Cargando…

The frequent evolutionary birth and death of functional promoters in mouse and human

Promoters are central to the regulation of gene expression. Changes in gene regulation are thought to underlie much of the adaptive diversification between species and phenotypic variation within populations. In contrast to earlier work emphasizing the importance of enhancer evolution and subtle seq...

Descripción completa

Detalles Bibliográficos
Autores principales: Young, Robert S., Hayashizaki, Yoshihide, Andersson, Robin, Sandelin, Albin, Kawaji, Hideya, Itoh, Masayoshi, Lassmann, Timo, Carninci, Piero, Bickmore, Wendy A., Forrest, Alistair R., Taylor, Martin S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579340/
https://www.ncbi.nlm.nih.gov/pubmed/26228054
http://dx.doi.org/10.1101/gr.190546.115
_version_ 1782391251700547584
author Young, Robert S.
Hayashizaki, Yoshihide
Andersson, Robin
Sandelin, Albin
Kawaji, Hideya
Itoh, Masayoshi
Lassmann, Timo
Carninci, Piero
Bickmore, Wendy A.
Forrest, Alistair R.
Taylor, Martin S.
author_facet Young, Robert S.
Hayashizaki, Yoshihide
Andersson, Robin
Sandelin, Albin
Kawaji, Hideya
Itoh, Masayoshi
Lassmann, Timo
Carninci, Piero
Bickmore, Wendy A.
Forrest, Alistair R.
Taylor, Martin S.
author_sort Young, Robert S.
collection PubMed
description Promoters are central to the regulation of gene expression. Changes in gene regulation are thought to underlie much of the adaptive diversification between species and phenotypic variation within populations. In contrast to earlier work emphasizing the importance of enhancer evolution and subtle sequence changes at promoters, we show that dramatic changes such as the complete gain and loss (collectively, turnover) of functional promoters are common. Using quantitative measures of transcription initiation in both humans and mice across 52 matched tissues, we discriminate promoter sequence gains from losses and resolve the lineage of changes. We also identify expression divergence and functional turnover between orthologous promoters, finding only the latter is associated with local sequence changes. Promoter turnover has occurred at the majority (>56%) of protein-coding genes since humans and mice diverged. Tissue-restricted promoters are the most evolutionarily volatile where retrotransposition is an important, but not the sole, source of innovation. There is considerable heterogeneity of turnover rates between promoters in different tissues, but the consistency of these in both lineages suggests that the same biological systems are similarly inclined to transcriptional rewiring. The genes affected by promoter turnover show evidence of adaptive evolution. In mice, promoters are primarily lost through deletion of the promoter containing sequence, whereas in humans, many promoters appear to be gradually decaying with weak transcriptional output and relaxed selective constraint. Our results suggest that promoter gain and loss is an important process in the evolutionary rewiring of gene regulation and may be a significant source of phenotypic diversification.
format Online
Article
Text
id pubmed-4579340
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-45793402015-10-01 The frequent evolutionary birth and death of functional promoters in mouse and human Young, Robert S. Hayashizaki, Yoshihide Andersson, Robin Sandelin, Albin Kawaji, Hideya Itoh, Masayoshi Lassmann, Timo Carninci, Piero Bickmore, Wendy A. Forrest, Alistair R. Taylor, Martin S. Genome Res Research Promoters are central to the regulation of gene expression. Changes in gene regulation are thought to underlie much of the adaptive diversification between species and phenotypic variation within populations. In contrast to earlier work emphasizing the importance of enhancer evolution and subtle sequence changes at promoters, we show that dramatic changes such as the complete gain and loss (collectively, turnover) of functional promoters are common. Using quantitative measures of transcription initiation in both humans and mice across 52 matched tissues, we discriminate promoter sequence gains from losses and resolve the lineage of changes. We also identify expression divergence and functional turnover between orthologous promoters, finding only the latter is associated with local sequence changes. Promoter turnover has occurred at the majority (>56%) of protein-coding genes since humans and mice diverged. Tissue-restricted promoters are the most evolutionarily volatile where retrotransposition is an important, but not the sole, source of innovation. There is considerable heterogeneity of turnover rates between promoters in different tissues, but the consistency of these in both lineages suggests that the same biological systems are similarly inclined to transcriptional rewiring. The genes affected by promoter turnover show evidence of adaptive evolution. In mice, promoters are primarily lost through deletion of the promoter containing sequence, whereas in humans, many promoters appear to be gradually decaying with weak transcriptional output and relaxed selective constraint. Our results suggest that promoter gain and loss is an important process in the evolutionary rewiring of gene regulation and may be a significant source of phenotypic diversification. Cold Spring Harbor Laboratory Press 2015-10 /pmc/articles/PMC4579340/ /pubmed/26228054 http://dx.doi.org/10.1101/gr.190546.115 Text en © 2015 Young et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research
Young, Robert S.
Hayashizaki, Yoshihide
Andersson, Robin
Sandelin, Albin
Kawaji, Hideya
Itoh, Masayoshi
Lassmann, Timo
Carninci, Piero
Bickmore, Wendy A.
Forrest, Alistair R.
Taylor, Martin S.
The frequent evolutionary birth and death of functional promoters in mouse and human
title The frequent evolutionary birth and death of functional promoters in mouse and human
title_full The frequent evolutionary birth and death of functional promoters in mouse and human
title_fullStr The frequent evolutionary birth and death of functional promoters in mouse and human
title_full_unstemmed The frequent evolutionary birth and death of functional promoters in mouse and human
title_short The frequent evolutionary birth and death of functional promoters in mouse and human
title_sort frequent evolutionary birth and death of functional promoters in mouse and human
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579340/
https://www.ncbi.nlm.nih.gov/pubmed/26228054
http://dx.doi.org/10.1101/gr.190546.115
work_keys_str_mv AT youngroberts thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT hayashizakiyoshihide thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT anderssonrobin thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT sandelinalbin thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT kawajihideya thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT itohmasayoshi thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT lassmanntimo thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT carnincipiero thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT bickmorewendya thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT forrestalistairr thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT taylormartins thefrequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT youngroberts frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT hayashizakiyoshihide frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT anderssonrobin frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT sandelinalbin frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT kawajihideya frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT itohmasayoshi frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT lassmanntimo frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT carnincipiero frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT bickmorewendya frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT forrestalistairr frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman
AT taylormartins frequentevolutionarybirthanddeathoffunctionalpromotersinmouseandhuman