NF-κB Transcription Factors: Their Distribution, Family Expansion, Structural Conservation, and Evolution in Animals

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Genomics

Background:

• The Nuclear Factor Kappa B (NF-κB) transcription factor family regulates key biological processes like inflammation and immunity.
• NF-κB proteins share a conserved Rel homology domain (RHD) with DNA binding (RHD-DBD) and dimerization (RHD-DD) subdomains.
• Limited information exists on NF-κB distribution, evolution, and structural conservation across animal species.

Purpose of the Study:

• To comprehensively analyze the distribution, evolution, and structural conservation of NF-κB family proteins in animals.
• To identify novel NF-κB protein structures and subdomain variations.
• To elucidate the evolutionary origins and diversification of NF-κB proteins and their role in innate immunity.

Main Methods:

• Bioinformatic analysis of NF-κB family proteins across diverse animal phyla.
• Comparative analysis of protein sizes, conserved domains (RHD), and subdomains (RHD-DBD, RHD-DD).
• Phylogenetic analysis to infer evolutionary relationships and divergence times.

Main Results:

• NF-κB proteins exhibit distinct distribution patterns and variations in size and domain/subdomain composition across animals.
• Novel NF-κB proteins with multiple RHD-DBD and RHD-DDs were identified, some resulting from subdomain duplication.
• The exclusive presence of RelA/p65 in vertebrates indicates innate immunity originated in fishes and co-evolved through vertebrate classes.
• Phylogenetic grouping of NF-κB proteins mirrors animal taxonomy, confirming structural conservation post-speciation.
• Evolutionary analysis suggests p50/p105 and c-Rel emerged earliest in arthropod ancestors, followed by RelB, RelA, and p52/p100.

Conclusions:

• NF-κB family proteins display significant evolutionary diversification in structure and distribution across the animal kingdom.
• The study provides novel insights into the evolution of NF-κB signaling and its fundamental role in vertebrate innate immunity.
• Structural conservation of NF-κB proteins correlates with animal phylogeny, highlighting conserved functions throughout evolution.