Show Me The Science Month Day 17

Often when something new crops up in evolutionary history, it's usually the result of tinkering with functional, preexisting molecular tools.. In a paper published in Science, some NYU researchers find that the protein cues used by  fruit fly embryos to direct their migrating reproductive cells are processed by some very ancient cellular machinery. The scientists test their ideas with a very weird experiment: they use their newfound knowledge to direct the reproductive cells to migrate into the embryos' brains.

Before we get to the ancient cellular machinery, we need to answer the most obvious question: what's up with migrating reproductive cells? These reproductive cells, technically called germ cells, are the embryonic precursors of sperm and egg cells. In a developing embryo, in both humans and fruit flies, these cells (like many cells in a developing embryo) have to migrate to their proper spot. Cells find their way by means chemical signposts: the surrounding cells help the migrating germ cells by secreting protein signals, pointing the migrants in the right direction.

The NYU researchers found that fruit fly germ cells are guided by a secreted protein that's been modified with a big, fatty tail. When the researchers deleted the gene responsible for pinning the fatty tail on the secreted protein, the germ cells lost their way. But putting the fatty tail on the protein is only part of the challenge faced by a cell: getting this modified protein across the cell membrane and out into intercellular space is hard, because the fatty tail gets in the way.

To figure out how this modified protein gets secreted from the cell, the researchers relied on a big clue found in brewer's yeast (they found the clue there because brewer's yeast has been studied so thoroughly). Brewer's yeast also secrete a protein with a big, fatty tail; this modified protein is a pheromone, which yeast use to attract a mate. To pump this pheromone out of the cell, fatty tail and all, yeast use a special transport protein. It turns out that there is a very similar protein in flies; the similarity of the fly protein to the yeast one was a dead giveaway to the scientists that this fly protein just might be the one that pumps out secreted proteins with fatty tails. And sure enough, when the researchers deleted the gene, the germ cells became confused and failed to migrate, because the guiding signal wasn't getting out.

What's even more amazing is that the scientists were able to substitute the yeast protein for the fly one; when you put the yeast pheromone pump into flies, germ cells migrate just fine. The fact that a very similar (highly conserved) protein pump is found in both yeast and flies suggests that this particular pump has been around a long time - since before the last common ancestor of yeast and flies (or fungi and animals), almost a billion years ago. A pump that was probably being used to secrete protein signals in one-celled organisms a billion years ago is now used to secrete signals that direct migrating germ cells in flies, and probably humans too (because we also have this highly conserved pump).

The NYU scientists found other fly components that strongly resembled the yeast ones, components that are involved in processing the secreted protein before it gets pumped out. This means that it's not just one protein pump that has been around a long time; the whole system for processing and secreting proteins with fatty tails is an ancient one.

The weirdest experiment of this paper doesn't have much to do with what I've been discussing above, but the experiment is a great example of what perverse things you can do when you know how to manipulate genes for a cellular process. Just to prove that they had all of the protein processing components correct, the researchers decided to see if they could get the germ cells to head way off course and migrate into the embryo brains. They took the gene responsible for adding fatty tails to the secreted protein, and they cranked it on at a high level in the embryo central nervous system. This made embryo nerve cells start secreting signals, and sure enough, the migrating germ cells headed for the brain.

Join me tomorrow, here at Adaptive Complexity, for day 18 of 30 Days of Evolution Blogging Evolution as a science is alive and well. Each day I will blog about a paper related to evolution published in 2009.

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