Promoter shape varies across populations and affects promoter evolution and expression noise

Animal promoters initiate transcription either at precise positions (narrow promoters) or dispersed regions (broad promoters), a distinction referred to as promoter shape. Although highly conserved, the functional properties of promoters with different shapes and the genetic basis of their evolution...

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Detalhes bibliográficos
Autores: Schor, Ignacio Esteban, Degner, Jacob F., Harnett, Dermot, Cannavò, Enrico, Casale, Francesco P., Shim, Heejung, Garfield, David A., Birney, Ewan, Stephens, Matthew, Stegle, Oliver, Furlong, Eileen E. M.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2017
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/65679
Acesso em linha:http://hdl.handle.net/11336/65679
Access Level:Acceso aberto
Palavra-chave:Quantitative Trait Loci
Regulatory Qtl
Eqtl
Embryonic Development
Genetic Variation
Expression Noise
Epistasis
Core Promoter
Transcriptional Start Site
Transcription
Genetic Robustness
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descrição
Resumo:Animal promoters initiate transcription either at precise positions (narrow promoters) or dispersed regions (broad promoters), a distinction referred to as promoter shape. Although highly conserved, the functional properties of promoters with different shapes and the genetic basis of their evolution remain unclear. Here we used natural genetic variation across a panel of 81 Drosophila lines to measure changes in transcriptional start site (TSS) usage, identifying thousands of genetic variants affecting transcript levels (strength) or the distribution of TSSs within a promoter (shape). Our results identify promoter shape as a molecular trait that can evolve independently of promoter strength. Broad promoters typically harbor shape-associated variants, with signatures of adaptive selection. Single-cell measurements demonstrate that variants modulating promoter shape often increase expression noise, whereas heteroallelic interactions with other promoter variants alleviate these effects. These results uncover new functional properties of natural promoters and suggest the minimization of expression noise as an important factor in promoter evolution.

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