Adaptive radiation and structural tailoring of the Vietnamese Blec2 immunogenetic reservoir

Background: The global poultry industry faces a critical sustainability crisis driven by climate change and escalating disease threats, necessitating the identification of novel genetic reservoirs for resilience. The Major Histocompatibility Complex (MHC)-linked Blec2 gene, a member of the Killer Cell Lectin-like Receptor (KLR) family, serves as a molecular sentinel regulating Natural Killer (NK) cell-mediated immunity; however, its diversity remains poorly characterized in Southeast Asian avian populations.

Methods: This study utilized Illumina short-read sequencing and AlphaFold 3 modeling to investigate Blec2 polymorphism across 15 Vietnamese populations that comprised 13 indigenous breeds and two ancestral Red Junglefowl (Gallus gallus) lineages.

Results: We identified 11 unique alleles, including the novel variant VN11, that establish the Vietnamese gene pool as a distinct reservoir of immune diversity. Notably, eight alleles were restricted to indigenous breeds, which exhibited a higher nucleotide diversity (π = 0.012) than their wild progenitors (π = 0.009), suggesting that localized diversification has been driven by breed-specific selective pressures. Evolutionary analysis revealed a dual mechanism: (1) intense global purifying selection (ω ≤ 0.035) preserving the receptor’s structural scaffold and (2) localized positive selection at codons 11 and 18 that is predicted in silico to influence the receptor’s binding affinity for the MHC Class I (BF2) ligand. The hypothesized functional relevance of this diversity is highlighted by the identification of alleles homologous to haplotypes previously associated with high resistance, such as Blec2*VN2 (linked to H5N1 and Marek’s disease resistance in prior studies) and Blec2*VN9 (associated with respiratory virus resilience).

Conclusion: By integrating population genomics with in silico structural biology, this study provides the foundational data proposing Blec2 as a candidate locus for future Marker-Assisted Selection (MAS) research. While experimental functional validation remains necessary, our findings establish a hypothesis-driven framework for investigating how genetic reservoirs might be leveraged to enhance avian immunocompetence and secure sustainable poultry production against emerging viral threats.