Evolutionary Venomics Lab | Kartik Sunagar

Primordial Knot
The deep-rooted origin of disulfide-rich spider venom toxins

Spider venoms are a complex concoction of enzymes, polyamines, inorganic salts, and disulfide-rich peptides (DRPs). Although DRPs are widely distributed and abundant, their evolutionary origin has remained elusive.

By evaluating DRPs under a comprehensive phylogenetic, structural and evolutionary framework, we have not only identified 78 novel spider toxin superfamilies but also provided the first evidence for their common origin.

We trace the origin of these toxin superfamilies to a primordial knot – which we named ‘Adi Shakti’, after the creator of the Universe according to Hindu mythology – 375 MYA in the common ancestor of Araneomorphae and Mygalomorphae.

This study provides fascinating insights into the early evolution and diversification of the spider venom arsenal.

In the Evolutionary Venomics Lab at the Centre for Ecological Sciences (CES), Indian Institute of Science (IISC), we investigate venomous animals and their venoms as model systems to address basic but broad questions in evolutionary biology and genetics. Using state-of-the-art technologies across multiple disciplines, we examine the fascinating evolutionary histories of the enigmatic lineages of venomous animals and their venoms.

A particular emphasis is placed on characterizing the composition, toxicity profiles and the evolutionary dynamics of venoms of the ‘big four’ snakes in India, as the lab will strive to deliver advanced antivenom with a commensurate improvement in safety, specificity, and affordability of treatment. The protein composition, and hence the pathogenic potential of venoms, can exhibit dramatic geographical variation, with different populations of the same species having starkly distinct venom profiles and, consequently, resulting in a significantly reduced antivenom efficiency. Therefore, the lab will unravel intra- and interspecific venom variability in medically significant Indian snakes and utilize this information for the molecular design of effective snakebite therapy.

The other broad aims of the lab include (a) investigating genomes, transcriptomes and proteomes of neglected venomous lineages (e.g., scorpions, spiders, centipedes, jellyfish, Hymenoptera, etc.) to understand the molecular basis of venom production, regulation, and evolutionary diversification; (b) understanding the genetic basis of venom resistance in the venomous animal and its prey/predators; (c) unravelling the evolutionary forces that have shaped the current distribution of venomous animals in the Indian subcontinent, and (d) investigating the therapeutic potential of venom proteins.