Tingting Hao

Introduction: Flavonoid metabolism innovation is critical for seed plants’ terrestrial adaptation. Three key 2-oxoglutarate-dependent dioxygenase (2ODD) families—F3H, ANS, FLS—underpin flavonoid biosynthesis, but their evolutionary diversification mechanisms remain unclear. Methods: Comprehensive analyses were performed across 238 seed plant genomes, including phylogenetic/collinearity analyses, conserved motif detection, duplication-type classification, selection pressure assessment, and Brassica napus promoter/expression profiling. Results: These families originated from a common ancestral gene (ancestor X) and diversified via multiple duplications (TRD/WGD as primary drivers). Their evolution aligns with the EAC model, with subfunctionalization resolving ancestral multifunctionality. Structural conservation and lineage-specific motif variations support functional differentiation, and purifying selection predominates. Discussion: Our findings clarify the molecular evolutionary mechanisms of flavonoid pathway diversification, providing novel insights into the origin of flavonol and anthocyanin biosynthesis in seed plants.

Background: The interleukin-10 (IL-10) signaling system, comprising ligands (IL-10s) and receptors (IL-10Rs), plays critical roles in immune regulation, inflammation resolution, and disease pathogenesis. “IL-10 signaling system” here refers to the immunomodulatory signaling system composed of ligands (IL-10s) and receptors (IL-10Rs), which belong to different Protein families in evolution, but achieve functional synergy through the conserved JAK-STAT pathway. Understanding their evolutionary and functional dynamics is essential for elucidating immune mechanisms and therapeutic targeting. Methods: Through phylogenetic reconstruction, homology analysis, and sequence alignment across >400 animal species, we traced the evolutionary trajectory and structural–functional diversification of IL-10s and IL-10Rs. Results and Conclusions: IL-10 signaling components emerged in early vertebrates, with IL-10Rs originating in cartilaginous fishes (~450 Mya) and IL-10s diversifying in bony fishes (~400 Mya). Functional divergence yielded immunosuppressive (IL-10), barrier-protective (IL-20 subfamily), and antiviral (type III IFN) subgroups. Structurally, conserved motifs (e.g., IL-10R1 GYXXQ, IL-22 N54-glycosylation) underpin receptor–ligand binding and JAK/STAT signaling. Evolutionarily invariant residues suggest candidate therapeutic epitopes. This study provides an evolutionary framework highlighting functional conservation and species-specific adaptation within IL-10 signaling, with implications for immunotherapy and animal breeding.

An important area of interest for therapeutic development is the IL-1 superfamily, a critical group of immune regulators with profound implications in a variety of disorders. This study clarifies the evolutionary patterns of IL-1 family members by thoroughly analyzing more than 400 animal species, demonstrating their ancient roots that extend back to the earliest vertebrates. Important results show that, although IL-1 ligands expanded significantly over the evolution of mammals, their corresponding receptors remained remarkably structurally conserved. Identifying both lineage-specific adaptations and evolutionarily conserved residues provides vital information for treatment design. These findings point to the possibility of two different therapeutic strategies: addressing species-specific variants may allow for more targeted interventions, whereas focusing on conserved motifs may result in broad-acting treatments. The study also identified less well-known species as useful models for comprehending early immune systems. In addition to advancing our knowledge of the function of the IL-1 family in autoimmune, inflammatory, and carcinogenic illnesses, this research lays the groundwork for the development of more potent targeted therapeutics by creating an evolutionary framework for the IL-1 family.