Pospelova Mariia, Voss Katalin, Zamyatin Anton, Watson Corey T, Koepfli Klaus-Peter, Bankevich Anton, Pennell Matt, Safonova Yana
Computer Science and Engineering Department, Pennsylvania State University, State College, PA, USA.
Department of Computational Biology, Cornell University, Ithaca, NY, USA.
Mol Biol Evol. 2025 Jun 23. doi: 10.1093/molbev/msaf152.
Adaptive immune responses are mediated by the production of adaptive immune receptors, antibodies and T-cell receptors, that bind antigens, thus causing their neutralization. Unlike other proteins, adaptive immune receptors are not fully encoded in the germline genome and result from a complex of somatic processes collectively called V(D)J recombination affecting germline immunoglobulin (IG) and T-cell receptor (TR) loci consisting of template genes. While various existing studies report extreme diversity of antibodies and T-cell receptors, little is known about the diversity of germline IG and TR loci. To overcome this gap, the first comparative analysis of full-length sequences of IG/TR loci across 46 mammalian species from 13 taxonomic orders was performed. First, germline genes counts were shown to correlate in IGH/IGL and TRA/TRB and anticorrelate in IGK/IGL, possibly indicating co-evolution between corresponding chains. Second, structures of IG/TR loci were analyzed, and it was shown that IG/TR loci formed by long arrays of high multiplicity repeats are more common for species that have experienced population bottlenecks. Finally, haplotypes of IG/TR loci with little or no sequence similarity within a species were found, suggesting that they may have a limited potential for homologous recombination. These results demonstrate that IG/TR loci are rapidly evolving genomic regions whose structural variation is shaped by the population history of the species and open new perspectives for immunogenomics studies.
适应性免疫反应是由适应性免疫受体、抗体和T细胞受体介导的，这些受体与抗原结合，从而使其失活。与其他蛋白质不同，适应性免疫受体并非完全由种系基因组编码，而是由一系列统称为V(D)J重组的体细胞过程产生的，这些过程影响由模板基因组成的种系免疫球蛋白(IG)和T细胞受体(TR)基因座。虽然现有各种研究报告了抗体和T细胞受体的极端多样性，但对于种系IG和TR基因座的多样性却知之甚少。为了填补这一空白，我们对来自13个分类目的46种哺乳动物的IG/TR基因座全长序列进行了首次比较分析。首先，种系基因计数显示在IGH/IGL和TRA/TRB中呈正相关，而在IGK/IGL中呈负相关，这可能表明相应链之间存在共同进化。其次，对IG/TR基因座的结构进行了分析，结果表明，由高重复倍数的长阵列形成的IG/TR基因座在经历过种群瓶颈的物种中更为常见。最后，在一个物种内发现了几乎没有或没有序列相似性的IG/TR基因座单倍型，这表明它们可能具有有限的同源重组潜力。这些结果表明，IG/TR基因座是快速进化的基因组区域，其结构变异受物种种群历史的影响，为免疫基因组学研究开辟了新的视角。
