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dc.contributor.authorAw, WC
dc.contributor.authorTowarnicki, SG
dc.contributor.authorMelvin, RG
dc.contributor.authorYoungson, NA
dc.contributor.authorGarvin, MR
dc.contributor.authorHu, Y
dc.contributor.authorNielsen, S
dc.contributor.authorThomas, T
dc.contributor.authorPickford, R
dc.contributor.authorBustamante, S
dc.contributor.authorVila-Sanjurjo, A
dc.contributor.authorSmyth, GK
dc.contributor.authorBallard, JWO
dc.date.accessioned2020-12-09T23:52:41Z
dc.date.available2020-12-09T23:52:41Z
dc.date.issued2018-11-01
dc.identifierpii: PGENETICS-D-18-01077
dc.identifier.citationAw, W. C., Towarnicki, S. G., Melvin, R. G., Youngson, N. A., Garvin, M. R., Hu, Y., Nielsen, S., Thomas, T., Pickford, R., Bustamante, S., Vila-Sanjurjo, A., Smyth, G. K. & Ballard, J. W. O. (2018). Genotype to phenotype: Diet-by-mitochondrial DNA haplotype interactions drive metabolic flexibility and organismal fitness. PLOS GENETICS, 14 (11), https://doi.org/10.1371/journal.pgen.1007735.
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/11343/253350
dc.description.abstractDiet may be modified seasonally or by biogeographic, demographic or cultural shifts. It can differentially influence mitochondrial bioenergetics, retrograde signalling to the nuclear genome, and anterograde signalling to mitochondria. All these interactions have the potential to alter the frequencies of mtDNA haplotypes (mitotypes) in nature and may impact human health. In a model laboratory system, we fed four diets varying in Protein: Carbohydrate (P:C) ratio (1:2, 1:4, 1:8 and 1:16 P:C) to four homoplasmic Drosophila melanogaster mitotypes (nuclear genome standardised) and assayed their frequency in population cages. When fed a high protein 1:2 P:C diet, the frequency of flies harbouring Alstonville mtDNA increased. In contrast, when fed the high carbohydrate 1:16 P:C food the incidence of flies harbouring Dahomey mtDNA increased. This result, driven by differences in larval development, was generalisable to the replacement of the laboratory diet with fruits having high and low P:C ratios, perturbation of the nuclear genome and changes to the microbiome. Structural modelling and cellular assays suggested a V161L mutation in the ND4 subunit of complex I of Dahomey mtDNA was mildly deleterious, reduced mitochondrial functions, increased oxidative stress and resulted in an increase in larval development time on the 1:2 P:C diet. The 1:16 P:C diet triggered a cascade of changes in both mitotypes. In Dahomey larvae, increased feeding fuelled increased β-oxidation and the partial bypass of the complex I mutation. Conversely, Alstonville larvae upregulated genes involved with oxidative phosphorylation, increased glycogen metabolism and they were more physically active. We hypothesise that the increased physical activity diverted energy from growth and cell division and thereby slowed development. These data further question the use of mtDNA as an assumed neutral marker in evolutionary and population genetic studies. Moreover, if humans respond similarly, we posit that individuals with specific mtDNA variations may differentially metabolise carbohydrates, which has implications for a variety of diseases including cardiovascular disease, obesity, and perhaps Parkinson's Disease.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleGenotype to phenotype: Diet-by-mitochondrial DNA haplotype interactions drive metabolic flexibility and organismal fitness
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pgen.1007735
melbourne.affiliation.departmentSchool of Mathematics and Statistics
melbourne.source.titlePLoS Genetics
melbourne.source.volume14
melbourne.source.issue11
dc.rights.licenseCC BY
melbourne.elementsid1355722
melbourne.contributor.authorSmyth, Gordon
dc.identifier.eissn1553-7404
melbourne.accessrightsOpen Access


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