The evolution of venom: Poison pill

The bite of a rattlesnake can, within minutes, cause paralysis and extensive internal bleeding. If untreated it can kill. It might also hold the key to treating high blood pressure, heart diseases and stroke. In 1998 two drugs to prevent heart attacks, derived from rattlesnake and viper venoms, were approved. Since then a number of other venom components have proved effective against some varieties of cancer and brain disorders like Alzheimer’s or Parkinson’s, but gaining regulatory approval has proved tricky. Part of the reason is that it is difficult to tweak toxins such that they preserve their medicinal effects but lose their nefarious ones, like stanching blood flow or numbing the nervous system.

Now, though, Wolfgang Wüster, of Bangor University, in Britain, and his colleagues have stumbled on an evolutionary mechanism that might make such modifications easier in future. Dr Wüster was investigating venomous snakes and lizards to understand what they had in common. They differ in many respects—most venomous lizards, for instance, have fangs in the lower jaw, whereas snakes have them in the upper jaw. But in 2005 Bryan Fry of Sydney University found that snakes and lizards in fact share venom-making genes, suggesting that both share a venomous reptilian ancestor.

Whereas Dr Fry looked only at selected venom-making genes, Dr Wüster had the luxury of complete genetic data for different snake and lizard species. This allowed him to check if venom-spitting reptiles possess other shared genetic traits, too. As he and his team report in Nature Communications, they do.

These include genes to produce enzymes that perform some basic physiological functions. Intriguingly, some of these housekeeping genes were sitting among venom-producing ones. Venom genes are known to have evolved from more innocuous sorts, but it was thought that all the genes in a particular stretch of DNA assumed the venom-producing function. To find some that did not, therefore, posed a quandary. Were the innocuous genes among the insidious ones simply evolutionary relics? Were they evolved versions of the original innocuous genes that, unlike their venom-producing neighbours, remained innocuous? Or did they in fact evolve from venom genes that had lost their venom-producing prowess?

To help decide the matter, Dr Wüster ran a computer model to trace the genes’ evolutionary histories. This revealed that the third scenario was the most likely. Moreover, it seems that certain housekeeping genes turned into venom-producing ones and back again several times in reptiles’ genetic past. This means that the venom-producing genes and the housekeeping variety nested among them are genetically similar. As such, they produce proteins which are themselves alike in many respects, but not necessarily in their ability to do harm.

Practical applications of this knowledge are not an immediate prospect. But by understanding what makes a venom protein venomous researchers may get a better idea of how to remove the unwanted sting. That is one trick drugmakers would love to be able to pull of.

First published on

Image credit: The Economist

How does epigenetics shape life?

Identical twins, despite being biologically identical at birth, grow up to become unique individuals. Sure they may have a lot more things in common than two randomly picked individuals, yet there are many characteristics which belong only to one or the other. If the twins have the exact same DNA, then what is that makes them different?

The common answer to this question is it’s the environment that they live in which shapes them differently. Researchers have found that such environmental factors cause chemical modifications to the genome without affecting the nucleotide sequence, leading to the unique characteristics that we observe. This field of research is called epigenetics, and beyond the DNA, it’s what shapes our lives.

Rat mothers nurture their pups by licking and grooming. Researchers in Canada studying epigenetic changes found that rats whose mothers licked them more than normal expressed hundreds of genes differently from those who were licked less than normal. These differences were consistent and predictable, and led to a number of behavioural changes among the rats, including one where highly licked rats’ response to stress was a lot better than the less‐licked rats’.

Epigenetic changes don’t just occur through environmental factors but are also a different form of inheritance, one that doesn’t have to suffer from the randomness of natural selection. The licking of the rat encodes specific information onto her pup’s DNA without modifying to the sequence of base pairs. Mom’s behaviour programs the pup’s DNA in a way that will make it more likely to succeed. Such information is stored in the DNA in many ways, one of which is through DNA methylation. Through this process methyl groups are attached on to the DNA, and their attachment at specific positions leads to genes being turned on or off. This makes epigenetic changes reversible. For example, you can take a low‐nutured rat, inject its brain with a drug that removes methyl groups, and make it act like a high‐nurtured rat.

DNA methylation also plays a key role in cell division and cancer cells are known to divide faster than normal cells. Researchers in the US have developed drugs to interfere with DNA methylation as a treatment for cancer. They use molecules that mimic cytosine, one of the four bases of DNA. In cell replication, the fake cytosine swaps places with real cytosine in the growing stand of DNA, which then in turn traps DNA methyltransferase. When used in low enough doses, the drug allows the formation of the cell but with less methylated DNA. These drugs are currently being used to treat myelodysplastic syndrome, a prelukemia condition.

As Brona McVittie says, like the conductor of an orchestra controls the performance of musicians, epigenetic factors govern how the cell plays the notes in DNA. A better understanding of these factors has the potential of revolutionising evolutionary and developmental biology, thus affecting practices from medicine to agriculture.

Further reading:

  1. Learn Genetics, The University of Utah
  2. Introduction to epigenetics from Science magazine
  3. More ways to fight cancer through epigenetics, The Economist
Image credit: SciShark