Edel M. Hyland
Adaptive Evolution in TRIF Leads to Discordance between Human and Mouse Innate Immune Signaling
Hyland, Edel M.; Webb, Andrew E.; Kennedy, Kathy F.; Gerek Ince, Z. Nevin; Loscher, Christine E.; O'Connell, Mary J.
Authors
Andrew E. Webb
Kathy F. Kennedy
Z. Nevin Gerek Ince
Christine E. Loscher
Professor and Chair of Molecular Evolution MARY O'CONNELL MARY.O'CONNELL@NOTTINGHAM.AC.UK
Professor of Molecular Evolution
Contributors
Andrea Betancourt
Editor
Abstract
The TIR domain-containing adapter inducing IFN-β (TRIF) protein is an innate immune system protein that mediates the MyD88-independent toll-like receptor response pathway in mice and humans. Previously, we identified positive selection at seven distinct residues in mouse TRIF (mTRIF), as compared with human and other mammalian orthologs, thus predicting protein functional shift in mTRIF. We reconstructed TRIF for the most recent common ancestor of mouse and human, and mutated this at the seven sites to their extant mouse/human states. We overexpressed these TRIF mutants in immortalized human and mouse cell lines and monitored TRIF-dependent cytokine production and gene expression induction. We show that optimal TRIF function in human and mouse is dependent on the identity of the positively selected sites. These data provide us with molecular data relating observed differences in response between mouse and human MyD88-independent signaling in the innate immune system with protein functional change.
Citation
Hyland, E. M., Webb, A. E., Kennedy, K. F., Gerek Ince, Z. N., Loscher, C. E., & O'Connell, M. J. (2021). Adaptive Evolution in TRIF Leads to Discordance between Human and Mouse Innate Immune Signaling. Genome Biology and Evolution, 13(12), Article evab268. https://doi.org/10.1093/gbe/evab268
Journal Article Type | Article |
---|---|
Acceptance Date | Nov 24, 2021 |
Online Publication Date | Dec 6, 2021 |
Publication Date | Dec 1, 2021 |
Deposit Date | Feb 9, 2022 |
Publicly Available Date | Feb 10, 2022 |
Journal | Genome Biology and Evolution |
Electronic ISSN | 1759-6653 |
Publisher | Oxford University Press |
Peer Reviewed | Peer Reviewed |
Volume | 13 |
Issue | 12 |
Article Number | evab268 |
DOI | https://doi.org/10.1093/gbe/evab268 |
Keywords | Genetics; Ecology, Evolution, Behavior and Systematics |
Public URL | https://nottingham-repository.worktribe.com/output/7345884 |
Publisher URL | https://academic.oup.com/gbe/article/13/12/evab268/6454097 |
Files
evab268
(687 Kb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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