Futas Jan, Oppelt Jan, Vychodilova Leona, Burger Pamela, Horin Petr
Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno (VETUNI), Brno, Czech Republic.
Research Group Animal Immunogenomics, CEITEC VETUNI, Brno, Czech Republic.
HLA. 2022 Jul;100(1):37-51. doi: 10.1111/tan.14595. Epub 2022 Mar 27.
Natural killer cells and cytotoxic T lymphocytes are the main cell populations of the immune system able to directly kill target cells via cytotoxic granules. Different mammalian species may differ in specific features of their pore-forming protein (perforin) and granule-bound serine proteases (granzymes). One perforin gene (PRF1) and four genes encoding granzymes A, B, H, and K (GZMA, GZMB, GZMH, GZMK) were identified in the reference genomes of felids. The objective of this work was to characterize the genes PRF1, GZMA and GZMB in a panel of 17 felid species by next-generation re-sequencing. A search of available felid genomes (17 species) retrieved the coding sequences of these genes for comparison to our data. Both sets of sequences or their combinations (23 species) were used for phylogenetic and selection analyses. Nucleotide PRF1, GZMA and GZMB sequences showed high similarities between felid species (over 95% identity). All trees derived from coding sequences expressed phylogenetic relationships corresponding to the zoological taxonomy of the Felidae, except GZMA. No effects of positive selection were detected in the genes studied, however, effects of purifying selection were observed for PRF1 and GZMA. The conservation of PRF1 is in agreement with its critical biological function. The differentiation observed between granzyme sub-families may reflect an adaptation to pathogen variation. The need to maintain important gene functions and at the same time cope with various pathogens may lead to an equilibrium between positive and negative selective pressures acting on GZMB. The within-species variability in wild felid populations merits further investigation.
自然杀伤细胞和细胞毒性T淋巴细胞是免疫系统中能够通过细胞毒性颗粒直接杀伤靶细胞的主要细胞群体。不同的哺乳动物物种在其成孔蛋白（穿孔素）和颗粒结合丝氨酸蛋白酶（颗粒酶）的特定特征上可能存在差异。在猫科动物的参考基因组中鉴定出了一个穿孔素基因（PRF1）和四个编码颗粒酶A、B、H和K的基因（GZMA、GZMB、GZMH、GZMK）。这项工作的目的是通过下一代重测序对17种猫科动物中的PRF1、GZMA和GZMB基因进行特征分析。搜索现有的猫科动物基因组（17个物种），获取这些基因的编码序列以与我们的数据进行比较。两组序列或其组合（23个物种）用于系统发育和选择分析。核苷酸PRF1、GZMA和GZMB序列在猫科动物物种之间显示出高度相似性（同一性超过95%）。除GZMA外，所有从编码序列推导的树都表达了与猫科动物动物分类学相对应的系统发育关系。在所研究的基因中未检测到正选择的影响，然而，在PRF1和GZMA中观察到了纯化选择的影响。PRF1的保守性与其关键的生物学功能一致。颗粒酶亚家族之间观察到的分化可能反映了对病原体变异的适应。维持重要基因功能同时应对各种病原体的需求可能导致作用于GZMB的正负选择压力之间的平衡。野生猫科动物种群内的种内变异性值得进一步研究。
