Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan

Symonenko, Alexander V.; Roshina, Natalia V.; Rybina, Olga Y.; Tsybul’ko, Evgeniya A.; Krementsova, Anna V.; Mikhaleva, Elena A.; Alatortsev, Vladimir E.; Mukha, Dmitry V.; Pasyukova, Elena G.

doi:10.3390/ijms27188343

Open AccessArticle

Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan

by

Alexander V. Symonenko

^1,*

,

Natalia V. Roshina

^1,2,

Olga Y. Rybina

¹,

Evgeniya A. Tsybul’ko

¹,

Anna V. Krementsova

^1,3

,

Elena A. Mikhaleva

¹

,

Vladimir E. Alatortsev

¹,

Dmitry V. Mukha

²

and

Elena G. Pasyukova

¹

National Research Centre “Kurchatov Institute”, 2 Kurchatov Sq., 123182 Moscow, Russia

²

Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Str., 119991 Moscow, Russia

³

Emmanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygin St., 119334 Moscow, Russia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(18), 8343; https://doi.org/10.3390/ijms27188343 (registering DOI)

Submission received: 21 August 2026 / Revised: 12 September 2026 / Accepted: 14 September 2026 / Published: 19 September 2026

(This article belongs to the Special Issue Bioinformatics of Genome Regulation and Structure–2026)

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Abstract

Revealing gene expression patterns is essential for comprehending the genetic control of complex traits like lifespan. Analyzing structural variation in gene regulatory regions within natural populations is a promising approach in functional genetics, allowing us to identify regulatory sites that influence transcription and phenotype in vivo. We describe the structural variability of the 5′ regulatory region of the shuttle craft (stc) gene in the Alexandrov population (Russia) of Drosophila melanogaster, encoding a transcription factor homologous to human NF-X1. We evaluated the association of frequently occurring polymorphisms with fly lifespan from inbred lines sampled in 2010, 2011, and 2014. Two polymorphisms in the stc 5′ regulatory region exhibit strong associations with both lifespan and embryonic stc transcript levels. Their role in expression regulation was evaluated via reporter gene assays conducted in S2 Drosophila cell culture. The ‘C’ allele at one polymorphic site and ‘T’ at the other are associated with increased longevity and decreased embryonic stc transcription, reaffirming the link between gene expression and lifespan we previously established. Furthermore, comparing stc 5′ regulatory region variability across Alexandrov, European and African populations suggests that the macro-geographic distribution of these longevity-associated variants is consistent with a potential role in latitudinal or climatic adaptation.

Keywords: lifespan; transcription; transcription factors; natural populations; polymorphism; SNP; cold tolerance; Drosophila melanogaster

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MDPI and ACS Style

Symonenko, A.V.; Roshina, N.V.; Rybina, O.Y.; Tsybul’ko, E.A.; Krementsova, A.V.; Mikhaleva, E.A.; Alatortsev, V.E.; Mukha, D.V.; Pasyukova, E.G. Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan. Int. J. Mol. Sci. 2026, 27, 8343. https://doi.org/10.3390/ijms27188343

AMA Style

Symonenko AV, Roshina NV, Rybina OY, Tsybul’ko EA, Krementsova AV, Mikhaleva EA, Alatortsev VE, Mukha DV, Pasyukova EG. Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan. International Journal of Molecular Sciences. 2026; 27(18):8343. https://doi.org/10.3390/ijms27188343

Chicago/Turabian Style

Symonenko, Alexander V., Natalia V. Roshina, Olga Y. Rybina, Evgeniya A. Tsybul’ko, Anna V. Krementsova, Elena A. Mikhaleva, Vladimir E. Alatortsev, Dmitry V. Mukha, and Elena G. Pasyukova. 2026. "Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan" International Journal of Molecular Sciences 27, no. 18: 8343. https://doi.org/10.3390/ijms27188343

APA Style

Symonenko, A. V., Roshina, N. V., Rybina, O. Y., Tsybul’ko, E. A., Krementsova, A. V., Mikhaleva, E. A., Alatortsev, V. E., Mukha, D. V., & Pasyukova, E. G. (2026). Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan. International Journal of Molecular Sciences, 27(18), 8343. https://doi.org/10.3390/ijms27188343

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Naturally Occurring Variability in the Regulatory Region of the Drosophila melanogaster Gene shuttle craft Affects Gene Expression and Lifespan

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