Fun with yeasty beasties

I've always been quite envious of researchers who work with yeast; there are some amazing tools available for microbial genetic analysis that just don't exist for mammalian systems. You do have to put up with some unpleasant odours in your lab, but it can't be worse than the smell of baboon colon and it's usually worth it for the extra publications. I've heard that the conferences rock as well.

Trends in Genetics recently published a short paper from the University of Toronto that demonstrates the potential of yeast research. Gabriel Musso, Zhaolei Zhang and Andrew Emili analysed pairs of genes that arose when the entire genome of the Saccharomyces cerevisiae (budding yeast) species was duplicated some 100-200 million years ago. 450 pairs of duplicated genes (known as paralogs, or paralogues if you're British) still exist in the modern yeast genome.

Gene duplication is a major driver of evolutionary change. A single gene usually encodes for one specific protein that plays a particular role in the cell. Mutate that gene too drastically and the resulting protein will not be able to perform its function, which can be disastrous for the cell. Mutations in essential genes are therefore strongly discouraged, and the gene sequence is conserved by negative selective pressure. However, if a gene is duplicated and gains a paralogous “twin”, then one of the two copies is free to change and experiment with new functions, while the other is conserved and continues to perform its original function. The cell effectively acquires a back-up copy.

100 million years is obviously an extremely long time*, especially for a species that reproduces so quickly. Previous studies had suggested that paralogous yeast gene pairs have evolved for so long that they now produce proteins with quite different functions, as evidenced by their distinct interactions with different protein partners. These protein-protein interactions are incredibly important; most processes in the cell are performed not by single proteins, but rather by multiple-subunit complexes that bring together many different types of protein. Finding two paralogues in distinct protein complexes strongly implies that the two copies perform quite different functions.

Musso et al. decided to re-examine the evolutionary divergence of yeast gene paralogues using updated protein-protein interaction maps. They had at their disposal two recent Nature papers that report the most accurate and comprehensive survey yet of the repertoire of protein complexes found in budding yeast. (This is where my microbe-envy comes in). The Toronto group compared the protein-protein interactions of 158 paralogous yeast gene pairs, and also of 10,000 randomly assigned unrelated gene pairs. Contrary to previous reports, around half of all paralogue pairs were found to map to the same protein complex – a correlation more than 50 times greater than that found between the unrelated gene pairs.

Paralogous gene pairs that mapped to the same protein complex were more similar to each other in sequence than were paralogous pairs that interacted with distinct protein partners. This is a classic example of a correlation that tells us nothing about cause and effect. Does participating in the same protein complex tend to introduce selective pressures that keep the two paralogous copies more similar to one another, or do gene pairs that diverge less through evolution tend to produce proteins that interact with similar partners? The current study can not differentiate between the two possibilities, but I would intuitively favour the latter explanation. The duplicated proteins that have changed the most from the original copy are probably the ones that are out experimenting with new partners and functions, and contributing the most to evolutionary change. I'm sure that these intrepid non-identical twins will have more to tell us about evolution than will those boring old clones that still hang around with the same friends as their brothers.

*as a reference point, the last common ancestor of humans and mice is thought to have lived around 75 million years ago.