Departamento de Bioquímica y Biología Molecular - IUOPA, Universidad de Oviedo, C/ Fernando Bongera S/N, Oviedo, 33006, Spain.
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
BMC Evol Biol. 2020 Oct 19;20(1):135. doi: 10.1186/s12862-020-01698-1.
Through its ability to open pores in cell membranes, perforin-1 plays a key role in the immune system. Consistent with this role, the gene encoding perforin shows hallmarks of complex evolutionary events, including amplification and pseudogenization, in multiple species. A large proportion of these events occurred in phyla for which scarce genomic data were available. However, recent large-scale genomics projects have added a wealth of information on those phyla. Using this input, we annotated perforin-1 homologs in more than eighty species including mammals, reptiles, birds, amphibians and fishes.
We have annotated more than 400 perforin genes in all groups studied. Most mammalian species only have one perforin locus, which may contain a related pseudogene. However, we found four independent small expansions in unrelated members of this class. We could reconstruct the full-length coding sequences of only a few avian perforin genes, although we found incomplete and truncated forms of these gene in other birds. In the rest of reptilia, perforin-like genes can be found in at least three different loci containing up to twelve copies. Notably, mammals, non-avian reptiles, amphibians, and possibly teleosts share at least one perforin-1 locus as assessed by flanking genes. Finally, fish genomes contain multiple perforin loci with varying copy numbers and diverse exon/intron patterns. We have also found evidence for shorter genes with high similarity to the C2 domain of perforin in several teleosts. A preliminary analysis suggests that these genes arose at least twice during evolution from perforin-1 homologs.
The assisted annotation of new genomic assemblies shows complex patterns of birth-and-death events in the evolution of perforin. These events include duplication/pseudogenization in mammals, multiple amplifications and losses in reptiles and fishes and at least one case of partial duplication with a novel start codon in fishes.
穿孔素-1 通过打开细胞膜上的小孔，在免疫系统中发挥关键作用。与这一作用一致，编码穿孔素的基因表现出复杂进化事件的特征，包括在多个物种中扩增和假基因化。这些事件中的很大一部分发生在基因组数据稀缺的门中。然而，最近的大规模基因组学项目为这些门增加了大量信息。利用这一输入，我们在包括哺乳动物、爬行动物、鸟类、两栖动物和鱼类在内的 80 多种物种中注释了穿孔素-1 同源物。
我们在所有研究的物种中注释了超过 400 个穿孔素基因。大多数哺乳动物物种只有一个穿孔素基因座，其中可能包含一个相关的假基因。然而，我们在这个类群的不相关成员中发现了四个独立的小扩张。我们只能重建少数鸟类穿孔素基因的全长编码序列，尽管我们在其他鸟类中发现了这些基因的不完整和截断形式。在其余的爬行动物中，至少可以在三个不同的基因座中找到类似穿孔素的基因，其中包含多达 12 个拷贝。值得注意的是，哺乳动物、非鸟类爬行动物、两栖动物和可能的硬骨鱼至少共享一个穿孔素-1基因座，如侧翼基因所评估的那样。最后，鱼类基因组包含多个具有不同拷贝数和不同外显子/内含子模式的穿孔素基因座。我们还在几种硬骨鱼中发现了与穿孔素 C2 结构域具有高度相似性的较短基因的证据。初步分析表明，这些基因至少在进化过程中从穿孔素-1 同源物中两次出现。
新基因组组装的辅助注释显示了穿孔素进化过程中出生和死亡事件的复杂模式。这些事件包括哺乳动物中的复制/假基因化、爬行动物和鱼类中的多次扩增和丢失，以及鱼类中至少一次带有新起始密码子的部分复制。
