Small molecules, “natural products” in the lingo of organic chemists, can be widely distributed (e.g. common amino acids, coenzymes, nucleotides) or restricted to a single species. From an evolutionary perspective, the phylogenetic distribution in either case has significance. Wide distribution implies there was and continues to be strong selective advantage to making or acquiring a molecule of central importance to life. Isolated occurrence of a molecule suggests a recent evolutionary event and a specialized function. In between these extremes are molecules found in some organisms and not in others. If the organisms are closely related, the distribution is easily understood as a plesiomorphic trait arising in a common ancestor and retained by its evolutionary descendants. Most interesting and challenging, however, are molecules with discontinuous distributions that require more complicated evolutionary scenarios. Tetrodotoxin and homobatrachotoxin fall into this class.

In principle, discontinuous distributions can be explained by divergence from a distant common ancestor. However, that explanation is far from parsimonious because it requires an inordinate number of lineages to loose an advantageous trait. More reasonable are explanations based on independent acquisition or convergence. Examples in nature are well known and often share a common selective pressure. Flightless birds and insects frequently occur on islands. White animals (polar bears, arctic foxes, ptarmigans, ermine, snowy owls, etc) generally occur in the arctic. Trees appear as a growth form in many groups of plants. Certain mammals, snakes, lizards, fish, and insects are viviparous. The distributions of tetrodotoxin and of homobatrachotoxin fit this pattern.

Given that convergence (homoplasy) has occurred, there are still many evolutionary issues to address. The presence of a particular compound can be due to a new biosynthetic pathway evolved independently or acquired by genetic transformation from some other organism. It can be due to ingestion of a food containing the compound or produced by a symbiotic microorganism. Which is most likely? Have all the organisms that contain the compound used the same evolutionary strategy? Presumably, these different organisms evolved from toxin-sensitive organisms. Are there different ways to become toxin-resistant? How did the toxin-resistance evolve? Have there been mutations in the genes for the susceptible ion channels such that they no longer bind the toxin? Have binding proteins evolved to sequester, transport, or accumulate the toxins? If so, what was the function of the protein before evolving a new function?  Each of the questions in this paragraph could be the focus of a testable hypothesis and the source of a short paper to address the assignment.

Assignment: Based on your reading and group discussions, individually write a ~3 page paper discussing which hypothesis you personally favor to explain homobatrachotoxin's distribution in nature. Why do you favor it over the others? What evolutionarily biochemical adaptations might be expected? Provide a reasoned argument including relevant references to recent articles. Would you expect the story to be similar to that for tetrodotoxin?  Assume you have unlimited resources but only one year to test your hypothesis. What experiments would you do? What kinds of results would be consistent with your hypothesis and inconsistent with the others?

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