Why honey badgers don't give a sh** about venomous snake bites (along with possums, mongooses and some skunks)

Ryan Baker-Branstetter

Most animals would think that being bitten by a venomous snake would definitely constitute a bad day.  Then again, most animals aren't the honey badger, Mellivora capensis, the biggest bad ass of the animal kingdom.  As Randall so eloquently explains, honey badgers are resistant to the effects of the venom of certain vipers and cobras.  Venom resistance as a predatory adaptation is shared by a limited number of mammals including possums and mongooses, and this resistance is mediated in multiple ways at the molecular level.  Snake venom is a complex substance composed of multiple toxins the induce effects such as hemorrhaging, cardiac and respiratory failure, and paralysis.  The honey badger is part of an exclusive group that actively hunts venomous snakes and has developed venom resistance to prevent the predator from becoming the prey.

Educational video about the honey badger (Warning: offensive language)

One on the first questions to address when discussing venom resistance in predators is why this would be an advantageous adaptation.  First of all, studies have shown that venomous snake species can be the most abundant snake species in a given area, demonstrated in the Americas, Europe and Africa.  Along with their abundance, snakes possess thin and flexible skin and their bones are small and fragile, so mammals don't require specialized jaws for snake predation.  Venom is dangerous when confronting a snake directly because the fangs deliver this substance directly to the bloodstream, but many of the toxins in snake venom can be broken down by digestion and is usually regarded as a predatory adaptation rather than a defensive one.  Therefore, venom resistance only comes into play when the predator is bitten by the snake while trying to consume it.  All mammals known to have venom resistance at this time don't consume venomous snakes for a majority of their diet, but this adaptation allows an abundant food source to be utilized.

All right, maybe mongooses are pretty badass too...

All right, we've talked a lot about venomous snakes without actually defining what venom is, so let's do that.  Venom is complex secretion that is delivered using the snakes fangs, usually consisting of 30-40 toxins representing 8-12 protein families.  There are two families of venomous snakes: elapids, which include cobras, kraits, and mambas, and viperids, which include the vipers and pit vipers.  Venoms in both families tend to have different effects, with elapid venom containing more neurotoxins and cardiotoxins, while viperid venom tends to cause hemorrhaging and factors that prevent or accelerate blood clotting.  At the molecular level, snake toxins break down proteins and fatty acids, bind to molecules found in the serum, and block receptors that are necessary for muscle contraction.  With such varied effects, mechanisms of resistance that have evolved are similarly complex.

Venom resistance in venomous snake predators is shared by 48 species of mammals in 14 families and includes groups such as opossums, hedgehogs, mongooses, skunks, and of course, the honey badger and other related species in the weasel family.  Resistance seems to be mediated at the molecular level, since there is no obvious morphological specialization that is shares between the resistant species. 

Two types of assays are currently used to determine resistance.  Direct immunity is determined by injecting the species with measured amounts of venom and assessing survival.  "Transferrable" immunity is determined by incubating blood from the evaluated species with measured amounts of venom and then assessing it for biochemical venom activity or injecting the sample into mice and assessing survival.  Certain species like the Egyptian mongoose demonstrate direct immunity to Palestinian Viper venom, but its serum showed no neutralizing activity, suggesting that much of the resistance for this species was not mediated through the serum. 

Extensive studies have been done of in the North American possum, which shows resistance to pitviper venom.  It was discovered that one of the main molecules responsible was a protein called Oprin which along with 6 other highly-related proteins, neutralized much of the destructive properties of pitviper venom.  Further studies with the North American possum showed that it was not resistant to all venoms, and it was susceptible to venom from vipers and elapids.  While the mechanism is still not completely known, honey badgers kill and eat both cobra and vipers, further cementing their status as a bad ass.  And if you still don't believe me, you should ask these 6 lions that thought it would be a good idea to harass a pair of honey badgers.

Venom resistance seems like it would be a helpful trait for both predators and prey of venomous snakes to have, but very limited resistance is seen throughout the mammal community.  One of the challenges of developing venom resistance lies with the conserved nature of many serum proteins.  If they are modified in a way that would avoid snake venom binding, they might also be incompatible with the normal physiological function of the animal.  To make things even more challenging, the varied effects of snake venom means that resistance to a limited number of toxins would not be effective in preventing all the negative effects.  Venom resistance in mammals seems to have evolved only in predators and some prey with sustained predatory interactions.  One would think that  venom might be more important when used successfully during predator-prey interactions when the snake is the predator.  However, genetic research has yielded interesting results when analyzing the loci of genes found to be important in venom effects and venom resistance.  Rapid evolution is usually indicated when there is a high ratio of replacement to silent substitutions, and it has recently been demonstrated that this ratio much higher when comparing snake predators to the snakes they prey on versus snakes and their prey.  In conclusion, venom resistance in mammals is still field with many discoveries left to be made, and some day, we may have further proof that the honey badger is the undisputed badass of the animal kingdom.

References:

1. Voss, R.S., and S.A. Jansa.  2012.  Snake-venom resistance as a mammalian trophic adaptation: lessons from didelphid marsupials. Biological Reviews 87:822-837.

2.  Begg, C.M., K.S. Begg, J.T. Du Toit, and M.G.L. Mills.  2003.  Sexual and seasonal variation in the diet and foraging behaviour of sexually dimorphic carnivore, the Honey Badger (Mellivora capensis).  The Zoological Society of London 260:301-316.

3. Voss, R.S., and S.A. Jansa. 2011.  Adaptive evolution of the venom-targeted vWF protein in opossums that eat pitvipers.  PLoS ONE 6 (6:1-9).

4. Juarez, P., I. Comas, F. Gonzalez-Candelas, and J.J. Calvete.  2008. Evolution of snake venom disintegrins by positive Darwinian selection.  Molecular Biology and Evolution 25:2391-2407.

Image References:
1.  Belinda Wright. Indian grey mongoose with dead snake prey. Retrieved from http://www.arkive.org/indian-grey-mongoose/herpestes-edwardsii/image-G52520.html
2. Colleen and Keith Begg. Scaly Feast. Retrieved from http://ngm.nationalgeographic.com/ngm/0409/feature6/zoom3.html