Diya Adhikary, Amity University Kolkata
The etymology of “venom” is associated with polytheistic cults that highlighted the accomplishment of desires sometimes aided by “love potions”. This was later interpolated with the word “poison”. Venom is defined as a mixture of toxic enzymes and various other proteins. It is produced in certain specific glands in the body of a poisonous/venomous animal. Various factors like geography, diet, predator pressure, evolutionary arms race, and phylogenetic history, underpin the diversification of venoms. It is not likely, but new research reveals that humans have the toolkit to produce venom.
The key factor behind venomous humans – Kallikrein protein
It has been deciphered that the human salivary glands contain venom gland gene expression preserved for several thousands of years. Due to evolutionary mechanisms, the tissues have transformed with time to perform different functions and hence, human salivary glands have their links to the snake’s venom glands. Humans already produce a key protein named kallikrein, which is used in many venom systems. Kallikreins, a kind of protein that has the ability to cleave peptide bonds in proteins. In simple words, it can be said that kallikreins are proteins that can digest other proteins.
The kallikrein protein was first isolated and named by researcher Eugen Werle from the pancreas of humans and several other animals. This specific protein has been found in the venoms of some animals such as snakes, solenodons (a poisonous insectivorous mammal), northern-short-tailed shrews, etc. Further, the secretions of the poison glands of Lagoa Crispata (a caterpillar) are found to be kallikrein in nature. The connection of the kallikrein protein to “venom in humans” comes from the fact that humans contain 15 known tissue kallikrein genes (KLK1-KLK15).
So kallikreins can be said to be the natural starting point for the theoretical concept of venomous humans. This protein is excessively stable in nature and thus it does not get malfunction random mutations in it. Thus, it is quite easy to get advantageous mutations of kallikreins that make venom all the more painful and deadly. One such effect of kallikreins is that it leads to a sharp drop in blood pressure levels.
Molecular biology related to venomous humans
Mammals (such as humans, mice, chimpanzees, dogs) and snakes share a set of genes that are similarly controlled and show similar activities despite being different. Though the origin of an oral venom system is not yet experimentally verified, yet certain studies have shown that it is likely to have originated from a regulatory gene network, known as the “metavenom network”, which is conserved across amniotes. The “metavenom network” represents an assemblage of housekeeping genes (over 3000) that are strongly associated with toxin genes and protein folding and modification. The genes involved in this “metavenom network” have greater functional relevance than those that are simply up-regulated in the venom gland. Comparative transcriptomics has revealed that the network is conserved between venom glands (snakes) and salivary glands (mammals). This again hints at the fact that though these tissues have different functions, they share a common regulatory core (since their common ancestry).
The above image is that of a viper snake. The study on housekeeping genes that were associated with the metavenom network was carried out on a viper.
The “metavenom network” is composed of a group of molecules of DNA, RNA, or protein. These regulatory networks act as regulators and control the levels of gene expression. The functionality of a cell is determined by the process through which they produce their mRNA or proteins. These genes not only play a vital role in protecting cells from the stress caused by excessive protein production (venom protein) but also regulate protein folding (the process by which long chains of amino acids fold in a specific way in order to provide firmness to the protein).
Conclusion
So, this brings us to the question that: “Can we expect the existence of venomous humans in the future?” For an answer to this question, evolutionary geneticist Agneesh Barua can be quoted, who said that “Essentially, we have all the building blocks in place. Now it’s up to evolution to take us there.”
Also read: Relationship between PDI gene family and ER stress
References:
- Barua, A., & Mikheyev, A. S. (2021). An ancient, conserved gene regulatory network led to the rise of oral venom systems. Proceedings of the National Academy of Sciences of the United States of America, 118(14), e2021311118. https://doi.org/10.1073/pnas.2021311118
- Raspi G. (1996). Kallikrein and kallikrein-like proteinases: purification and determination by chromatographic and electrophoretic methods. Journal of chromatography. B, Biomedical applications, 684(1-2), 265–287. https://doi.org/10.1016/0378-4347(96)00144-2
- Lamdin, J. M., Howell, D. E., Kocan, K. M., Murphey, D. R., Arnold, D. C., Fenton, A. W., Odell, G. V., & Ownby, C. L. (2000). The venomous hair structure, venom and life cycle of Lagoa crispata, a puss caterpillar of Oklahoma. Toxicon : official journal of the International Society on Toxinology, 38(9), 1163–1189. https://doi.org/10.1016/s0041-0101(99)00195-6
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