Finding platypus venom

Platypuses^[1] are one of Australia’s oddest creatures.

They’re furry, mainly nocturnal aquatic creatures that swim with their eyes shut paddling with their webbed front feet and steering (or braking) with their rear feet. Their homes are burrows in the river banks. While not endangered, water pollution is an issue for their survival.^[2]

Platypuses are monotremes, best known as mammals that lay eggs.^[3] Their duck bill-like snout is famous world-wide. Important for our story, males squirt venom from a venom gland through a spur on their hind legs.

Toxins and venoms have useful medical applications. They are molecules that have powerful biological effects in small amounts.

As an hypothetical example,^[4] consider one way evolution might result in a (snake) venom molecule that induces heart attacks in victims. An ancestral form of the animal had a gene that coded for a very short protein, a peptide, used to control it’s own heart. Imagine now the gene coding for that peptide duplicating, to create a second copy. If the second copy is active in the venom gland, the peptide can act on the animal’s attacker or victim. Over time, the gene may adapt so that the second copy is only active in the venom gland. It’s now free to evolve to become more potent without affecting the animal it’s from. A new venom-encoding gene has evolved. Careful use of it might be valuable for controlling the heart in medical applications.

Thus, we can imagine (some) venoms as modified regulatory molecules that have become particularly potent in their effect.

There is a limited supply of platypus venom, and only a few venom peptides have been fully identified so far.^[5]

Rather than battle this head-on using a more traditional approach of collecting venom samples and identifying what in them are toxic, an Australian group lead by Wesley Warren collected the genes that are expressed in the venom gland and worked from them.

Since these venomous peptides are coded in genes, they reasoned they could collect all the active genes from the venom gland tissue of an in-season male platypus, then compare the genes being expressed there with those known to code for venomous peptides in other species they might identify more of the remaining platypus venomous peptides.

Genes code for RNA molecules, mRNAs, that are translated into proteins. DNA is usually found as two strands, each complementing the other. Given a single strand of linear RNA, such as mRNA, researchers can enzymatically make a complementary DNA strand.

(The enzyme used, RNA reverse transcriptase, is the same used by RNA viruses to make a DNA copy of their RNA genome to insert into their host species.)

These complementary DNAs, cDNAs, can be inserted in small independent genomes (plasmid genomes) to be added to bacteria that are grown to create larger amounts of the cDNA that are sequenced.

The sequenced cDNAs, usually short compared to the full-length genes, are compared to the genome of the animal they came from to identify the genes the cDNAs are from.

You can see how this work builds on the recently sequenced platypus genome, by using it to identify the genes the shorter cDNAs come from, and how the genome sequence of an odd animal like the platypus might help work towards medical uses.

Comparing^[6] the genes the cDNAs indicate are expressed in platypus venom glands to databases of known toxin proteins (the Tox-Prot database), they found 83 new candidate venom genes, which will now be studied more closely.^[7]

Aside from that platypuses are interesting little animals, and that venom is interesting too, my interest is that this work in part depends on my field, bioinformatics, at many different points. (Too many to bore you with here.) One challenge for the bioinformatics is that there are no genomes for species closely related to platypus.^[6]

Their results show that very divergent species – platypus, reptiles fish, even insects – share some venom proteins, suggesting that particular proteins are repeatedly uncovered in evolution as being toxic.

Because their work relies on comparing with known toxin proteins, it will miss ones that are unique to platypus.

Footnotes

Factoid: While some sources claim young platypi are called puggles, this is disputed elsewhere, claiming their is no established name for their young.

1. Below is a short list of resources describing platypuses:

• http://australian-animals.net/plat.htm
• http://www.australianfauna.com/platypus.php
• http://rainforest-australia.com/Platypus_page_2.htm
• http://www.expasy.org/spotlight/back_issues/sptlt029.shtml

2. Recent local news from Melbourne reports the return of a platypus to city areas of a river.

3. Based on an article at Evolution Bites.

4. While best known for laying eggs, the term monotreme is because these creatures have their urinary, defecatory, and reproductive systems all opening into a single duct. (Mono = one; treme = hole.) They do lactate, but have no nipples, oozing milk via glands close to the surface of patches of the skin. They also feature electro-location (via receptors on the snout in the case of platypuses) and lack a corpus callosum, the nervous tissue that connects the two hemispheres of the brain in placental mammals.

5. 19 fractions have been identified, but only three peptides fully sequenced according to Whittington et al.

6. Being a nit-picky computational biologist, I wonder if more sophisticated (and sensitive) approaches for the comparisons might yield more findings. But then, I’m sitting on the sidelines, fidgeting.

7. As this is an initial screen of the venom genes, they go on to present each found, what kind of gene it is and how it might act. I’ve left this out. Way too much for a blog article.

(Updated to add tags. And again to add Research Blogging ‘Editor’s Selection’ badge.)

References

Whittington, C., Papenfuss, A., Locke, D., Mardis, E., Wilson, R., Abubucker, S., Mitreva, M., Wong, E., Hsu, A., Kuchel, P., Belov, K., & Warren, W. (2010). Novel venom gene discovery in the platypus Genome Biology, 11 (9) DOI: 10.1186/gb-2010-11-9-r95

Warren WC, Hillier LW, Marshall Graves JA, Birney E, Ponting CP, Grützner F, Belov K, Miller W, Clarke L, Chinwalla AT, Yang SP, Heger A, Locke DP, Miethke P, Waters PD, Veyrunes F, Fulton L, Fulton B, Graves T, Wallis J, Puente XS, López-Otín C, Ordóñez GR, Eichler EE, Chen L, Cheng Z, Deakin JE, Alsop A, Thompson K, Kirby P, Papenfuss AT, Wakefield MJ, Olender T, Lancet D, Huttley GA, Smit AF, Pask A, Temple-Smith P, Batzer MA, Walker JA, Konkel MK, Harris RS, Whittington CM, Wong ES, Gemmell NJ, Buschiazzo E, Vargas Jentzsch IM, Merkel A, Schmitz J, Zemann A, Churakov G, Kriegs JO, Brosius J, Murchison EP, Sachidanandam R, Smith C, Hannon GJ, Tsend-Ayush E, McMillan D, Attenborough R, Rens W, Ferguson-Smith M, Lefèvre CM, Sharp JA, Nicholas KR, Ray DA, Kube M, Reinhardt R, Pringle TH, Taylor J, Jones RC, Nixon B, Dacheux JL, Niwa H, Sekita Y, Huang X, Stark A, Kheradpour P, Kellis M, Flicek P, Chen Y, Webber C, Hardison R, Nelson J, Hallsworth-Pepin K, Delehaunty K, Markovic C, Minx P, Feng Y, Kremitzki C, Mitreva M, Glasscock J, Wylie T, Wohldmann P, Thiru P, Nhan MN, Pohl CS, Smith SM, Hou S, Nefedov M, de Jong PJ, Renfree MB, Mardis ER, & Wilson RK (2008). Genome analysis of the platypus reveals unique signatures of evolution. Nature, 453 (7192), 175-83 PMID: 18464734

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