Ancestral reconstruction reveals catalytic inactivation of activation-induced cytidine deaminase concomitant with cold water adaption in the Gadiformes bony fish.
Ancestral reconstruction reveals catalytic inactivation of activation-induced cytidine deaminase concomitant with cold water adaption in the Gadiformes bony fish.
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DOI：
10.1186/s12915-022-01489-8
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发表时间：
2022-12-27
期刊：
影响因子：
5.4
通讯作者：
Larijani, Mani
中科院分区：
文献类型：
--
作者：
Ghorbani, Atefeh;Khataeipour, S. Javad;Solbakken, Monica H.;Huebert, David N. G.;Khoddami, Minasadat;Eslamloo, Khalil;Collins, Cassandra;Hori, Tiago;Jentoft, Sissel;Rise, Matthew L.;Larijani, Mani
脊椎动物抗体亲和力的成熟需要酶激活诱导胞苷脱氨酶(AID)，AID通过突变免疫球蛋白基因座启动二次抗体多样化。援助驱动的抗体多样化在有颌骨的脊椎动物中是保守的，因为骨骼和软骨鱼类。最近报告了两个例外，即笛鱼和角鱼，其中编码AID的Aicda基因已经丢失。这两个病例都与异常生殖行为有关，包括男性怀孕和性寄生虫。大西洋鳕科的几种冷水鱼携带一种编码全长酶的aicda基因，但缺乏亲和力成熟的抗体，并依赖于具有广泛抗原性的抗体。因此，我们检查了他们的AID的功能。通过结合基因组学、转录学、免疫反应性和功能酶学，我们证明了该大西洋鳕鱼和相关鱼类的AID具有极低的催化活性或没有催化活性。通过对71种AID酶的祖先重建和功能酶学研究，我们发现这种酶的失活可能发生在真正的鳕鱼家族(鳕科)从其祖先的鸭形目中出现的较近的时间。我们发现，这种AID失活不仅与先前在鸭形目动物中发现的关键适应性免疫基因的丢失和固有免疫基因和细胞免疫基因的扩张是一致的，而且进一步反映在这些鱼类的基因组中，其免疫球蛋白可变区基因中丢失了AID有利的序列基序。最近在两种鱼类中发现的aicda基因的缺失，挑战了在有颌骨的脊椎动物中，由艾滋病驱动的二次抗体多样化是绝对保守的范式。这些物种具有不寻常的生殖行为，形成了一定的免疫丧失的进化压力，以避免组织排斥。我们在这里报告了一个例子，在一个常规繁殖的脊椎动物中，AID的催化失活和功能丧失而不是基因丢失。我们的数据表明，扩大的先天免疫力，加上寒冷环境中较低的致病压力，缓解了保持强大的二次抗体多样化的压力。我们认为，在这种独特的情况下，AID介导的基因组范围的附带损伤将形成一种丧失AID功能的进化压力。网上版载有补充材料，可在10.1186/s12915-022-01489-8查阅。
Antibody affinity maturation in vertebrates requires the enzyme activation-induced cytidine deaminase (AID) which initiates secondary antibody diversification by mutating the immunoglobulin loci. AID-driven antibody diversification is conserved across jawed vertebrates since bony and cartilaginous fish. Two exceptions have recently been reported, the Pipefish and Anglerfish, in which the AID-encoding aicda gene has been lost. Both cases are associated with unusual reproductive behavior, including male pregnancy and sexual parasitism. Several cold water fish in the Atlantic cod (Gadinae) family carry an aicda gene that encodes for a full-length enzyme but lack affinity-matured antibodies and rely on antibodies of broad antigenic specificity. Hence, we examined the functionality of their AID. By combining genomics, transcriptomics, immune responsiveness, and functional enzymology of AID from 36 extant species, we demonstrate that AID of that Atlantic cod and related fish have extremely lethargic or no catalytic activity. Through ancestral reconstruction and functional enzymology of 71 AID enzymes, we show that this enzymatic inactivation likely took place relatively recently at the emergence of the true cod family (Gadidae) from their ancestral Gadiformes order. We show that this AID inactivation is not only concordant with the previously shown loss of key adaptive immune genes and expansion of innate and cell-based immune genes in the Gadiformes but is further reflected in the genomes of these fish in the form of loss of AID-favored sequence motifs in their immunoglobulin variable region genes. Recent demonstrations of the loss of the aicda gene in two fish species challenge the paradigm that AID-driven secondary antibody diversification is absolutely conserved in jawed vertebrates. These species have unusual reproductive behaviors forming an evolutionary pressure for a certain loss of immunity to avoid tissue rejection. We report here an instance of catalytic inactivation and functional loss of AID rather than gene loss in a conventionally reproducing vertebrate. Our data suggest that an expanded innate immunity, in addition to lower pathogenic pressures in a cold environment relieved the pressure to maintain robust secondary antibody diversification. We suggest that in this unique scenario, the AID-mediated collateral genome-wide damage would form an evolutionary pressure to lose AID function. The online version contains supplementary material available at 10.1186/s12915-022-01489-8.
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