The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation

The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation
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自然杀手复合体的演变;

DOI:
10.1101/069922
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发表时间:
2016
期刊:
--
影响因子:
--
通讯作者:
Schwartz J
Schwartz J
中科院分区:
--
文献类型:
--
作者:
Schwartz J

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自然杀伤(NK)细胞是具有一系列生物学作用(包括基本免疫功能)的多种淋巴细胞群体。NK细胞多样性部分是由调节活化和功能的细胞表面受体的差异表达产生的,包括NK复合物(NKC)内编码的C型凝集素受体的多个亚家族。除了啮齿动物和灵长类谱系外,对NKC的基因内容知之甚少,除了它在哺乳动物群体之间似乎差异极大。我们比较了哺乳动物物种之间的NKC结构,使用牛和山羊的新的高质量基因组草图组装;重新注释的绵羊,猪和马的基因组组装;以及已发表的人类,大鼠和小鼠狐猴NKC。主要的NKC基因在很大程度上是在所有8个物种中的相同位置,具有显着的独立的扩展和物种之间的删除,使我们能够提出一个模型NKC进化哺乳动物辐射。反刍动物物种,牛和山羊,已经独立地进化出了第二个KLR Clocus,两侧是KLR A和KLR R J,并且一个新的KLRH样基因已经获得了激活尾巴。这种新基因在牛体内复制了几次,而其他激活受体基因则被选择性地破坏。牛的靶向基因组富集鉴定了集中在预测的细胞外配体结合结构域的NKC基因之间不同水平的等位基因多态性。这种新的重组和等位基因多态性与平衡选择下的NKC进化一致,表明这种多样性影响个体免疫应答,并可能影响病原体感染和疫苗接种的不同结果。
Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a secondKLRClocus flanked byKLRAandKLRJ, and a novelKLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination.
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影响因子: 3.7
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