{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["McGrath JJC"],"funding":["National Institute of Allergy and Infectious Diseases","Bill & Melinda Gates Foundation","Centers for Disease Control and Prevention","National Institute of Allergy and Infectious Diseases Division of Intramural Research","NIAID NIH HHS","National Institutes of Health","Gates Foundation","Canadian Institutes of Health Research","Leukemia and Lymphoma Society"],"pagination":["430-444.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12063209"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["85(2)"],"pubmed_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"],"journal":["Molecular cell"],"pubmed_title":["Mutability and hypermutation antagonize immunoglobulin codon optimality."],"pmcid":["PMC12063209"],"funding_grant_id":["P01AI165077","75N93019C00051","LLS 7027-23","U01 AI144616","U19 AI168632","U01AI153700","5U01AI144616","1U19AI168632","INV-004956","75D30119C06088","U01 AI165452","75N93021C00014","P01 AI165077","LLS-SCOR 7026-21","U01 AI153700","75N93019R00028","1U01AI165452"],"pubmed_authors":["Changrob S","Park J","Chervin JC","Huang M","Fu Y","Nelson SA","Li L","Wilson PC","Zheng NY","Wilbanks GD","Georgiou G","Kent JR","Inghirami G","Troxell CA","Madariaga MLL","McGrath JJC","Sun J"],"additional_accession":[]},"is_claimable":false,"name":"Mutability and hypermutation antagonize immunoglobulin codon optimality.","description":"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","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-07-15T06:06:36.074Z","creation":"2026-07-01T03:07:33.996Z"},"accession":"S-EPMC12063209","cross_references":{"pubmed":["39708804"],"doi":["10.1016/j.molcel.2024.11.033"]}}