization. We chose this strain because there are thousands of transposon insertion lines and hundreds of isogenic deficiency lines available with this genetic background, such as the Exelixis, Inc., and the DrosDEL collections. We compared our sequence to Release 5 of the finished reference genome sequence which was made from the isogenic strain y1; cn1 bw1 sp1 and identified 356,614 candidate SNPs in the ~117 Mb unique sequence genome, which represents a substitution rate of ~1/305 nucleotides (~0.30%). The distribution of SNPs is not uniform, but rather there is a ~2-fold increase in SNPs on the autosome arms compared with the X chromosome and a ~7-fold increase when compared to the small 4th chromosome. This is consistent with previous analyses that demonstrated a correlation between recombination frequency and SNP frequency. An unexpected finding was a SNP hotpot in a ~20 Mb central region of the 4th chromosome, which might indicate higher than expected recombination frequency in this region of this chromosome. Interestingly, genes involved in sensory perception are enriched in SNP hotspots and genes encoding developmental genes are enriched in SNP coldspots, which suggests that recombination frequencies might be proportional to the evolutionary selection coefficient. There are currently 12 Drosophila species sequenced, and this represents one of many isogenic Drosophila melanogaster genome sequences that are in progress. Because of the dramatic increase in power in using isogenic lines rather than outbred individuals, the SNP information should be valuable as a test bed for understanding genotype-by-environment interactions in human population studies.

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Section: Resultssupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Massively parallel resequencing of the isogenicDrosophila melanogasterstrain w1118; iso-2; iso-3 identifies hotspots for mutations in sensory perception genes

Platts¹,

Land²,

Chen³

et al. 2009

Fly

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“…Recently, Drosophila melanogaster has proven a powerful tool in uncovering the molecular mechanisms involved in several human metabolic diseases – in fact an average of 75% of the known human disease-related genes are conserved in the fly (Reiter et al , 2001; Sanchez-Martinez et al , 2006; Baker and Thummel, 2007; Fernández-Moreno et al , 2007; Birse et al , 2010; Musselman et al , 2011; Na et al , 2013). Methods exist in the fly for the analysis of metabolic profiles including measurement of circulating and stored lipids and carbohydrates and ATP levels as well as tools for metabolomics (Tennessen et al , 2014).…”

Section: Benefits Of the Drosophila Model In Metabolic Studiesmentioning

confidence: 99%

Modeling dietary influences on offspring metabolic programming in Drosophila melanogaster

Brookheart¹,

Duncan²

2016

Reproduction

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The influence of nutrition on offspring metabolism has become a hot topic in recent years owing to the growing prevalence of maternal and childhood obesity. Studies in mammals have identified several factors correlating with parental and early offspring dietary influences on progeny health; however, the molecular mechanisms that underlie these factors remain undiscovered. Mammalian metabolic tissues and pathways are heavily conserved in Drosophila melanogaster, making the fly an invaluable genetic model organism for studying metabolism. In this review, we discuss the metabolic similarities between mammals and Drosophila and present evidence supporting its use as an emerging model of metabolic programming.Reproduction (2016) 152 R79-R90

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“…It is important to note the striking conservation of some biological processes from flies to humans. When a Drosophila homolog of an essential but poorly understood mammalian gene is identified, as happens with a large number of mitochondrial genes, powerful genetic and molecular techniques available in Drosophila can be applied to its characterization (17). …”

Section: Introductionmentioning

confidence: 99%

Comparative Purification Strategies for Drosophila and Human Mitochondrial DNA Replication Proteins: DNA Polymerase γ and Mitochondrial Single-Stranded DNA-Binding Protein

Oliveira

Kaguni

2009

Methods in Molecular Biology

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The mitochondrion is the eukaryotic organelle that carries out oxidative phosphorylation, fulfilling cellular requirements for ATP production. Disruption of mitochondrial energy metabolism can occur by genetic and biochemical mechanisms involving nuclear-encoded proteins that are required at the mitochondrial DNA replication fork, which often leads to human disorders and to animal lethality during development. DNA polymerase γ (pol γ), the mitochondrial replicase, and the mitochondrial single-stranded DNA-binding protein (mtSSB) have been the focus of study in our lab for a number of years. Here we describe the purification strategies that we developed for obtaining the recombinant forms of pol γ and mtSSB from both Drosophila melanogaster and humans. Despite the fact that similar approaches can be used for purifying the homologous proteins, we have observed that there are differences in the behavior of the proteins in some specific steps that may reflect differences in their structural and biochemical properties. Their purification in homogeneous, active form represents the first step toward our long-term goal to understand their biochemistry, biology, and functions at the mitochondrial DNA replication fork.

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Drosophila melanogaster as a Model System to Study Mitochondrial Biology

Cited by 64 publications

References 9 publications

Massively parallel resequencing of the isogenicDrosophila melanogasterstrain w1118; iso-2; iso-3 identifies hotspots for mutations in sensory perception genes

Massively parallel resequencing of the isogenicDrosophila melanogasterstrain w1118; iso-2; iso-3 identifies hotspots for mutations in sensory perception genes

Modeling dietary influences on offspring metabolic programming in Drosophila melanogaster

Comparative Purification Strategies for Drosophila and Human Mitochondrial DNA Replication Proteins: DNA Polymerase γ and Mitochondrial Single-Stranded DNA-Binding Protein

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