Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster

Hirokazu Okada, H. Alexander Ebhardt, Sibylle Chantal Vonesch, Ruedi Aebersold () and Ernst Hafen ()
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Hirokazu Okada: Institute of Molecular Systems Biology, ETH Zurich
H. Alexander Ebhardt: Institute of Molecular Systems Biology, ETH Zurich
Sibylle Chantal Vonesch: Institute of Molecular Systems Biology, ETH Zurich
Ruedi Aebersold: Institute of Molecular Systems Biology, ETH Zurich
Ernst Hafen: Institute of Molecular Systems Biology, ETH Zurich

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype–phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.

Date: 2016
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DOI: 10.1038/ncomms12649

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