Multiple mutations in the Nav1.4 sodium channel of New Guinean toxic birds provide autoresistance to deadly batrachotoxin

Abstract

Toxicity has evolved multiple times across the tree of life and serves important functions related to hunting, defence and parasite deterrence. Toxins are produced either in situ by the toxic organism itself or associated symbionts, or acquired through diet. The ability to exploit toxins from external sources requires adaptations that prevent toxic effects on the consumer (autoresistance). Here, we examine genomic adaptations that could facilitate autoresistance to the diet‐acquired potent neurotoxic alkaloid batrachotoxin (BTX) in New Guinean toxic birds. Our work documents two new toxic bird species and shows that toxic birds carry multiple mutations in the SCN4A gene that are under positive selection. This gene encodes the most common vertebrate muscle Nav channel (Nav1.4). Molecular docking results indicate that some of the mutations that are present in the pore‐forming segment of the Nav channel, where BTX binds, could reduce its binding affinity. These mutations should therefore prevent the continuous opening of the sodium channels that BTX binding elicits, thereby preventing muscle paralysis and ultimately death. Although these mutations are different from those present in Neotropical Phyllobates poison dart frogs, they occur in the same segments of the Nav1.4 channel. Consequently, in addition to uncovering a greater diversity of toxic bird species than previously known, our work provides an intriguing example of molecular‐level convergent adaptations allowing frogs and birds to ingest and use the same neurotoxin. This suggests that genetically modified Nav1.4 channels represent a key adaptation to BTX tolerance and exploitation across vertebrates.

Exotic predators can sequester and use novel toxins from exotic non-coevolved prey

“…Ten prickly pear clusters infested by cochineal bugs were located and selected in semi-natural areas or field margins in eastern Spain (electronic supplementary material, figure S1). We sampled the clusters during two consecutive years (2020 and 2021) in late spring (10-20 June), mid-summer (27 July-5 August) and mid-autumn (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). In each prickly pear cluster, sixty cladodes were observed and those infested by more than approximately 50 cochineal bugs were sampled to identify potential predators.…”

“…For example, in Rhabdophis snakes, Rhabdophis tigrinus sequesters defensive steroids from toads, while Rhabdophis nuchalis sequesters these substances from fireflies [18]. Several species belonging to four families of passerine birds are believed to sequester batrachotoxin alkaloids from Choresine beetles [10,15]. Several amphibian families acquire alkaloids from different sources of arthropods, including beetles, ants or mites [11].…”

Toxic to the touch: The makings of lethal mantles in pitohui birds and poison dart frogs

“…In their recent study, Bodawatta et al. (2023) make a major contribution to the study of toxin co‐option. They aimed to shed light on the extent of convergent evolution in the sequestration of the neurotoxic steroidal alkaloid BTX in the skin and feathers of Papua New Guinean toxic birds and Neotropical Phyllobates poison dart frogs.…”

Are some brightly coloured European wild birds toxic?

“…The toxins are especially concentrated in the breast and belly feathers, such that these not only protect the adult birds, but may also rub off on eggs and young in the nest (Dumbacher et al, 2000;Yeung et al, 2022). That such warning colouration is shown by other, poisonous pitohuis in New Guinea (Jønsson et al, 2008), as well as bird species of other genera, e.g., the blue-capped ifrit, Ifrita kowaldi (De Vis) (Dumbacher et al, 2000;Bodawatta et al, 2023) appears to be a case of convergent evolution leading to Müllerian mimicry, i.e., gaining additional protection by mimicking other contrastingly, brightly coloured noxious/venomous animals (Cott, 1940;Baker and Parker, 1979;Hedley and Caro, 2022). The Hooded Pitohui's defence is reinforced by a strong odour (Dumbacher et al, 1992).…”