Mutability and hypermutation antagonize immunoglobulin codon optimality.

ABSTRACT: The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality. Germline variable genes (IGVs) exhibit diverse optimality that is inversely related to mutability. Hypermutation deoptimizes heavy-chain (IGH) VDJ repertoires within human tonsils, bone marrow, lymph nodes (including SARS-CoV-2-specific clones), blood (HIV-1-specific clones), mice, and zebrafish. Analyses of mutation-affected codons show that targ

SUBMITTER: McGrath JJC 

PROVIDER: S-EPMC12063209 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature