蜱是一类在世界范围内广泛分布，专性吸食脊椎动物血液为生的体外寄生虫。它们是细菌、病毒、蠕虫等病原体的传播者，能够导致多种人类和动物疾病，因此在动物流行病学上具有重要意义。蜱主要分为软蜱和硬蜱，它们具有不同的吸血策略，软蜱是短时程吸血（几分钟到几小时），而硬蜱是长时程吸血（几天甚至上周）。
Kunitz/BPTI蛋白大量存在于蜱类唾液腺中并在吸血过程中发挥着重要作用。在软蜱和硬蜱中，Kunitz/BPTI蛋白具有不同的功能和结构域组成。Kunitz/BPTI蛋白的这种功能分化和结构域差异是怎样形成的，该家族的进化是否与软蜱和硬蜱中不同的吸血策略相关，至今还不清楚。
昆明动物研究所遗传资源与进化国家重点实验室生物信息学和系统生物学研究组的博士生代绍兴和张爱娣，在黄京飞研究员的指导下，系统地研究了在肩突硬蜱（Ixodes scapularis）中Kunitz/BPTI基因家族的进化，扩张和表达。研究揭示了Kunitz/BPTI基因家族在软蜱和硬蜱中存在的巨大差异。多结构域蛋白是在软蜱和硬蜱分化后才在硬蜱中进化而来。Group II and III 基因只存在于硬蜱属（Ixodes)中，并且在硬蜱的长时程吸血过程中表达上调。正选择驱动了Kunitz/BPTI基因家族的进化，在这过程中group II基因进化出了调控离子通道的新功能，通过增强硬蜱的吸血效率而在蜱类吸血过程中发挥作用。因此这项研究结果提示Kunitz/BPTI基因家族在软蜱和硬蜱中存在的巨大差异与硬蜱进化出的长时程吸血行为相关。最后，我们鉴定出来的六个差异表达基因可以作为控制蜱类的候选靶基因。
该研究结果目前发表于BMC Evolutionary Biology (该研究得到了科技部973项目，国家自然科学基金等的资助。（生物谷 Bioon）
doi:10.1186/1471-2148-12-4
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PMID:
Evolution, expansion and expression of the Kunitz/BPTI gene family associated with long-term blood feeding in Ixodes Scapularis
Shao-Xing Dai, Ai-Di Zhang, and Jing-Fei Huang
Background
Recent studies of the tick saliva transcriptome have revealed the profound role of salivary proteins in blood feeding. Kunitz/BPTI proteins are abundant in the salivary glands of ticks and perform multiple functions in blood feeding, such as inhibiting blood coagulation, regulating host blood supply and disrupting host angiogenesis. However, Kunitz/BPTI proteins in soft and hard ticks have different functions and molecular mechanisms. How these differences emerged and whether they are associated with the evolution of long-term blood feeding in hard ticks remain unknown.
Results
In this study, the evolution, expansion and expression of Kunitz/BPTI family in Ixodes scapularis were investigated. Single- and multi-domain Kunitz/BPTI proteins have similar gene structures. Single-domain proteins were classified into three groups (groups I, II and III) based on their cysteine patterns. Group I represents the ancestral branch of the Kunitz/BPTI family, and members of this group function as serine protease inhibitors. The group I domain was used as a module to create multi-domain proteins in hard ticks after the split between hard and soft ticks. However, groups II and III, which evolved from group I, are only present and expanded in the genus Ixodes. These lineage-specific expanded genes exhibit significantly higher expression during long-term blood feeding in Ixodes scapularis. Interestingly, functional site analysis suggested that group II proteins lost the ability to inhibit serine proteases and evolved a new function of modulating ion channels. Finally, evolutionary analyses revealed that the expansion and diversification of the Kunitz/BPTI family in the genus Ixodes were driven by positive selection.
Conclusions
These results suggest that the differences in the Kunitz/BPTI family between soft and hard ticks may be linked to the evolution of long-term blood feeding in hard ticks. In Ixodes, the lineage-specific expanded genes (Group II and III) lost the ancient function of inhibiting serine proteases and evolved new functions to adapt to long-term blood feeding. Therefore, these genes may play a profound role in the long-term blood feeding of hard ticks. Based our analysis, we propose that the six genes identified in our study may be candidate target genes for tick control.
