Hello, kitty: could cat allergy be a form of intoxication?

Abstract Background: The relationship between slow loris (Nycticebus spp.) venom (BGE protein) and the major cat allergen (Fel d 1) from domestic cat (Felis catus) is known for about two decades. Along this time, evidence was accumulated regarding convergences between them, including their almost identical mode of action. Methods: Large-scale database mining for Fel d 1 and BGE proteins in Felidae and Nycticebus spp., alignment, phylogeny proposition and molecular modelling, associated with directed literature review were assessed. Results: Fel d 1 sequences for 28 non-domestic felids were identified, along with two additional loris BGE protein sequences. Dimer interfaces are less conserved among sequences, and the chain 1 shows more sequence similarity than chain 2. Post-translational modification similarities are highly probable. Conclusions: Fel d 1 functions beyond allergy are discussed, considering the great conservation of felid orthologs of this protein. Reasons for toxicity being found only in domestic cats are proposed in the context of domestication. The combination of the literature review, genome-derived sequence data, and comparisons with the venomous primate slow loris may point to domestic cats as potentially poisonous mammals.

**背景**：学界对懒猴（Nycticebus spp.）毒液（BGE蛋白）与家猫（Felis catus）来源的主要猫过敏原（Fel d 1）之间的关联已有约二十年的认知。在此期间，学界积累了二者存在趋同演化的相关证据，包括二者近乎完全一致的作用模式。
**方法**：本研究针对猫科（Felidae）和懒猴属（Nycticebus spp.）物种中的Fel d 1与BGE蛋白开展大规模数据库挖掘，结合定向文献综述，完成了序列比对、系统发育推导及分子建模分析。
**结果**：本研究共鉴定出28种非家猫科动物的Fel d 1序列，以及额外2条懒猴BGE蛋白序列。序列比对显示，二聚体界面的保守性相对较低，且1号链的序列相似性高于2号链。二者的翻译后修饰极有可能存在相似性。
**结论**：鉴于该蛋白在猫科直系同源基因中的高度保守性，本研究探讨了Fel d 1超越过敏反应之外的功能。同时，结合家猫的驯化背景，本研究提出了仅家猫表现出毒性的潜在原因。综合文献综述、基因组来源的序列数据，以及与有毒灵长类懒猴的对比分析，本研究提示家猫可能是具有潜在毒性的哺乳动物。