Genetic variation of macronutrient tolerance in Drosophila melanogaster

Havula, E.;Ghazanfar, S.;Lamichane, N.;Francis, D.;Hasygar, K.;Liu, Y.;Alton, L.A.;Johnstone, J.;Needham, E.J.;Pulpitel, T.;Clark, T.;Niranjan, H.N.;Shang, V.;Tong, V.;Jiwnani, N.;Audia, G.;Alves, A.N.;Sylow, L.;Mirth, C.;Neely, G.G.;Yang, J.;Hietakangas, V.;Simpson, S.J.;Senior, A.M.

Dena Francis

Abstract

Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster, often considered a "dietary generalist", displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8, Pkn and Eip75B. We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailless, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.

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Nature Communications

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2041-1723

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Nature Publishing Group

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DOI

10.1038/s41467-022-29183-x