The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome
- Autores
- Kamm, Gretel Betiana; Pisciottano, Francisco; Kliger, Rafi; Franchini, Lucia Florencia
- Año de publicación
- 2013
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- To identify the evolutionary genetic novelties that contributed to shape human-specific traits such as the use of a complex language, long-term planning and exceptional learning abilities is one of the ultimate frontiers of modern biology. Evolutionary signatures of functional shifts could be detected by comparing noncoding regions that are highly conserved across mammals or primates and rapidly accumulated nucleotide substitutions only in the lineage leading to humans. As gene loci densely populated with human-accelerated elements (HAEs) are more likely to have contributed to human-specific novelties, we sought to identify the transcriptional units and genomic 1 Mb intervals of the entire human genome carrying the highest number of HAEs. To this end, we took advantage of four available data sets of human genomic accelerated regions obtained through different comparisons and algorithms and performed a meta-analysis of the combined data. We found that the brain developmental transcription factor neuronal PAS domain-containing protein 3 (NPAS3) contains the largest cluster of noncoding-accelerated regions in the human genome with up to 14 elements that are highly conserved in mammals, including primates, but carry human-specific nucleotide substitutions. We then tested the ability of the 14 HAEs identified at the NPAS3 locus to act as transcriptional regulatory sequences in a reporter expression assay performed in transgenic zebrafish. We found that 11 out of the 14 HAEs present in NPAS3 act as transcriptional enhancers during development, particularly within the nervous system. As NPAS3 is known to play a crucial role during mammalian brain development, our results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution.
Fil: Kamm, Gretel Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
Fil: Pisciottano, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
Fil: Kliger, Rafi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; Argentina
Fil: Franchini, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina - Materia
-
NPAS3
BRAIN
EVOLUTION
HUMANS
SCHIZOPHRENIA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/3997
Ver los metadatos del registro completo
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spelling |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human GenomeKamm, Gretel BetianaPisciottano, FranciscoKliger, RafiFranchini, Lucia FlorenciaNPAS3BRAINEVOLUTIONHUMANSSCHIZOPHRENIAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1To identify the evolutionary genetic novelties that contributed to shape human-specific traits such as the use of a complex language, long-term planning and exceptional learning abilities is one of the ultimate frontiers of modern biology. Evolutionary signatures of functional shifts could be detected by comparing noncoding regions that are highly conserved across mammals or primates and rapidly accumulated nucleotide substitutions only in the lineage leading to humans. As gene loci densely populated with human-accelerated elements (HAEs) are more likely to have contributed to human-specific novelties, we sought to identify the transcriptional units and genomic 1 Mb intervals of the entire human genome carrying the highest number of HAEs. To this end, we took advantage of four available data sets of human genomic accelerated regions obtained through different comparisons and algorithms and performed a meta-analysis of the combined data. We found that the brain developmental transcription factor neuronal PAS domain-containing protein 3 (NPAS3) contains the largest cluster of noncoding-accelerated regions in the human genome with up to 14 elements that are highly conserved in mammals, including primates, but carry human-specific nucleotide substitutions. We then tested the ability of the 14 HAEs identified at the NPAS3 locus to act as transcriptional regulatory sequences in a reporter expression assay performed in transgenic zebrafish. We found that 11 out of the 14 HAEs present in NPAS3 act as transcriptional enhancers during development, particularly within the nervous system. As NPAS3 is known to play a crucial role during mammalian brain development, our results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution.Fil: Kamm, Gretel Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Pisciottano, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Kliger, Rafi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; ArgentinaFil: Franchini, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaOxford University Press2013-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3997Kamm, Gretel Betiana; Pisciottano, Francisco; Kliger, Rafi; Franchini, Lucia Florencia; The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome; Oxford University Press; Molecular Biology and Evolution; 30; 5; 5-2013; 1088-11020737-4038enginfo:eu-repo/semantics/altIdentifier/url/http://mbe.oxfordjournals.org/content/30/5/1088.longinfo:eu-repo/semantics/altIdentifier/doi/10.1093%2Fmolbev%2Fmst023info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670734/info:eu-repo/semantics/altIdentifier/issn/0737-4038info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:41:21Zoai:ri.conicet.gov.ar:11336/3997instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:41:21.27CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome |
title |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome |
spellingShingle |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome Kamm, Gretel Betiana NPAS3 BRAIN EVOLUTION HUMANS SCHIZOPHRENIA |
title_short |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome |
title_full |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome |
title_fullStr |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome |
title_full_unstemmed |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome |
title_sort |
The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome |
dc.creator.none.fl_str_mv |
Kamm, Gretel Betiana Pisciottano, Francisco Kliger, Rafi Franchini, Lucia Florencia |
author |
Kamm, Gretel Betiana |
author_facet |
Kamm, Gretel Betiana Pisciottano, Francisco Kliger, Rafi Franchini, Lucia Florencia |
author_role |
author |
author2 |
Pisciottano, Francisco Kliger, Rafi Franchini, Lucia Florencia |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
NPAS3 BRAIN EVOLUTION HUMANS SCHIZOPHRENIA |
topic |
NPAS3 BRAIN EVOLUTION HUMANS SCHIZOPHRENIA |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
To identify the evolutionary genetic novelties that contributed to shape human-specific traits such as the use of a complex language, long-term planning and exceptional learning abilities is one of the ultimate frontiers of modern biology. Evolutionary signatures of functional shifts could be detected by comparing noncoding regions that are highly conserved across mammals or primates and rapidly accumulated nucleotide substitutions only in the lineage leading to humans. As gene loci densely populated with human-accelerated elements (HAEs) are more likely to have contributed to human-specific novelties, we sought to identify the transcriptional units and genomic 1 Mb intervals of the entire human genome carrying the highest number of HAEs. To this end, we took advantage of four available data sets of human genomic accelerated regions obtained through different comparisons and algorithms and performed a meta-analysis of the combined data. We found that the brain developmental transcription factor neuronal PAS domain-containing protein 3 (NPAS3) contains the largest cluster of noncoding-accelerated regions in the human genome with up to 14 elements that are highly conserved in mammals, including primates, but carry human-specific nucleotide substitutions. We then tested the ability of the 14 HAEs identified at the NPAS3 locus to act as transcriptional regulatory sequences in a reporter expression assay performed in transgenic zebrafish. We found that 11 out of the 14 HAEs present in NPAS3 act as transcriptional enhancers during development, particularly within the nervous system. As NPAS3 is known to play a crucial role during mammalian brain development, our results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution. Fil: Kamm, Gretel Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Pisciottano, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Kliger, Rafi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones En Ingeniería Genética y Biología Molecular; Argentina Fil: Franchini, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina |
description |
To identify the evolutionary genetic novelties that contributed to shape human-specific traits such as the use of a complex language, long-term planning and exceptional learning abilities is one of the ultimate frontiers of modern biology. Evolutionary signatures of functional shifts could be detected by comparing noncoding regions that are highly conserved across mammals or primates and rapidly accumulated nucleotide substitutions only in the lineage leading to humans. As gene loci densely populated with human-accelerated elements (HAEs) are more likely to have contributed to human-specific novelties, we sought to identify the transcriptional units and genomic 1 Mb intervals of the entire human genome carrying the highest number of HAEs. To this end, we took advantage of four available data sets of human genomic accelerated regions obtained through different comparisons and algorithms and performed a meta-analysis of the combined data. We found that the brain developmental transcription factor neuronal PAS domain-containing protein 3 (NPAS3) contains the largest cluster of noncoding-accelerated regions in the human genome with up to 14 elements that are highly conserved in mammals, including primates, but carry human-specific nucleotide substitutions. We then tested the ability of the 14 HAEs identified at the NPAS3 locus to act as transcriptional regulatory sequences in a reporter expression assay performed in transgenic zebrafish. We found that 11 out of the 14 HAEs present in NPAS3 act as transcriptional enhancers during development, particularly within the nervous system. As NPAS3 is known to play a crucial role during mammalian brain development, our results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-05 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/3997 Kamm, Gretel Betiana; Pisciottano, Francisco; Kliger, Rafi; Franchini, Lucia Florencia; The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome; Oxford University Press; Molecular Biology and Evolution; 30; 5; 5-2013; 1088-1102 0737-4038 |
url |
http://hdl.handle.net/11336/3997 |
identifier_str_mv |
Kamm, Gretel Betiana; Pisciottano, Francisco; Kliger, Rafi; Franchini, Lucia Florencia; The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome; Oxford University Press; Molecular Biology and Evolution; 30; 5; 5-2013; 1088-1102 0737-4038 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://mbe.oxfordjournals.org/content/30/5/1088.long info:eu-repo/semantics/altIdentifier/doi/10.1093%2Fmolbev%2Fmst023 info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670734/ info:eu-repo/semantics/altIdentifier/issn/0737-4038 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University Press |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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