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Smoothing Over an Extra Chromosome

August 22, 2013

Let’s say you had a rock you had to move that was way too heavy for you to lift. You could either start lifting weights until you could move it yourself or get someone to help you. Most of us would start texting our friends pretty quick.

Jon Bon Jovi used scissors to go from fluffy to smooth. Yeast uses an extra chromosome XVI.

Turns out our friend S. cerevisiae can be the same way. Many strains of this yeast can exist as either a fluffy colony or a smooth one. In a new study, Tan and coworkers show that some of these strains switch between the two by gaining or losing one of their chromosomes. They’d rather “get” an extra chromosome than try to gain a mutation that activates the necessary gene(s).

In this study, the authors found a strain where around one in a thousand yeast switched between fluffy and smooth colonies. As the smooth colonies grew, they developed “blebs” – little bumps on the smooth colonies.  Turns out these were yeast that switched back to the fluffy morphology.  The authors set out to explore why this strain switches at such a high rate and why it would want to. 

A first look showed that when this yeast strain went from fluffy to smooth, it gained an extra copy of chromosome XVI.  When the new smoother yeast lost this extra chromosome, it reverted back to its fluffy look.  A harder look showed that an extra chromosome XVI wasn’t the only way to a smoother yeast.  Occasionally the fluffy to smooth change could be caused by an extra copy of chromosome III, X, or XV, and an extra copy of V caused a slightly smoother colony.

These results suggest a couple of different ways that an extra chromosome might be leading to a smooth colony.  One is that just having extra DNA around causes the change.  The other is that a variety of genes can cause the change when present in higher than normal doses.  The researchers show pretty convincingly that the second reason is probably the right mechanism.

First off they show that not all extra chromosomes are created equal.  Some lead to a very sickly yeast while others have no effect on fluffiness.  Just having extra DNA around is probably not the culprit.

The authors next set out to figure out exactly what was going on with chromosome XVI.  Through a series of deletion studies, they found a single gene responsible for the fluffy to smooth shift – DIG1.  Overexpression of this single gene caused fluffy colonies to turn smooth.  Presumably there are other genes on some of the other chromosomes that serve a similar function.

They next set out to determine why yeast would ever want to do this.  Turns out that, as you might expect, each phenotype has an advantage in a different situation.  On a solid surface the fluffy strain did better, while the smooth one did better in liquid media.  

The “extra chromosome option” is actually a great way for a sedentary beast like yeast to quickly deal with a new situation.  Gaining an extra chromosome is much simpler than gaining a new mutation that up-regulates a gene under certain situations.

Figuring out this mechanism of fluffy to smooth transitions isn’t just fun biology either.  It may also point us in new directions for treatments for a variety of diseases, including drug-resistant cancers and microbial infections. 

In many cases, these cells become resistant because their chromosome number has changed from what is considered the norm.  If we could find a way to force cells to maintain the correct number of chromosomes, we might be able to make them more susceptible to drugs.  As usual, yeast studies are much more than fluff…they smooth the way to the future.

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