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The article discusses the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain, which exhibits polarized prevalence in Southeast Asian populations. This variant enhances immune resilience against various pathogens and viper toxins in mice, and studies show it increases pathogen-specific IgG1+ memory B cell activation and antibody production. The findings suggest that this variant, potentially arising on a Neanderthal haplotype background, plays a significant role in reinforcing IgG1 antibody responses against critical organisms, highlighting the connection between human evolution and immune adaptation.
Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations. We uncovered a 190-kb genomic linkage disequilibrium block peaked in close proximity to this variant, suggestive of potential Darwinian selection. This variant confers heightened immune resilience against various pathogens and viper toxins in mice. Mechanistic studies involving severe acute respiratory syndrome coronavirus 2 infection and vaccinated individuals reveal that this variant enhances pathogen-specific IgG1+ memory B cell activation and antibody production. This G396R variant may have arisen on a Neanderthal haplotype background. These findings underscore the importance of an IGHG1 variant in reinforcing IgG1 antibody responses against life-threatening organisms, unraveling the intricate interplay between human evolution and immune adaptation.
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