Transcriptional Rewiring in Yeast

ResearchBlogging.org

Posted by Victor Hanson-Smith.

Consider this 2006 Nature paper from Alexander Johnson’s lab. The story here is that transcriptional regulation of S. cerevisiae (i.e. yeast) mating genes has been handed-off from activation by the MATa gene to repression by the MAT-alpha gene.  This is interesting because despite significant transcriptional rewiring, the logical output (the expression of mating genes) remained the same.

First, some background on yeast. . .

Yeast are either diploid or haploid.  Both haploid and diploid cells can reproduce by mitosis, but haploid cells can sexually reproduce.  Haploid yeast are either type “a” or type “alpha.”  Type-a haploid cells can mate with type-alpha cells, and vice versa.  Haploid mating produces diploid children, which cannot themselves mate.  However, diploid children can induce meiosis (typically in response to nutritional stress) to form four haploid spores: two type-a spores and two type-alpha spores.

Type-a and type-alpha yeast cells differ in their mating pheromones.  Type-a cells produce a-factor pheromone and respond to alpha-factor; Type-alpha cells produce alpha-factor and respond to a-factor. In response to pheromone (of the opposite type) haploid yeast grow a projection called a “shmoo” towards the source of the opposite factor.

An illustration of yeast mating

Type-a cells respond to alpha-factor by using the cell surface receptor Ste2; type-alpha cells respond to a-factor pheromones using the cell surface receptor Ste3.  The interesting difference — and the focus of Tsong et al.’s paper — is that S. cerevisiae type-a mating genes are promoted by Mcm1 transcription factor, whereas C. albicans type-a mating genes are promoted by cofactors Mcm1 and MAT-a2.  Given that S. cerevisiae and C. albicans are related species, this transcriptional difference belies a rewiring event in their shared evolutionary history.

The authors identify seven type-a specific mating genes and their corresponding regulatory sequences.  Using position-specific scoring matrices and homology modeling, the authors inferred the evolutionary events that led to the hand-off between transcriptional activation and repression.  For more details, read the publication.

This paper raises several questions:

1. Did the hand-off from activation to repression incur a fitness cost?  The authors imply a binary fitness landscape: either a yeast expresses the correct mating genes or it doesn’t.  However, it seems like a more accurate fitness story would consider the energetic cost differences between the transcriptional systems used by S. cerevisiae and C. albicans.

2. The authors use C. albicans’ transcriptional phenotype as a proxy for the ancestral state.  Is this accurate?  (The answer is yes).  The alternative hypothesis, in which S. cerevisiae is the ancestral state, requires an outrageous number of gene gains and losses with respect to MAT-a2.

3. How often do these transcriptional rewiring events occur?  This question is somewhat rhetorical, because we don’t have enough information to answer it.  A naive interpretation of this paper is that the yeast MAT-a2 story is especially novel.  As we learn more about the entire transcriptional network of organisms, however, we might learn that these architectural rearrangements occur frequently.

Tsong, A., Tuch, B., Li, H., & Johnson, A. (2006). Evolution of alternative transcriptional circuits with identical logic Nature, 443 (7110), 415-420 DOI: 10.1038/nature05099

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