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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.

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Authors

Edel M. Hyland

Andrew E. Webb

Kathy F. Kennedy

Z. Nevin Gerek Ince

Christine E. Loscher



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

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