"This mating decision is controlled by a simple chemical switch that converts an incoming pheromone signal into a cellular response," says senior author Stephen Michnick, a Université de Montréal biochemistry professor and Canada Research Chair in Integrative Genomics.
"As pheromone signal increases, two enzymes in the cell begin to compete with each other, one adding, the other removing a chemical modification on a protein called Ste5," continues Dr. Michnick, noting that at a critical threshold of pheromone signal, one of the enzymes overwhelms the others' capacity to modify Ste5, triggering a sudden, switch-like cascade of chemical messages to be delivered to the cell to say it's time to mate. The findings were made in collaboration with physicist Peter Swain, of McGill University and the University of Edinburgh, and his postdoctoral fellow Vahid Shahrezaei, now a lecturer at Imperial College London, U.K. They were able to describe with mathematical precision how this switch works to drive the mating decision.
The research team used a single cell organism, i.e. yeast used to leaven bread, for their study. "Although yeast is dramatically different from people, at a molecular and cellular level we have a lot in common," says Dr. Michnick. "The same molecules that create the switching decision in yeast are found in very similar forms in human cells. Similar switching decisions to those made by yeast are made by stem cells during embryonic development and become dysfunctional in cancers."
Using yeast enabled the research to show how a cell might make important decisions. When yeast cells decide to mate, they must know that there is a mating partner close enough, and then make a snap decision to get ready to mate", says first author and graduate student Mohan Malleshaiah. Their decision to mate is not just fast, but precise, resulting in their selection of the best available partner, even though there may be many competing potential mates near by," Malleshaiah says. "Charles Darwin first discovered the principles governing how and why organisms choose mating partner 150 years ago. It is fascinating to see that the same principles that Darwin described to explain why a lioness chooses the strongest lion or a peahen chooses a peacock that has the most beautiful plumage can be so clearly observed at a molecular level in yeast," Malleshaiah adds.
Thanks to this Nature study, scientists have captured a glimpse of how cells make critical decisions about their fate. "Perhaps in the near future we may look forward to more discoveries of such switching mechanisms, with the potential of understanding and predicting how humans emerge from the complex process of cells deciding to become different tissues during development and how these decision-making switches break down in diseases," says Dr. Michnick.