Platypus venom- weird and unique, as expected

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“Do you think God gets stoned? I think so — look at the platypus.”

-Robin Williams

Venom isn’t very special in the animal kingdom, but our anthropocentric mindsets tend to focus more on large mammals than anything else, so to us it seems pretty mystical. Only a dozen or so mammals deliver venom, almost all of which deliver it via a bite for defense or predation. The platypus is unique in that it is so far the only animal known to use venom for a purpose other than defense or predation.

Only the male platypus has venom. And the male platypus only seems to have potent venom seasonally. The season when they have a lot of venom is unsurprisingly mating season, as the males actually use their venom, injected via venomous spurs on their hind legs, for intraspecific competition with other platypus males to keep territories and mates. While technically the echidna has venom, it can’t erect it’s spurs, and simply excretes a milky secretion.

platypus-spur-png.pngTheir venom, though nonlethal, causes excruciating pain for hours or days and is essentially nonresponsive to morphine. Only nerve-blocking agents (or antivenom) can provide relief.

A 2010 study found 83 peptides in platypus venom, many of which resemble venom genes from snakes, sea stars, and spiders. The platypus and reptiles have independently co-opted the same genes for venom usage making the platypus venom a cool example of molecular convergent evolution.

And just so the monotremes can continue to follow their pattern of general nonconformity and being surprisingly different from each other, the echidna venom gland transcriptome looks very different from the platypus one. You can read this post on their weird sex chromosomes for more.

The venom induces Ca2+ influx in cells, which results in neurotransmitter release. Defensin-Like peptides (defensins being immune proteins that usually defend the host from microbes), C-type natriuretic peptides (OvCNPs), nerve growth factor (OvNGF), and hyaluronidase have also been found. These peptides cause muscle relaxation, inflammation by promoting histamine release, and form ion channels in the lipid membranes of cells. The venom also contains a D-amino acid (as opposed to just all L-amino acids, which is the isomer previously thought to be the only conformation manufactured by cells).

First venomous animals were mammals
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Artist interpretation of Euchambersia mirabilis

The platypus having venom and laying eggs isn’t even that weird, as it seems to be that that was the norm for the ancestors of mammals. Euchambersia mirabilis, a therocephalian therapsid from the end of the Permian (~255 mya), which were some of the “almost-mammals” (the term “mammal-like reptile” is horribly outdated and silly but for some reason people still use it), was determined to have venom glands. Venom glands which appeared way before snakes and lizards evolved them, and actually millions of years before any snakes even existed.

bk9781849736633-00001-f1_hi-resSo while venom in mammals is very rare now, it may actually be an ancestral characteristic. Venom relatively expensive to have as it requires some method of injection into another animal, a gland, and then the making of proteins. It’s also suspected to be expensive because the loss of venom in animals that are no longer under pressure to produce any, is very common. Venom has a weak phylogenetic signal—similar types of venom are not necessarily found near each other on a phylogenetic tree, so genetically it seems not very “difficult” for various venoms to arise.

Monotreme venom as diabetes treatment?

The hormone, glucagon-like peptide-1 (GLP-1), is secreted in the gut, stimulating the release of insulin to lower blood glucose. But GLP-1 typically degrades within minutes in humans.

People with type 2 diabetes can’t maintain a normal blood sugar balance, but maybe they could if they had a less rapidly degrading GLP-1.

However in the platypus, there’s conflicting functions of the GLP-1. Not only is it a regulator of blood glucose in the gut, it is also in their venom. This conflict between the two different functions has resulted in the evolution of a dramatically changed GLP-1 system. GLP-1 in monotremes is resistant to the rapid degradation that occurs in other animals, and degrades by a completely different mechanism.

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GLP-1 and diabetes relationship

The function of GLP-1 in the venom seems to have resulted in the evolution of a stable form of GLP-1 in monotremes. Stable GLP-1 molecules can potentially be used as a type 2 diabetes treatment.

Both platypus and echidnas have evolved the same long-lasting form of the hormone GLP-1 despite echidnas not having spurs.

 

Sources:

  1. Kita, Masaki, David Stc. Black, Osamu Ohno, Kaoru Yamada, Hideo Kigoshi, and Daisuke Uemura. “Duck-Billed Platypus Venom Peptides Induce Ca2 Influx in Neuroblastoma Cells.” Journal of the American Chemical Society50 (2009)
  2. Enkhjargal Tsend-Ayush, Chuan He, Mark A. Myers, Sof Andrikopoulos, Nicole Wong, Patrick M. Sexton, Denise Wootten, Briony E. Forbes, Frank Grutzner. Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions. Scientific Reports, 2016
  3. Julien Benoit, Luke A. Norton, Paul R. Manger, Bruce S. Rubidge. Reappraisal of the envenoming capacity of Euchambersia mirabilis (Therapsida, Therocephalia) using μCT-scanning techniques. PLOS ONE, 2017

Sex determination in monotremes- way weirder than the whole laying eggs thing

baby-platypus

Sex determination and sex chromosome evolution is a lot less well-understood than most people would probably assume. One of the most puzzling cases is that of the platypus and echidna, the only members left of a group of mammals that diverged from theria about 210 million years ago.

Way more than just two

The platypus has 10 sex chromosomes, while the echidna has nine. Sex determination occurs by the sex chromosomes aligning during male meiosis as X1Y1X2Y2X3Y3X4Y4X5Y5, so five X chromosomes go into one sperm cell, and five Y chromosomes go into another. What happens if the chromosomes align “incorrectly” is entirely unknown, and considering how understudied monotremes are, unlikely that we’d get to see any examples (but I’d imagine one could learn a lot about their sex-determination from that).

No SRY or DMRT1

In placental mammals and marsupials, the SRY gene on the Y chromosome is what determines sex, as it controls the formation of testes.

Birds however, have a ZZ/ZW system where the females are actually the heterogamateic sex having a Z and a W sex chromosome. Sex determination in birds is controlled in a dosage-dependent manner where the females only have one copy of the DMRT1 gene, while the males, being ZZ have two copies.

What’s really interesting though, is that the SRY gene is absent in monotremes and very few genes have actually been identified on the Y. One gene suspected to play a role in sex determination is Y chromosome gene, anti-Müllerian hormone, Amhy, though the molecular bases actually determining sex in monotremes is still not known.

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Weird Homology

Platypus X1Y1X2Y2X3 are homologous to echidna X1Y1X2Y2X3, however the platypus X5 is homologous to echidna X4, platypus Y5 is homologous to echidna Y3, and platypus X4 and Y3 homologs are in echidna autosome 27 whereas echidna X5 and Y4 are in autosomal platypus chromosomes.

Genes found on the therian X chromosome are orthologous to platypus chromosome 6, the homolog of echidna autosome 16. SOX3, thought to be the sort of “X-version of SRY” is autosomal in monotremes, as well as other non-therian vertebrates. SRY is probably a derived trait that only evolved after the divergence of monotremes from other mammals.

That being said, no homology has been shown so far between any platypus X chromosomes and therian X. Monotremes XY chromosomes are unique but show some homology with bird chromosomes, which is especially interesting considering in birds sex-determination works very differently from mammals and females are the heterogametic sex.

Whether sex-determination works in monotremes as a dosage-dependent set up (like in birds), or in a Y-gene set up as seen in humans, is still unknown.

Monotremes are relatively ignored because there’s just not very of them, but for an evolutionary biologist they can be very useful in trying to answer questions related to amniotic lineages and divergence. While still mammals, they are genetically very distant from other mammals, even though people tend to maybe think of marsupials and monotremes as being more similar (both Australian, both not placentals), monotremes are a real anomaly.

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sources:

  1. Diego Cortez, Ray Marin, Deborah Toledo-Flores, Laure Froidevaux, Angélica Liechti, Paul D. Waters, Frank Grützner, Henrik Kaessmann. Origins and functional evolution of Y chromosomes across mammalsNature, 2014
  2. Grützner F., et alNature,  doi:10.1038/nature03021 (2004).
  3. Sex determination in platypus and echidna: autosomal location of SOX3 confirms the absence of SRY from monotremes. M. Wallis-P. Waters-M. Delbridge-P. Kirby-A. Pask-F. Grützner-W. Rens-M. Ferguson-Smith-J. Graves – Chromosome Research – 2007