AUTHOR=Martinez-Barnetche Jesús , Godoy-Lozano Elizabeth Ernestina , Saint Remy-Hernández Stephanie , Pacheco-Olvera Diana Laura , Téllez-Sosa Juan , Valdovinos-Torres Humberto , Pastelin-Palacios Rodolfo , Mena Horacio , Zambrano Luis , López-Macías Constantino 

TITLE=Characterization of immunoglobulin loci in the gigantic genome of Ambystoma mexicanum

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1039274

DOI=10.3389/fimmu.2023.1039274

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>The axolotl, <italic>Ambystoma mexicanum</italic> is a unique biological model for complete tissue regeneration. Is a neotenic endangered species and is highly susceptible to environmental stress, including infectious disease. In contrast to other amphibians, the axolotl is particularly vulnerable to certain viral infections. Like other salamanders, the axolotl genome is one of the largest (32 Gb) and the impact of genome size on Ig <italic>loci</italic> architecture is unknown. To better understand the immune response in axolotl, we aimed to characterize the immunoglobulin <italic>loci</italic> of <italic>A. mexicanum</italic> and compare it with other model vertebrates.</p></sec><sec><title>Methods</title><p>The most recently published genome sequence of <italic>A. mexicanum</italic> (V6) was used for alignment-based annotation and manual curation using previously described axolotl Ig sequences or reference sequences from other vertebrates. Gene models were further curated using <italic>A. mexicanum</italic> spleen RNA-seq data. Human, <italic>Xenopus tropicalis</italic>, <italic>Danio rerio</italic> (zebrafish), and eight tetrapod reference genomes were used for comparison.</p></sec><sec><title>Results</title><p>Canonical <italic>A. mexicanum</italic> heavy chain (IGH), lambda (IGL), sigma (IGS), and the putative surrogate light chain (SLC) <italic>loci</italic> were identified. No kappa <italic>locus</italic> was found. More than half of the IGHV genes and the IGHF gene are pseudogenes and there is no clan I IGHV genes. Although the IGH <italic>locus</italic> size is proportional to genome size, we found local size restriction in the IGHM gene and the V gene intergenic distances. In addition, there were V genes with abnormally large V-intron sizes, which correlated with loss of gene functionality.</p></sec><sec><title>Conclusion</title><p>The <italic>A. mexicanum</italic> immunoglobulin <italic>loci</italic> share the same general genome architecture as most studied tetrapods. Consistent with its large genome, Ig <italic>loci</italic> are larger; however, local size restrictions indicate evolutionary constraints likely to be imposed by high transcriptional demand of certain Ig genes, as well as the V(D)J recombination over very long genomic distance ranges. The <italic>A. mexicanum</italic> has undergone an extensive process of Ig gene loss which partially explains a reduced potential repertoire diversity that may contribute to its impaired antibody response.</p></sec>