New & Noteworthy

Yeast, Place your Bets

May 25, 2012

Life is a balancing act.  An organism needs to grow and divide as fast as possible in its current environment.  But it also needs to be able to survive when the environment changes.

One way nature has come up with to deal with this balancing act is called bet hedging.  Basically some members in a population grow well in one set of circumstances and another set grows well in another.

Now this makes obvious sense when looking at members of a species that vary genetically.  Where it gets interesting is when bet hedging happens in a clonal population.

The idea is that even though they share the same DNA, there are epigenetic differences that cause subtle variations in gene expression levels between individuals.  These differences in gene expression patterns result in altered survival rates under different circumstances.

This phenomenon has been difficult to study because researchers need to focus on individuals and not populations.  Growth curves in liter flasks are of little use.

But now Levy and coworkers have come up with a new high throughput assay that allows them to look at how a few individuals are growing.  This has allowed them to quantitate how different individuals grow in a population and why the slower growers and/or the elderly are better able to survive stress.

The assay uses time-lapse bright-field microscopy to look at tens of thousands of microcolonies all at once.  What they find is a wide range of growth rates.  Somewhere between 1.3-10% of microcolonies grow at less than half the rate of the population as a whole (the number depends on the strain). 

The researchers identified multiple genes that impacted the range of growth rates within a population without necessarily affecting the overall growth rate.  In other words, this phenomenon isn’t simply due to chance–there are key genetic factors that help determine the amount of individual to individual variation in a population.

Levy and coworkers focused on Tsl1p, a component of the trimeric complex that synthesizes trehalose.  What they found was that those cells that made more Tsl1p divided less often and so grew more slowly.  Remember again, this is in a clonal population.

Trehalose is thought to help preserve proper protein folding under stress.  So the idea is that some subset of individuals is primed for stress but that in turn, this preparation makes them grow more slowly.  And this is just what the researchers found.

When they subjected colonies to heat stress, those that made lots of trehalose were more likely to survive.  But the survivors didn’t stay slow growing for long.  After multiple generations, the population returned to the original growth rate with the original individual to individual variation.  The phenotype was reversible.

Finally the researchers discovered that older yeast cells tended to make more trehalose and so survived stress better.  It may be that as a yeast cell gets older, it makes more Tsl1p which helps to set up the range of growth rates among individuals.  This may be one way individual to individual variation has evolved in yeast.

Bet hedging is obviously a great way to ensure the survival of a clonal population. Under ideal conditions, the fast growers can grow like mad, spreading themselves far and wide.  But when conditions become more hostile, a few slower, tougher individuals can survive to keep the population alive.

Video showing that slow growers survive heat shock and then revert to fast growers.

by D. Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics