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Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes

BACKGROUND: The cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. Although they have been the subject of many studies, little is known about their genesis, evolution and functional diversification. Our aim has been to obtain...

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Autores principales: Kordiš, Dušan, Turk, Vito
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784779/
https://www.ncbi.nlm.nih.gov/pubmed/19919722
http://dx.doi.org/10.1186/1471-2148-9-266
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author Kordiš, Dušan
Turk, Vito
author_facet Kordiš, Dušan
Turk, Vito
author_sort Kordiš, Dušan
collection PubMed
description BACKGROUND: The cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. Although they have been the subject of many studies, little is known about their genesis, evolution and functional diversification. Our aim has been to obtain a comprehensive insight into their origin, distribution, diversity, evolution and classification in Eukaryota, Bacteria and Archaea. RESULTS: We have identified in silico the full complement of the cystatin superfamily in more than 2100 prokaryotic and eukaryotic genomes. The analysis of numerous eukaryotic genomes has provided strong evidence for the emergence of this superfamily in the ancestor of eukaryotes. The progenitor of this superfamily was most probably intracellular and lacked a signal peptide and disulfide bridges, much like the extant Giardia cystatin. A primordial gene duplication produced two ancestral eukaryotic lineages, cystatins and stefins. While stefins remain encoded by a single or a small number of genes throughout the eukaryotes, the cystatins have undergone a more complex and dynamic evolution through numerous gene and domain duplications. In the cystatin superfamily we discovered twenty vertebrate-specific and three angiosperm-specific orthologous families, indicating that functional diversification has occurred only in multicellular eukaryotes. In vertebrate orthologous families, the prevailing trends were loss of the ancestral inhibitory activity and acquisition of novel functions in innate immunity. Bacterial cystatins and stefins may be emergency inhibitors that enable survival of bacteria in the host, defending them from the host's proteolytic activity. CONCLUSION: This study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification. The findings of this comprehensive study provide guides for future structural and evolutionary studies of the cystatin superfamily as well as of other protease inhibitors and proteases.
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spelling pubmed-27847792009-11-28 Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes Kordiš, Dušan Turk, Vito BMC Evol Biol Research article BACKGROUND: The cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. Although they have been the subject of many studies, little is known about their genesis, evolution and functional diversification. Our aim has been to obtain a comprehensive insight into their origin, distribution, diversity, evolution and classification in Eukaryota, Bacteria and Archaea. RESULTS: We have identified in silico the full complement of the cystatin superfamily in more than 2100 prokaryotic and eukaryotic genomes. The analysis of numerous eukaryotic genomes has provided strong evidence for the emergence of this superfamily in the ancestor of eukaryotes. The progenitor of this superfamily was most probably intracellular and lacked a signal peptide and disulfide bridges, much like the extant Giardia cystatin. A primordial gene duplication produced two ancestral eukaryotic lineages, cystatins and stefins. While stefins remain encoded by a single or a small number of genes throughout the eukaryotes, the cystatins have undergone a more complex and dynamic evolution through numerous gene and domain duplications. In the cystatin superfamily we discovered twenty vertebrate-specific and three angiosperm-specific orthologous families, indicating that functional diversification has occurred only in multicellular eukaryotes. In vertebrate orthologous families, the prevailing trends were loss of the ancestral inhibitory activity and acquisition of novel functions in innate immunity. Bacterial cystatins and stefins may be emergency inhibitors that enable survival of bacteria in the host, defending them from the host's proteolytic activity. CONCLUSION: This study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification. The findings of this comprehensive study provide guides for future structural and evolutionary studies of the cystatin superfamily as well as of other protease inhibitors and proteases. BioMed Central 2009-11-18 /pmc/articles/PMC2784779/ /pubmed/19919722 http://dx.doi.org/10.1186/1471-2148-9-266 Text en Copyright ©2009 Kordiš and Turk; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research article
Kordiš, Dušan
Turk, Vito
Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
title Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
title_full Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
title_fullStr Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
title_full_unstemmed Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
title_short Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
title_sort phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784779/
https://www.ncbi.nlm.nih.gov/pubmed/19919722
http://dx.doi.org/10.1186/1471-2148-9-266
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