Reference Report

Reference
Citation	Grönke, S., Clarke, D.F., Broughton, S., Andrews, T.D., Partridge, L. (2010). Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 6(2): e1000857. (Export to RIS)
FlyBase ID	FBrf0210097
Publication Type	Research paper
PubMed ID	20195512
PubMed Abstract	Multicellular animals match costly activities, such as growth and reproduction, to the environment through nutrient-sensing pathways. The insulin/IGF signaling (IIS) pathway plays key roles in growth, metabolism, stress resistance, reproduction, and longevity in diverse organisms including mammals. Invertebrate genomes often contain multiple genes encoding insulin-like ligands, including seven Drosophila insulin-like peptides (DILPs). We investigated the evolution, diversification, redundancy, and functions of the DILPs, combining evolutionary analysis, based on the completed genome sequences of 12 Drosophila species, and functional analysis, based on newly-generated knock-out mutations for all 7 dilp genes in D. melanogaster. Diversification of the 7 DILPs preceded diversification of Drosophila species, with stable gene diversification and family membership, suggesting stabilising selection for gene function. Gene knock-outs demonstrated both synergy and compensation of expression between different DILPs, notably with DILP3 required for normal expression of DILPs 2 and 5 in brain neurosecretory cells and expression of DILP6 in the fat body compensating for loss of brain DILPs. Loss of DILP2 increased lifespan and loss of DILP6 reduced growth, while loss of DILP7 did not affect fertility, contrary to its proposed role as a Drosophila relaxin. Importantly, loss of DILPs produced in the brain greatly extended lifespan but only in the presence of the endosymbiontic bacterium Wolbachia, demonstrating a specific interaction between IIS and Wolbachia in lifespan regulation. Furthermore, loss of brain DILPs blocked the responses of lifespan and fecundity to dietary restriction (DR) and the DR response of these mutants suggests that IIS extends lifespan through mechanisms that both overlap with those of DR and through additional mechanisms that are independent of those at work in DR. Evolutionary conservation has thus been accompanied by synergy, redundancy, and functional differentiation between DILPs, and these features may themselves be of evolutionary advantage.
DOI	10.1371/journal.pgen.1000857
Related Publication(s)
Personal communication to FlyBase	Ilp5[3] and Ilp5[4] alleles. Gronke, 2010.5.12, Ilp5[3] and Ilp5[4] alleles. [FBrf0211047]
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Secondary IDs
Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Genet.
Title	PLoS Genetics
Publication Year	2005-
ISBN/ISSN	1553-7404 1553-7390
Data from Reference
Aberrations (4)
	Df(1)Ilp6⁴¹ Df(1)Ilp6⁶⁸ Df(3L)Ilp1-4 Df(3L)Ilp2-3
Alleles (18)
	Ilp1¹ Ilp1^{w.Scer\SceI.RS} Ilp2¹ Ilp2^{w.Scer\SceI.RS} Ilp3¹ Ilp3^{w.Scer\SceI.RS} Ilp4¹ Ilp4^{w.Scer\SceI.RS} Ilp5¹ Ilp5^{w.Scer\SceI.RS} Ilp6⁴¹ Ilp7¹ Ilp7^{w.Scer\SceI.RS} phl⁴¹ phl⁶⁸ Scer\FLP1^hs.PP Scer\SCEI^hs.PR w^+mW.hs
Constructs (10)
	P{70FLP} P{70I-SceI} P{FRT(w^+mW.hs.Ilp1-4^Scer\SceI.RS)} P{FRT(w^+mW.hs.Ilp1^Scer\SceI.RS)} P{FRT(w^+mW.hs.Ilp2-3^Scer\SceI.RS)} P{FRT(w^+mW.hs.Ilp2^Scer\SceI.RS)} P{FRT(w^+mW.hs.Ilp3^Scer\SceI.RS)} P{FRT(w^+mW.hs.Ilp4^Scer\SceI.RS)} P{FRT(w^+mW.hs.Ilp5^Scer\SceI.RS)} P{FRT(w^+mW.hs.Ilp7^Scer\SceI.RS)}
Genes (18)
	CG2854 CG14050 CR33218 CR34052 Dgri\GH15432 Dgri\GH15434 Ilp1 Ilp2 Ilp3 Ilp4 Ilp5 Ilp6 Ilp7 ImpL2 phl Scer\FLP1 Scer\SCEI Thor
Insertions (1)
	P{SUPor-P}phl^KG04972
Natural transposons (1)
	P-element