Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective

Two key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ulti...

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Main Authors: Veronika Krchlíková, Tomáš Hron, Martin Těšický, Tao Li, Jiří Hejnar, Michal Vinkler, Daniel Elleder
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/11/2131
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author Veronika Krchlíková
Tomáš Hron
Martin Těšický
Tao Li
Jiří Hejnar
Michal Vinkler
Daniel Elleder
author_facet Veronika Krchlíková
Tomáš Hron
Martin Těšický
Tao Li
Jiří Hejnar
Michal Vinkler
Daniel Elleder
author_sort Veronika Krchlíková
collection DOAJ
description Two key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ultimately activates interferon-stimulated genes (ISGs). While in rare cases <i>RIG-I</i> gene loss has been detected in mammalian and avian species, most notably in the chicken, <i>MDA5</i> pseudogenization has only been detected once in mammals. We have screened over a hundred publicly available avian genome sequences and describe an independent disruption of <i>MDA5</i> in two unrelated avian lineages, the storks (Ciconiiformes) and the rallids (Gruiformes). The results of our RELAX analysis confirmed the absence of negative selection in the <i>MDA5</i> pseudogene. In contrast to our prediction, we have shown, using multiple dN/dS-based approaches, that the <i>MDA5</i> loss does not appear to have resulted in any compensatory evolution in the <i>RIG-I</i> gene, which may partially share its ligand-binding specificity. Together, our results indicate that the <i>MDA5</i> pseudogenization may have important functional effects on immune responsiveness in these two avian clades.
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spelling doaj.art-adae4be633d8474f9112743fb8ad78962023-11-23T01:55:21ZengMDPI AGViruses1999-49152021-10-011311213110.3390/v13112131Repeated MDA5 Gene Loss in Birds: An Evolutionary PerspectiveVeronika Krchlíková0Tomáš Hron1Martin Těšický2Tao Li3Jiří Hejnar4Michal Vinkler5Daniel Elleder6Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech RepublicInstitute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Zoology, Faculty of Science, Charles University, 12843 Prague, Czech RepublicDepartment of Zoology, Faculty of Science, Charles University, 12843 Prague, Czech RepublicInstitute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech RepublicDepartment of Zoology, Faculty of Science, Charles University, 12843 Prague, Czech RepublicInstitute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech RepublicTwo key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ultimately activates interferon-stimulated genes (ISGs). While in rare cases <i>RIG-I</i> gene loss has been detected in mammalian and avian species, most notably in the chicken, <i>MDA5</i> pseudogenization has only been detected once in mammals. We have screened over a hundred publicly available avian genome sequences and describe an independent disruption of <i>MDA5</i> in two unrelated avian lineages, the storks (Ciconiiformes) and the rallids (Gruiformes). The results of our RELAX analysis confirmed the absence of negative selection in the <i>MDA5</i> pseudogene. In contrast to our prediction, we have shown, using multiple dN/dS-based approaches, that the <i>MDA5</i> loss does not appear to have resulted in any compensatory evolution in the <i>RIG-I</i> gene, which may partially share its ligand-binding specificity. Together, our results indicate that the <i>MDA5</i> pseudogenization may have important functional effects on immune responsiveness in these two avian clades.https://www.mdpi.com/1999-4915/13/11/2131avian genomeviral sensorsinnate immunitygene loss
spellingShingle Veronika Krchlíková
Tomáš Hron
Martin Těšický
Tao Li
Jiří Hejnar
Michal Vinkler
Daniel Elleder
Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective
Viruses
avian genome
viral sensors
innate immunity
gene loss
title Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective
title_full Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective
title_fullStr Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective
title_full_unstemmed Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective
title_short Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective
title_sort repeated mda5 gene loss in birds an evolutionary perspective
topic avian genome
viral sensors
innate immunity
gene loss
url https://www.mdpi.com/1999-4915/13/11/2131
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