■免疫球蛋白A(IgA)是哺乳动物粘膜抗体,提供了抵御病原体的重要防线。有15个IgA亚类,欧洲兔子有一个极其复杂的IgA系统,比大多数其他哺乳动物复杂得多,只有一个IgA或,在类人猿的情况下,两个IgA亚类。类似于两个类人猿灵长类动物IGHA基因,由于通过Southern印迹分析发现了Sylvilagus属的多个IgA拷贝,因此兔IGHA基因的扩增似乎已经在祖先的lagomorph中开始,Lepus,还有奥乔托纳.
■为了更好地了解异形IgA的进化,我们测序了,第一次,两种Lepus物种的表达IgA基因,欧洲乳杆菌和加拿大乳杆菌。这些与15只兔子IgA同种型对齐,并进行了进化分析。获得的系统发育树表明,LepusIgA序列与兔IgA同种型聚集在一起,种间和种内的核苷酸遗传距离相似。Lepus和兔IgA的氨基酸序列的比较证实存在两个跨种多态性,并且兔和Lepus序列共享一个共同的遗传库。事实上,所研究的类IgA之间的主要差异在于铰链区的特征。
■我们获得的LepusIgA序列强烈表明,在常见的祖先物种中发生了轻体IGHA基因的大量扩展,然后在后代中得以维持。强大的选择压力导致IGHA基因异常扩张,但随后消退,导致后代中获得性多态性的维持,随后的分歧很小。这是一种独特的进化模式,其中一个古老的基因扩增已经维持了大约1800万年。
Immunoglobulin A (IgA) is the mammalian mucosal antibody, providing an important line of defense against pathogens. With 15 IgA subclasses, the European rabbit has an extremely complex IgA system, strikingly more complex than most other mammals, which have only one IgA or, in the
case of hominoids, two IgA subclasses. Similar to the two hominoid primate IGHA genes, the expansion of the rabbit IGHA genes appears to have begun in an ancestral lagomorph since multiple IgA copies were found by Southern blot analysis for the genera Sylvilagus, Lepus, and Ochotona.
To gain a better insight into the extraordinary lagomorph IgA evolution, we sequenced, for the first time, expressed IgA genes for two Lepus species, L. europaeus and L. granatensis. These were aligned with the 15 rabbit IgA isotypes, and evolutionary analyses were conducted. The obtained phylogenetic tree shows that the Lepus IgA sequences cluster with and among the rabbit IgA isotypes, and the interspecies and intraspecies nucleotide genetic distances are similar. A comparison of the amino acid sequences of the Lepus and rabbit IgA confirms that there are two trans-species polymorphisms and that the rabbit and Lepus sequences share a common genetic pool. In fact, the main differences between the studied leporids IgAs reside in the characteristics of the hinge region.
The Lepus IgA sequences we have obtained strongly suggest that the great expansion of the leporid IGHA genes occurred in a common ancestral species and was then maintained in the descendants. A strong selective pressure caused the extraordinary expansion of the IGHA genes but then subsided, leading to the maintenance of the acquired polymorphisms in the descendants, with little subsequent divergence. This is a unique evolutionary pattern in which an ancient gene expansion has been maintained for approximately 18 million years.