Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, Netherlands.
Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, Netherlands.
Front Immunol. 2023 Dec 11;14:1308316. doi: 10.3389/fimmu.2023.1308316. eCollection 2023.
The killer cell immunoglobulin-like receptors (KIR) play a pivotal role in modulating the NK cell responses, for instance, through interaction with major histocompatibility complex (MHC) class I molecules. Both gene systems map to different chromosomes but co-evolved during evolution. The human gene family is characterized by abundant allelic polymorphism and copy number variation. In contrast, our knowledge of the repertoire in chimpanzees is limited to 39 reported alleles, with no available population data. Only three genomic region configurations have been mapped, and seventeen additional ones were deduced by genotyping.
Previously, we documented that the chimpanzee MHC class I repertoire has been skewed due to an ancient selective sweep. To understand the depth of the sweep, we set out to determine the full-length transcriptome - in our MHC characterized pedigreed West African chimpanzee cohort - using SMRT sequencing (PacBio). In addition, the genomic organization of 14 haplotypes was characterized by applying a Cas9-mediated enrichment approach in concert with long-read sequencing by Oxford Nanopore Technologies.
In the cohort, we discovered 35 undescribed and 15 already recorded alleles, and a novel hybrid gene. Some transcripts are subject to evolutionary conserved alternative splicing events. A detailed insight on the region dynamics (location and order of genes) was obtained, however, only five new region configurations were detected. The population data allowed to investigate the distribution of the MHC-C1 and C2-epitope specificity of the inhibitory lineage III KIR repertoire, and appears to be skewed towards C2.
Although the region is known to evolve fast, as observed in other primate species, our overall conclusion is that the genomic architecture and repertoire in West African chimpanzees exhibit only limited to moderate levels of variation. Hence, the ancient selective sweep that affected the chimpanzee MHC class I region may also have impacted the system.
杀伤细胞免疫球蛋白样受体 (KIR) 在调节 NK 细胞反应方面发挥着关键作用，例如，通过与主要组织相容性复合体 (MHC) Ⅰ类分子相互作用。这两个基因系统都位于不同的染色体上，但在进化过程中共同进化。人类基因家族的特点是丰富的等位基因多态性和拷贝数变异。相比之下，我们对黑猩猩的基因库的了解仅限于已报道的 39 个等位基因，且没有可用的群体数据。仅已映射到三个基因组区域配置，并且通过基因分型推断出另外十七个。
此前，我们记录了黑猩猩 MHC Ⅰ类 repertoire 由于古老的选择而发生了偏倚。为了了解该选择的深度，我们着手使用单分子实时测序（SMRT）（PacBio）在我们 MHC 特征明确的西非黑猩猩队列中确定全长转录组。此外，通过应用 Cas9 介导的富集方法与牛津纳米孔技术的长读测序相结合，对 14 个单倍型的基因组组织进行了特征描述。
在该队列中，我们发现了 35 个未描述和 15 个已记录的等位基因，以及一个新的杂交基因。一些转录本受到进化保守的选择性剪接事件的影响。获得了有关基因区域动态（基因的位置和顺序）的详细信息，但是仅检测到五个新的基因区域配置。群体数据允许研究抑制性谱系 III KIR repertoire 中 MHC-C1 和 C2-表位特异性的分布，并且似乎偏向于 C2。
尽管已知基因区域进化迅速，就像在其他灵长类动物中观察到的那样，但我们的总体结论是，西非黑猩猩的基因组结构和 repertoire 仅表现出有限的或适度的变异。因此，影响黑猩猩 MHC Ⅰ类区域的古老选择可能也影响了基因系统。
