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(l to r) Andrew Murray and Lori Huberman

What makes a sex?

There are two answers to this question, the master regulators that tell organisms which sex they should be and the downstream genes that encode the molecules that make sexual behavior possible. Answering these questions is easier in the brewer’s yeast, Saccharomyces cerevisiae, where there are two mating types, called a and alpha, and single, haploid cells mate with each other by growing towards each other, touching at their tips, and then fusing to form a single, diploid cell. Genetic analysis in yeast identified the master regulators many years ago, and produced a list of candidates for the downstream genes. Chief among these were the pheromones that the two mating types secrete and the pheromone receptors that detect and respond to the pheromones. But are these the only genes needed for mating and how carefully do cells have to control their expression to get mating to be efficient?

Lori Huberman, a graduate student in the Murray lab, set out to answer these questions by genetic engineering. She started by making “transvestite” cells that swap the pheromone, pheromone receptor, and pheromone processing factors of one mating type for another.  If these are the only genes that matter, two transvestites should mate with each other just as efficiently as two wild type cells. Instead, Lori found that the transvestites mate with each other almost a thousand times less well than pairs of wild-type cells.

This finding prompted her to look for additional factors involved in efficient mating and she found two. The first was a novel protein found in ? cells, which she called Afb1 (afactor barrier) because it interferes with the pheromone secreted by a cells. We presume that the normal role of Afb1 is to keep ? cells from being overstimulated when they find themselves in dense mating mixtures with many a cells, all producing pheromone. The second requirement for efficient is making enough pheromone. Transvestites make about a tenth as much pheromone as wild-type cells and mate worse, even when the two mating partners are one transvestite and the appropriate wild-type cell. Artificially increasing pheromone production in the transvestite increases its mating efficiency to almost wild type levels.

The finding that varying the level of pheromone production affects mating efficiency has an evolutionary connection. If an organism wants to pass on its genes as efficiently as possible, it should mate with a partner who has excellent genes. One way of advertising that you have great genes is to succeed in doing something that takes time and energy, like growing very big antlers if you’re a deer, or making a ton of pheromone if you’re a yeast cell.  Supporting this notion, Lee Hartwell and his colleagues showed that yeast cells pick the partner who makes  more pheromone, which in turn implies that the efficiency of mating should depend on how much pheromone cells make. Thus, for yeast, the price of the competition that leads to evolving better sexual advertising can be to make the effectiveness of mating very sensitive to exactly how much pheromone a cell produces.
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