TotM: Zebrafish ferrochelatase and vampirism

 Drácula-de-Bram-Stoker-2-las-cosas-felices-1024x592.pngVampires are one of the most universal mythic creatures, appearing in one way or another in pretty much any cultures. In a general sense, a vampire is an undead that needs to drink blood. The myth entered the modernity with Dracula, the great gothic novel written by Bram Stoker. The novel was based on the legends spanned around the figure of a historical character, Vlad Tepes. Vlad is remembered by the people of Romania as a fair governor; while in Turkey it’s remembered as Vlad the Impaler, for whatever reason. Coming back to Dracula, the novel character, it helped unify the phenotypic traits of vampires around the world. These traits included a myriad of supernatural abilities, but also a few important weak spots. And from all the vulnerabilities that Dracula and all vampires have, the most important is the fact that sunlight would destroy him instantly.

 

Beyond literary monsters based on controversial historical figures, the vampire myth universality seem to stem from certain real life phenomena. One of these is erythropoietic porphyria (also known as Gunther disease), a haunting genetic disorder that causes, among many other symptoms, severe anemia and photosensitivity. The disease is caused by a mutation in one of the steps of the haemoglobin biosynthesis pathway, which in turn causes the accumulation of intermediate species in the body that are photoreactive and toxic. And anemia, naturally. The sun lesions and many other characteristics of the disease can be easily mapped to some of the traditional vampire look.

 

Zebrafish.jpgGenetic screening of erythropoietic genes have been performed in Danio rerio, which led to the description of mutants with anemia and high mortality when kept under normal light conditions. Unsurprisingly they called this gene “dracula”, although it’s generally preferred the term ferrochelatase. The embryos present accumulation of protoporphyrin IX, an intermediate that breaks under light, leading to a similar profile to patients with Gunther disease.

Heme_delocalized.png

 

The heme complex is essential for virtually every living being. Beyond their obvious functions in oxygen transport in vertebrate blood, it is also present in many enzymes, such a cytochromes. The heme group is quite complex, though, an enormous organic ring with a quartet of nitrogen atoms that holds a precious iron in its center. The biosynthesis of this organometallic compound is well characterized, a complex set of reactions that makes iron the highest demanded of the trace bioelements. The pathway of such an essential biochemical compound, the genes are highly conserved, as we can observe in our tree of the month, from the zebrafish phylome. You can find many more stories in phylomeDB!



 

 

 

 

References:

https://www.ncbi.nlm.nih.gov/pubmed/28553927

https://www.ncbi.nlm.nih.gov/pubmed/28591648

https://www.ncbi.nlm.nih.gov/pubmed/22705943

https://www.ncbi.nlm.nih.gov/pubmed/20862391

https://www.ncbi.nlm.nih.gov/pubmed/10985389

 

Pictures:

Photogram from Bram Stoker's Dracula (1992)