Ancestry and evolution of a secretory pathway serpin

<p>Abstract</p> <p>Background</p> <p>The serpin (serine protease inhibitor) superfamily constitutes a class of functionally highly diverse proteins usually encompassing several dozens of paralogs in mammals. Though phylogenetic classification of vertebrate serpins into...

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Main Authors: Ragg Hermann, Kumar Abhishek
Format: Article
Language:English
Published: BMC 2008-09-01
Series:BMC Evolutionary Biology
Online Access:http://www.biomedcentral.com/1471-2148/8/250
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author Ragg Hermann
Kumar Abhishek
author_facet Ragg Hermann
Kumar Abhishek
author_sort Ragg Hermann
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The serpin (serine protease inhibitor) superfamily constitutes a class of functionally highly diverse proteins usually encompassing several dozens of paralogs in mammals. Though phylogenetic classification of vertebrate serpins into six groups based on gene organisation is well established, the evolutionary roots beyond the fish/tetrapod split are unresolved. The aim of this study was to elucidate the phylogenetic relationships of serpins involved in surveying the secretory pathway routes against uncontrolled proteolytic activity.</p> <p>Results</p> <p>Here, rare genomic characters are used to show that orthologs of neuroserpin, a prominent representative of vertebrate group 3 <it>serpin </it>genes, exist in early diverging deuterostomes and probably also in cnidarians, indicating that the origin of a mammalian serpin can be traced back far in the history of eumetazoans. A C-terminal address code assigning association with secretory pathway organelles is present in all neuroserpin orthologs, suggesting that supervision of cellular export/import routes by antiproteolytic serpins is an ancient trait, though subtle functional and compartmental specialisations have developed during their evolution. The results also suggest that massive changes in the exon-intron organisation of <it>serpin </it>genes have occurred along the lineage leading to vertebrate <it>neuroserpin</it>, in contrast with the immediately adjacent <it>PDCD10 </it>gene that is linked to its neighbour at least since divergence of echinoderms. The intron distribution pattern of closely adjacent and co-regulated genes thus may experience quite different fates during evolution of metazoans.</p> <p>Conclusion</p> <p>This study demonstrates that the analysis of microsynteny and other rare characters can provide insight into the intricate family history of metazoan serpins. Serpins with the capacity to defend the main cellular export/import routes against uncontrolled endogenous and/or foreign proteolytic activity represent an ancient trait in eukaryotes that has been maintained continuously in metazoans though subtle changes affecting function and subcellular location have evolved. It is shown that the intron distribution pattern of <it>neuroserpin </it>gene orthologs has undergone substantial rearrangements during metazoan evolution.</p>
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spelling doaj.art-b340a70a3fea47cdac71179e2e7448272022-12-21T20:07:26ZengBMCBMC Evolutionary Biology1471-21482008-09-018125010.1186/1471-2148-8-250Ancestry and evolution of a secretory pathway serpinRagg HermannKumar Abhishek<p>Abstract</p> <p>Background</p> <p>The serpin (serine protease inhibitor) superfamily constitutes a class of functionally highly diverse proteins usually encompassing several dozens of paralogs in mammals. Though phylogenetic classification of vertebrate serpins into six groups based on gene organisation is well established, the evolutionary roots beyond the fish/tetrapod split are unresolved. The aim of this study was to elucidate the phylogenetic relationships of serpins involved in surveying the secretory pathway routes against uncontrolled proteolytic activity.</p> <p>Results</p> <p>Here, rare genomic characters are used to show that orthologs of neuroserpin, a prominent representative of vertebrate group 3 <it>serpin </it>genes, exist in early diverging deuterostomes and probably also in cnidarians, indicating that the origin of a mammalian serpin can be traced back far in the history of eumetazoans. A C-terminal address code assigning association with secretory pathway organelles is present in all neuroserpin orthologs, suggesting that supervision of cellular export/import routes by antiproteolytic serpins is an ancient trait, though subtle functional and compartmental specialisations have developed during their evolution. The results also suggest that massive changes in the exon-intron organisation of <it>serpin </it>genes have occurred along the lineage leading to vertebrate <it>neuroserpin</it>, in contrast with the immediately adjacent <it>PDCD10 </it>gene that is linked to its neighbour at least since divergence of echinoderms. The intron distribution pattern of closely adjacent and co-regulated genes thus may experience quite different fates during evolution of metazoans.</p> <p>Conclusion</p> <p>This study demonstrates that the analysis of microsynteny and other rare characters can provide insight into the intricate family history of metazoan serpins. Serpins with the capacity to defend the main cellular export/import routes against uncontrolled endogenous and/or foreign proteolytic activity represent an ancient trait in eukaryotes that has been maintained continuously in metazoans though subtle changes affecting function and subcellular location have evolved. It is shown that the intron distribution pattern of <it>neuroserpin </it>gene orthologs has undergone substantial rearrangements during metazoan evolution.</p>http://www.biomedcentral.com/1471-2148/8/250
spellingShingle Ragg Hermann
Kumar Abhishek
Ancestry and evolution of a secretory pathway serpin
BMC Evolutionary Biology
title Ancestry and evolution of a secretory pathway serpin
title_full Ancestry and evolution of a secretory pathway serpin
title_fullStr Ancestry and evolution of a secretory pathway serpin
title_full_unstemmed Ancestry and evolution of a secretory pathway serpin
title_short Ancestry and evolution of a secretory pathway serpin
title_sort ancestry and evolution of a secretory pathway serpin
url http://www.biomedcentral.com/1471-2148/8/250
work_keys_str_mv AT ragghermann ancestryandevolutionofasecretorypathwayserpin
AT kumarabhishek ancestryandevolutionofasecretorypathwayserpin