Spider and centipede venom evolved from insulin-like hormone
Funnel-web spider venom contains powerful neurotoxins that instantly paralyze prey (usually insects). Millions of years ago, however, this potent poison was just a hormone that helped ancestors of these spiders regulate sugar metabolism, similar to the role of insulin in humans. Surprisingly, this hormone's weaponization--described on June 11 in the journal Structure--occurred in arachnids as well as centipedes, but in different ways.
Researchers at the University of Queensland in Australia and Lewis & Clark College in Portland, Oregon, made the connection while screening for similarities between the venom proteins and other molecules. They found that even though the toxins and the hormone had different genetic sequences, they had similar molecular shapes.
"If you take the sequence of the spider toxin and you do a BLAST search, the hormone is so different now that you don't pull it out," said study senior author Glenn King, a biochemist and structural biologist at the University of Queensland's Institute for Molecular Bioscience. "But when we did a structural search and it pulled up the hormone, that's what really surprised us--the sequence didn't tell us where the toxins evolved from, but the structure did pretty clearly."
Knowing a toxin's past is useful for the development of new pharmaceuticals and bioinsecticides. Venom molecules are extremely complex (some are made up of over 3,000 peptides), so once the structure is known, researchers such as King can more easily "evolve" a toxin by making changes to its sequence to add or remove functions. The products of such experiments have yielded blood pressure drugs, analgesics, and bioinsecticides--all organically based and so naturally break down.
King's group found that centipede venom has more subtle alterations of the hormone that make it more stable and therefore a better engineering template. He is collaborating with biological and chemical engineer Jennifer Cochran at Stanford University to conduct these in vitro evolution experiments on the spider and centipede toxins. The goal is to take away their toxicity and find opportunities to use them to solve agricultural or medical problems.
One question that remains is how a body protein evolved into a weapon. King hypothesizes that the hormone may have been recruited into an ancient arthropod's venom to cause adverse effects in prey. "If a hormone does something bad to prey, you might recruit it into the venom and make lots of it," he says. "That's the starting point and it can then evolve to become more potent."
In an example of convergent evolution, centipedes and spider neurotoxins used different strategies to turn the hormone into a potent neurotoxin. Both arthropods also have multiple versions of the venom molecules; a sign that they have been successful enough for new functions to be added on over evolutionary time.
Source: Cell Press
Molecular & Cell Biology
-
Human kidney progenitors isolated, offering new clues to cell renewal
-
Scientists uncover the way a common cell enzyme alerts the body to invading bacteria
-
Calcium channel blockers caught in the act at atomic level
-
Genetic regulation of the thymus function identified
-
Nobel laureate, new technologies show how cancer cells protect chromosomes from decay
-
A molecular alarm clock awakens resting ovules
-
Neuron unites 2 theoretical models on motion detection
-
Scientific serendipity yields new neuron type in mouse retina
-
Researchers find how proteins control gene expression by binding both DNA and RNA
-
TSRI researchers find 'lead actors' in immune cell development
-
UMD researchers discover a way that animals keep their cells identical
-
Cell death: How a protein drives immune cells to suicide
-
Viruses revealed to be a major driver of human evolution
-
Open chromatin profiling key to identifying leukemia cells of origin
-
The importance of keeping silent...in breast cancer cells