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The Evolution Of Beta-defensin Peptides In Platypus Venom Gland

The evolution of beta-defensin peptides in platypus venom gland

The diagram illustrates separate gene duplications in different parts of the phylogeny for platypus venom defensin-like peptides (vDLPs), for lizard venom crotamine-like peptides (vCLPs), and for snake venom crotamines. These venom proteins have thus been co-opted from pre-existing non-toxin homologues independently in platypus and in lizards and snakes.

The sequencing of the platypus genome has received a high amount of misleading press attention. What does this information really tell us about this strangely unique animal and its genetic past?

Interpreting Shared Characteristics: The Platypus Genome

So, what are some of the details that we've learned from the platypus? One important message relates to the unity of life. Sequencing of the platypus genome reveals that the platypus has about 18,000 genes; humans, by comparison, have somewhere around 20,000. Moreover, roughly 82% of the platypus's genes are shared between monotremes, marsupials, eutherians, birds, and reptiles. This is not at all surprising, because all of these organisms are made of eukaryotic cells, and the basic eukaryotic machinery is going to be shared among species. Platypuses and humans also share a lot of "selfish" DNA bits—about half of both species' genomes consists of LINE and SINE-like sequences.

Humans and platypuses do differ in the details, however. For instance, an obvious difference is that the platypus lays yolky eggs, whereas humans and other eutherians have yolkless eggs that are retained in the mother's body. Thus, as you might expect, the platypus has a gene that humans lack—one that codes for vitellogenin, a crucial yolk protein.

As opposed to the presence of vitellogenin, a trait that both eutherians and monotremes have in common—but one that is not shared with birds—is lactation. (Although some birds can produce crop milk, this is a different adaptation). In the ancestral state, lactation was probably the secretion of fluids and immune system proteins to keep eggs and newborns hydrated and protected, but in our history, parents who invested more effort in secreting additional nutritive components, like sugars, fats, proteins, and calcium, were more successful. Like humans, the platypus secretes a true milk that is loaded with all of these components, including a protein called casein, which is thought to have originated by way of the duplication of a tooth enamel matrix protein gene, of all things. Today, two genes that code for proteins related to tooth production (enamelin and ameloblastin) are clustered with the casein-producing gene in both the platypus and the mouse, suggesting that the kind of sophisticated lactation abilities shared by monotremes and eutherians arose prior to the Jurassic period.

One particularly interesting specialization in the platypus is the evolution of venoms. The platypus has small, sharp spurs on its hind limbs that it uses to inject defensive poisons into predators, an unusual feature not found in other mammals. Where did these venoms come from? As it turns out, they arose through the duplication of genes that have other functions, with subsequent divergence. Many of these genes are involved in the functioning of the platypus's innate immune system. In particular, there is a set of genes in the platypus that code for the production of proteins called b-defensins. These are small, cysteine-rich peptides that are rather like the "bullets" of the immune system; they can bind to viral coat proteins and punch holes in bacterial membranes. We humans have many epithelial cells that secrete b-defensins onto our skin and the lining of our gut and respiratory tract to kill invaders. The cells of our immune system also spew these proteins onto foreign and phagocytized cells to kill them. The platypus has repurposed the b-defensin genes, making copies that have been selected for more effective toxicity when their product proteins are injected into other animals. One especially interesting observation is that these are the same proteins used in venomous reptiles—for instance, snake venoms also contain novel forms of b-defensins. This means that animals from two distantly related groups—the lepidosaurs and the monotremes—both use b-defensin-derived venoms (Figure 2). But does this imply that the groups' last common ancestor also used these venoms?

No, it does not, and here's why: It turns out that venomous snakes and the platypus have different duplications of the b-defensin genes. So, while co-opting these genes seems to be a common strategy for evolving venoms, the details of the gene duplications reveal that platypus venom and snake venom are independently derived features. The production of venom in these animals is therefore clearly a case of convergent evolution.

Five Surprisingly Venomous Animals

Venom is usually associated with insect stings and reptile bites.

But this versatile, injectable substance is also used to attack or defend by a number of animals - including some you might not expect.

Slow lorises (above) are the only venomous primates. They have become an internet sensation thanks to videos of them raising their arms to be 'tickled'. However, a slow loris with its arms raised is actually taking a defensive posture.

The primate raises its arms for easy access to the toxin-producing brachial gland under its arm. The animal licks the gland, because mixing the toxin with saliva is how its bite becomes venomous.  

Sadly, the slow loris is frequently illegally traded, sold across the world as an exotic pet.

To avoid a bite that can lead to anaphylaxis and death in humans, traders often clip the animal's teeth. Many slow lorises die as a result of blood loss or infection from these procedures.

Another remarkable thing about this primate is its colouration. It is thought that the patterns on its fur developed to mimic the colouration of cobras, helping it to prevent predator attacks.

Platypus

Only the male platypus produces venom, which is sometimes used for defence, but mostly for fighting over both territory and females during the mating season © worldswildlifewonders/ Shutterstock

The platypus is one of only five species of egg-laying mammals, known as monotremes. All monotremes are native to Australia and New Guinea.

The platypus has a range of features that make it quite unlike any other animal.

With a large bill, a paddle-like tail, webbed feet and a furry body, this funny-looking animal produces venom that evolved to cause pain, mainly in other platypuses.

Male platypuses possess a sharp set of spurs on their hind heels and use their venom against other males to maintain their territory. The venom is produced seasonally, increasing in the mating season.

Humans who have been envenomed by a platypus experience excruciating pain that, while non-fatal, also can't be eased by traditional painkillers like morphine.

Mosquito

In response to a mosquito bite, the human body produces histamines, causing a red welt. This compound is the immune system's response to a foreign pathogen entering the bloodstream. © James Gathany, CDC/ Wikimedia Commons

Female mosquitoes feed on blood through a needle-thin and straw-like proboscis, although the resulting itchy red lump on the skin is referred to as a bite.

The mosquito pierces the skin and searches for a blood vessel, then injects saliva into the wound. Full of anti-coagulants, the saliva prevents the wound from closing, allowing the insect to drink its fill.

As an injectable substance, mosquito saliva can be considered a type of venom.

However, the red lump isn't caused by the venom but the human body's response to it. To fight the saliva, the body produces histamines that cause the blood vessels in the affected area to swell, resulting in the lump.

Mosquito venom may not be particularly dangerous, but the diseases these insects can harbour often are.

Malaria kills 600,000 people every year, and an additional 12,000 deaths are caused by yellow fever. Mosquitoes can also carry dengue and Japanese encephalitis among many other diseases.

Shrew

Mainly feeding on insects and earthworms, shrews don't have to use their venom to overpower their prey. Instead they use it as a natural food preservative. © Gilles Gonthier/ Wikimedia Commons

Shrews are small, mole-like mammals that are sometimes mistaken for mice. But unlike most other mammals, some shrew species are venomous. One of these is the American short-tailed shrew (Blarina brevicauda).

Venom can be transferred in many ways, including through spines, stingers or claws.

Unlike many venomous animals' teeth, which are hollow, shrews' teeth feature a groove along their sides, acting as a channel for the venom's delivery.

Shrews are thought to mainly use their venom for immobilising the small insects and earthworms they prey on.

In this instance, venom is a kind of preservative.  The prey are paralysed and stored in the shrew's burrow. Paralysing the prey - as opposed to simply killing it - keeps food fresher for longer, after all.

Shrews eat at least their own body weight in food each day. Without the ability to store food this would be difficult for the mammal to achieve, especially in winter when supplies are scarce.

Cone snails

Despite their modest appearance, cone snails produce venom that is exceptionally potent, with that of one species being strong enough to kill humans © Laura Dinraths/ Shutterstock

Cone snails are a group of predatory sea snails. With colourful shells, these molluscs come in a variety of sizes and feed mainly on worms, although some have evolved to feed mainly on fish.

Their elegant appearance belies a remarkably effective hunting technique. Cone snails have a hypodermic needle-like tooth to inject their prey with paralysing venom. The tooth is launched like a harpoon, latching onto the unlucky victim. Some species are even equipped with a backwards-facing barb.

Their venom is a cocktail of toxins that paralyses their prey.

But the geography cone (Conus geographus) first disperses its toxins through the water. This is absorbed through the gills of its prey, causing them to become disorientated and enter a state of hypoglycaemic shock.

Then the cone harpoons the prey, leaving the fish to struggle for only one or two seconds before it is paralysed.

The venom of the fish-hunting geography cone is potent enough to kill humans, making this unassuming-looking mollusc one of the most venomous animals on Earth.

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