Regulation of Drosophila Lifespan by bellwether Promoter Alleles

Abstract Longevity varies among individuals, but how natural genetic variation contributes to variation in lifespan is poorly understood. Drosophila melanogaster presents an advantageous model system to explore the genetic underpinnings of longevity, since its generation time is brief and both the g...

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Autores principales:	Júlia Frankenberg Garcia, Mary Anna Carbone, Trudy F. C. Mackay, Robert R. H. Anholt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/52e9ddcee5544de9abae501bc3332df7
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spelling	oai:doaj.org-article:52e9ddcee5544de9abae501bc3332df72021-12-02T12:30:27ZRegulation of Drosophila Lifespan by bellwether Promoter Alleles10.1038/s41598-017-04530-x2045-2322https://doaj.org/article/52e9ddcee5544de9abae501bc3332df72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04530-xhttps://doaj.org/toc/2045-2322Abstract Longevity varies among individuals, but how natural genetic variation contributes to variation in lifespan is poorly understood. Drosophila melanogaster presents an advantageous model system to explore the genetic underpinnings of longevity, since its generation time is brief and both the genetic background and rearing environment can be precisely controlled. The bellwether (blw) gene encodes the α subunit of mitochondrial ATP synthase. Since metabolic rate may influence lifespan, we investigated whether alternative haplotypes in the blw promoter affect lifespan when expressed in a co-isogenic background. We amplified 521 bp upstream promoter sequences containing alternative haplotypes and assessed promoter activity both in vitro and in vivo using a luciferase reporter system. The AG haplotype showed significantly greater expression of luciferase than the GT haplotype. We then overexpressed a blw cDNA construct driven by either the AG or GT haplotype promoter in transgenic flies and showed that the AG haplotype also results in greater blw cDNA expression and a significant decrease in lifespan relative to the GT promoter haplotype, in male flies only. Thus, our results show that naturally occurring regulatory variants of blw affect lifespan in a sex-specific manner.Júlia Frankenberg GarciaMary Anna CarboneTrudy F. C. MackayRobert R. H. AnholtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Júlia Frankenberg Garcia Mary Anna Carbone Trudy F. C. Mackay Robert R. H. Anholt Regulation of Drosophila Lifespan by bellwether Promoter Alleles
description	Abstract Longevity varies among individuals, but how natural genetic variation contributes to variation in lifespan is poorly understood. Drosophila melanogaster presents an advantageous model system to explore the genetic underpinnings of longevity, since its generation time is brief and both the genetic background and rearing environment can be precisely controlled. The bellwether (blw) gene encodes the α subunit of mitochondrial ATP synthase. Since metabolic rate may influence lifespan, we investigated whether alternative haplotypes in the blw promoter affect lifespan when expressed in a co-isogenic background. We amplified 521 bp upstream promoter sequences containing alternative haplotypes and assessed promoter activity both in vitro and in vivo using a luciferase reporter system. The AG haplotype showed significantly greater expression of luciferase than the GT haplotype. We then overexpressed a blw cDNA construct driven by either the AG or GT haplotype promoter in transgenic flies and showed that the AG haplotype also results in greater blw cDNA expression and a significant decrease in lifespan relative to the GT promoter haplotype, in male flies only. Thus, our results show that naturally occurring regulatory variants of blw affect lifespan in a sex-specific manner.
format	article
author	Júlia Frankenberg Garcia Mary Anna Carbone Trudy F. C. Mackay Robert R. H. Anholt
author_facet	Júlia Frankenberg Garcia Mary Anna Carbone Trudy F. C. Mackay Robert R. H. Anholt
author_sort	Júlia Frankenberg Garcia
title	Regulation of Drosophila Lifespan by bellwether Promoter Alleles
title_short	Regulation of Drosophila Lifespan by bellwether Promoter Alleles
title_full	Regulation of Drosophila Lifespan by bellwether Promoter Alleles
title_fullStr	Regulation of Drosophila Lifespan by bellwether Promoter Alleles
title_full_unstemmed	Regulation of Drosophila Lifespan by bellwether Promoter Alleles
title_sort	regulation of drosophila lifespan by bellwether promoter alleles
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/52e9ddcee5544de9abae501bc3332df7
work_keys_str_mv	AT juliafrankenberggarcia regulationofdrosophilalifespanbybellwetherpromoteralleles AT maryannacarbone regulationofdrosophilalifespanbybellwetherpromoteralleles AT trudyfcmackay regulationofdrosophilalifespanbybellwetherpromoteralleles AT robertrhanholt regulationofdrosophilalifespanbybellwetherpromoteralleles
_version_	1718394335935856640

Regulation of Drosophila Lifespan by bellwether Promoter Alleles

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