Natural variation in sugar tolerance associates with changes in signaling and mitochondrial ribosome biogenesis
Abstract
How dietary selection impacts genome evolution to define the optimal range of nutrient intake is a poorly understood question with medical relevance. We have addressed this question by analyzing Drosophila simulans and sechellia, recently diverged species with differential diet choice. D. sechellia larvae, specialized to a nutrient scarce diet, did not survive on sugar rich conditions, while the generalist species D. simulans was sugar tolerant. Sugar tolerance in D. simulans was a tradeoff for performance on low energy diet and was associated with global reprogramming of metabolic gene expression. Hybridization and phenotype-based introgression revealed the genomic regions of D. simulans that were sufficient for sugar tolerance. These regions included genes that are involved in mitochondrial ribosome biogenesis and intracellular signaling, such as PPP1R15/Gadd34 and SERCA, which contributed to sugar tolerance. In conclusion, genomic variation affecting genes involved in global metabolic control defines the optimal range for dietary macronutrient composition.
Data availability
Genome sequencing and RNA sequencing datasets have bee placed into NCBI SRA archive, Study # SRP158000. A link is provided for reviewers in the Materials and Methods.
Article and author information
Author details
Funding
Suomen Akatemia (286767)
- Ville Hietakangas
Novo Nordisk Foundation (NNF16OC0021460)
- Ville Hietakangas
Sigrid Juséliuksen Säätiö
- Ville Hietakangas
Finnish Diabetes Foundation
- Ville Hietakangas
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Patricia J Wittkopp, University of Michigan, United States
Publication history
- Received: August 6, 2018
- Accepted: November 27, 2018
- Accepted Manuscript published: November 27, 2018 (version 1)
- Version of Record published: December 20, 2018 (version 2)
Copyright
© 2018, Melvin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Funding This work is supported by the National Research Foundation Singapore (NRF-NRFF2017-02), PRECISION Health Research, Singapore (PRECISE) and the Agency for Science, Technology and Research (A*STAR). WP Koh was supported by National Medical Research Council, Singapore (NMRC/CSA/0055/2013). CC Khor was supported by National Research Foundation Singapore (NRF-NRFI2018-01). Rajkumar Dorajoo received a grant from the Agency for Science, Technology and Research Career Development Award (A*STAR CDA - 202D8090), and from Ministry of Health Healthy Longevity Catalyst Award (HLCA20Jan-0022). The Singapore Chinese Health Study was supported by grants from the National Medical Research Council, Singapore (NMRC/CIRG/1456/2016) and the U.S. National Institutes of Health [NIH] (R01 CA144034 and UM1 CA182876).
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