Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/155832 |
Resumo: | In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life. Here, we analysed the evolution of CHD proteins by performing a comparative study of the functional domains of CHD proteins between orthologous and paralogous protein sequences. Our findings show that the highest degree of inter-species conservation was observed at Group II (CHD3, CHD4, and CHD5) and that most of the pathological variations documented in humans involve amino acid residues that are conserved not only between species but also between paralogs. The parallel analysis of both orthologous and paralogous proteins, in cases where gene duplications have occurred, provided extra information showing patterns of flexibility as well as interchangeability between amino acid positions. This added complexity needs to be considered when the impact of novel mutations is assessed in terms of evolutionary conservation. |
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Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteinsChromatin remod-ellingChromodomains helicase DNA-binding proteinEvolutionary conservationNeurodevelopmentTranscription regulationIn the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life. Here, we analysed the evolution of CHD proteins by performing a comparative study of the functional domains of CHD proteins between orthologous and paralogous protein sequences. Our findings show that the highest degree of inter-species conservation was observed at Group II (CHD3, CHD4, and CHD5) and that most of the pathological variations documented in humans involve amino acid residues that are conserved not only between species but also between paralogs. The parallel analysis of both orthologous and paralogous proteins, in cases where gene duplications have occurred, provided extra information showing patterns of flexibility as well as interchangeability between amino acid positions. This added complexity needs to be considered when the impact of novel mutations is assessed in terms of evolutionary conservation.MDPI20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/155832eng2073-442510.3390/genes12111827Cardoso, ARLopes-Marques, MOliveira, MAmorim, APrata, MJAzevedo, Linfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-22T01:35:45Zoai:repositorio-aberto.up.pt:10216/155832Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:54:32.062419Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins |
title |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins |
spellingShingle |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins Cardoso, AR Chromatin remod-elling Chromodomains helicase DNA-binding protein Evolutionary conservation Neurodevelopment Transcription regulation |
title_short |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins |
title_full |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins |
title_fullStr |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins |
title_full_unstemmed |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins |
title_sort |
Genetic variability of the functional domains of chromodomains helicase DNA-binding (CHD) proteins |
author |
Cardoso, AR |
author_facet |
Cardoso, AR Lopes-Marques, M Oliveira, M Amorim, A Prata, MJ Azevedo, L |
author_role |
author |
author2 |
Lopes-Marques, M Oliveira, M Amorim, A Prata, MJ Azevedo, L |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Cardoso, AR Lopes-Marques, M Oliveira, M Amorim, A Prata, MJ Azevedo, L |
dc.subject.por.fl_str_mv |
Chromatin remod-elling Chromodomains helicase DNA-binding protein Evolutionary conservation Neurodevelopment Transcription regulation |
topic |
Chromatin remod-elling Chromodomains helicase DNA-binding protein Evolutionary conservation Neurodevelopment Transcription regulation |
description |
In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life. Here, we analysed the evolution of CHD proteins by performing a comparative study of the functional domains of CHD proteins between orthologous and paralogous protein sequences. Our findings show that the highest degree of inter-species conservation was observed at Group II (CHD3, CHD4, and CHD5) and that most of the pathological variations documented in humans involve amino acid residues that are conserved not only between species but also between paralogs. The parallel analysis of both orthologous and paralogous proteins, in cases where gene duplications have occurred, provided extra information showing patterns of flexibility as well as interchangeability between amino acid positions. This added complexity needs to be considered when the impact of novel mutations is assessed in terms of evolutionary conservation. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 2021-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/155832 |
url |
https://hdl.handle.net/10216/155832 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2073-4425 10.3390/genes12111827 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136433089282048 |