Adaptive radiation and structural tailoring of the Vietnamese Blec2 immunogenetic reservoir

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.

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.

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).

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.