Natural selection directing molecular evolution in vertebrate viral sensors

Area of Science:

• Evolutionary biology
• Immunology
• Molecular biology

Background:

• Pathogen-driven diseases induce molecular adaptations in host immunity.
• Viral infections can stimulate positive selection, diversifying host receptors that recognize them.
• The evolutionary modes of distinct animal virus-sensing systems remain largely uncharacterized.

Approach:

• This review comparatively analyzes natural selection impacting the molecular evolution of vertebrate viral-binding pattern recognition receptors (PRRs).
• Evidence for diversifying selection was examined in Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and oligoadenylate synthetases (OASs).
• The study also considered other PRR families, including AIM2-like receptors, C-type lectin receptors (CLRs), and cyclic GMP-AMP synthetase, where molecular evolution studies are scarce.

Key Points:

• Despite prevalent negative selection due to functional constraints, multiple lines of evidence indicate diversifying selection in TLRs, NLRs, RLRs, and OASs.
• Positively selected sites are often located in ligand-binding regions, suggesting impacts on viral detection, though experimental validation is limited.
• Comparative insights into the molecular evolution of PRR families like AIM2-like receptors, CLRs, and cyclic GMP-AMP synthetase are hindered by a lack of studies.

Conclusions:

• Shared characteristics in the evolution of viral sensors across vertebrates are identified.
• Priorities for future research are highlighted to advance understanding of immune receptor evolution and function.
• Further investigation is needed to experimentally confirm the functional impact of identified selection sites on viral detection.