Convergent Evolution of Pain-Inducing Defensive Venom Components in Spitting Cobras

Abstract

<jats:p>Convergent evolution provides unparalleled insights into the selective drivers underlying evolutionary change. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of spitting cobras have independently evolved the ability to use venom as a defensive projectile. Using gene, protein and functional analyses, we show that the three spitting lineages possess venom characterized by an upregulation of PLA2 toxins, which potentiate the action of venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by exaptations. Notably, the timing of their origins suggests that defensive venom spitting may have evolved in response to the emergence of bipedal hominids in Africa and Asia.</jats:p>

The phylogeny, phylogeography, and diversification history of the westernmost Asian cobra (Serpentes: Elapidae: Naja oxiana) in the Trans‐Caspian region

“…Recently, Kazandjian et al. (2020) showed that spitting behavior in cobras has evolved independently in three spitting lineages as a defensive mechanism. Their results demonstrated that venom of cobras from these lineages was endowed with an upregulation of the activity of phospholipase A2 (PLA2) enzyme, a common toxin in venom of snakes, which triggers the activity of venom cytotoxins resulting in the activation of mammalian sensory neurons, thereby causing increased pain.…”

“…The distribution, demography, biology, ecology, and conservation status of the Caspian cobra remain largely undescribed. Even though some molecular studies have investigated Asian and African cobras (Kazandjian et al., 2020; Lin et al., 2008, 2012, 2014; Ratnarathorn et al., 2019; Santra et al., 2019; Wallach et al., 2009; Wüster et al., 2007), the phylogenetic and phylogeographic status, as well as the evolutionary history and population structure of the Caspian cobra in the Trans‐Caspian region, are still poorly known. The only study conducted on the genetic structure and phylogeny of the Caspian cobra in Iran, using 589 base pairs (bp) of the mitochondrial D‐loop region, revealed low genetic diversity and unstructured populations of the Iranian Caspian cobra (Shoorabi et al., 2017).…”

Coevolution between primates and venomous snakes revealed by α-neurotoxin susceptibility

“…Foraging hominins were likely to come in contact much more often with terrestrial, diurnally active neurotoxic elapid snakes such as cobras, which would defend themselves against perceived primate predators using their venom(22). The likely reduced susceptibility to α-neurotoxins from cobras might have driven cobras to develop a different kind of defense against hominins in the form of cytotoxins and spitting(15, 24). An evolved form of partial resistance meant that cobra venom was not an effective method to reduce hominin interactions thus cytotoxins and spitting might have evolved in response as a deterrent.…”

“…Conversely, there is evidence that venomous elapids have evolved some adaptations in response to primates. Spitting in cobras has evolved on three convergent occasions (twice within Naja and again Hemachatus) is a defensive trait that causes intense ocular pain and inflammation, which might have evolved in response to unique behavioural adaptations by anthropoids, particularly early hominines(15). Predation events by natural predators (e.g.…”

“…Predation events by natural predators (e.g. birds and other reptiles) of spitting cobras often occur, thus it seems that spitting is not an effective method against most predators(15). Intriguingly, the emergence of spitting in the Hemachatus (<17 mya), the African spitting Naja (~6.7 mya), and the Asian spitting Naja (~2.5 mya)(10), all coincided with the diverse emergence of terrestrial dwelling apes, including early hominids(16, 17), all of which occurred in habitats also frequented by largely terrestrial spitting cobras(18).…”