New & Noteworthy

When One Spark Isn’t Enough

August 7, 2013

A single mutation, just like a single spark, is more likely to fizzle out.

As anyone who has ever tried to start a fire with flint knows, a single spark is rarely enough.  You need to get a bunch of sparks all working at once to end up with that roaring campfire.  And with the wrong kindling or wood, even lots of powerful sparks just can’t get it done.

A new study in the yeast S. cerevisiae by Lang and coworkers suggests that evolution may be similar.  A single helpful DNA change may not be enough to give an individual yeast that leg up it needs to spread through the population.  Turns out that more often than not it needs something like 5-7 mutations.   And again, even that may not be enough if the rest of its DNA isn’t up to par.  A set of powerful sparks on soggy wood still won’t light a fire.

Lang and coworkers followed 40 different yeast populations for a thousand generations as the yeast adapted to a new environment (rich medium).  They sequenced each population to 100-fold depth at 12 different time points.  Not only did this allow the researchers to watch mutations rise and fall over time, it also let them screen out sequencing errors.  Real mutations will correlate over time, sequencing errors won’t.

The key finding of their research was that mutations that increased in the population over time almost always came in bunches (or cohorts) and that not all the mutations were beneficial.  Neutral mutations invariably hitchhiked along with strongly beneficial ones.

A great example of this involves the ELO1 and GAS1 genes.  These two mutations arose together in a yeast population but when the researchers looked at each individually, only GAS1 was beneficial.  ELO1 appeared to go along for the ride.

Another key point of this study is that mutations do not happen in a vacuum…beneficial mutations only “catch” in the context of a good background.  This is clearly shown in one of the populations they followed. 

In this population, yeast with a mutation in the SPC3 gene began to spread through the population.  After about 300 generations, though, a second yeast with mutations in the WHI2 and ROT2 genes began to outcompete the SPC3 mutant.  If things stayed like this, the SPC3 mutation would disappear from the population even though it was obviously helpful.

What happened instead was that a yeast with the SPC3 mutation developed a useful mutation in the YUR1 gene.  This combination was strong enough for this yeast to stay in the game until one of them developed a third mutation in the WHI2 gene.  This triple threat proved too much for the yeast with the mutations in the WHI2 and ROT2 genes – they were driven to extinction.

No wonder people refer to evolution as a dynamic process!  This example shows just how tumultuous it actually is.  Even helpful mutations like the ones in ROT2 and WHI2 can disappear over time if they happen in a weaker background.  And presumably even potentially harmful mutations can spread if they hitchhike along with a cohort of strongly beneficial mutations.

These results not only shed light on how evolution works, but could also spark other discoveries on how cancer progresses, how bacteria become resistant to antibiotics, and how viruses deal with our immune system, just to name three.  And that could help kindle a brighter future.  

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