Kunchala Srinivasa Reddy, van Dijk Albert, Veldhuizen Edwin J A, Donnellan Stephen C, Haagsman Henk P, Orgeig Sandra
Centre for Cancer Diagnostics and Therapeutics, UniSA Cancer Research Institute, UniSA Clinical and Health Sciences, University of South Australia, SA, 5001, Australia.
Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Dev Comp Immunol. 2023 Feb;139:104582. doi: 10.1016/j.dci.2022.104582. Epub 2022 Oct 25.
The air-liquid interface of the mammalian lung is lined with pulmonary surfactants, a mixture of specific proteins and lipids that serve a dual purpose-enabling air-breathing and protection against pathogens. In mammals, surfactant proteins A (SP-A) and D (SP -D) are involved in innate defence of the lung. Birds seem to lack the SP-D gene, but possess SP-A2, an additional SP-A-like gene. Here we investigated the evolution of the SP-A and SP-D genes using computational gene prediction, homology, simulation modelling and phylogeny with published avian and other vertebrate genomes. PCR was used to confirm the identity and expression of SP-A analogues in various tissue homogenates of zebra finch and turkey. In silico analysis confirmed the absence of SP-D-like genes in all 47 published avian genomes. Zebra finch and turkey SP-A1 and SP-A2 sequences, confirmed by PCR of lung homogenates, were compared with sequenced and in silico predicted vertebrate homologs to construct a phylogenetic tree. The collagen domain of avian SP-A1, especially that of zebra finch, was dramatically shorter than that of mammalian SP-A. Amphibian and reptilian genomes also contain avian-like SP-A2 protein sequences with a collagen domain. NCBI Gnomon-predicted avian and alligator SP-A2 proteins all lacked the collagen domain completely. Both avian SP-A1 and SP-A2 sequences form separate clades, which are most closely related to their closest relatives, the alligators. The C-terminal carbohydrate recognition domain (CRD) of zebra finch SP-A1 was structurally almost identical to that of rat SP-A. In fact, the CRD of SP-A is highly conserved among all the vertebrates. Birds retained a truncated version of mammalian type SP-A1 as well as a non-collagenous C-type lectin, designated SP-A2, while losing the large collagenous SP-D lectin, reflecting their evolutionary trajectory towards a unidirectional respiratory system. In the context of zoonotic infections, how these evolutionary changes affect avian pulmonary surface protection is not clear.
哺乳动物肺的气液界面衬有肺表面活性剂，这是一种特定蛋白质和脂质的混合物，具有双重作用——使呼吸空气并抵御病原体。在哺乳动物中，表面活性剂蛋白A（SP-A）和D（SP-D）参与肺部的固有防御。鸟类似乎缺乏SP-D基因，但拥有SP-A2，这是一个额外的类似SP-A的基因。在这里，我们使用计算基因预测、同源性、模拟建模和系统发育分析，结合已发表的鸟类和其他脊椎动物基因组，研究了SP-A和SP-D基因的进化。PCR用于确认斑胸草雀和火鸡各种组织匀浆中SP-A类似物的身份和表达。计算机分析证实，在所有47个已发表的鸟类基因组中均不存在类似SP-D的基因。通过肺匀浆的PCR确认的斑胸草雀和火鸡SP-A1和SP-A2序列，与已测序和计算机预测的脊椎动物同源物进行比较，以构建系统发育树。鸟类SP-A1的胶原结构域，尤其是斑胸草雀的，比哺乳动物SP-A的明显短。两栖动物和爬行动物的基因组也包含具有胶原结构域的类似鸟类的SP-A2蛋白序列。NCBI Gnomon预测的鸟类和短吻鳄SP-A2蛋白完全缺乏胶原结构域。鸟类的SP-A1和SP-A2序列都形成了单独的进化枝，它们与最亲近的亲属短吻鳄关系最为密切。斑胸草雀SP-A1的C端碳水化合物识别结构域（CRD）在结构上几乎与大鼠SP-A的相同。事实上，SP-A的CRD在所有脊椎动物中高度保守。鸟类保留了哺乳动物型SP-A1的截短版本以及一种非胶原C型凝集素，即SP-A2，同时失去了大型胶原SP-D凝集素，这反映了它们向单向呼吸系统进化的轨迹。在人畜共患感染的背景下，这些进化变化如何影响鸟类肺部表面保护尚不清楚。
