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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| Autores principales: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/adae4be633d8474f9112743fb8ad7896 |
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| Sumario: | 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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