April 15, 2014
Imagine that your dream is to be a professional basketball player. Unfortunately for you, you are only five feet six inches tall and you can’t jump very high. No matter how much you practice and work out, it is exceedingly unlikely you will be a starter for the Miami Heat.
Now imagine instead that you are six feet tall with a reasonable vertical jump. Here, with enough effort you have a shot at beating out the guy with the genetic advantage of being six foot six inches high who doesn’t work as hard as you do. Keep practicing and you might be passing the ball to LeBron James instead of him!
In a new study in GENETICS, Frenkel and coworkers show that something similar can happen in yeast too. If a population of yeast has some overwhelming advantage over a second population, the first will quickly outcompete the second every time. But if the first population is just a bit better than the second, then the second can sometimes end up with a mutation that gives it an even better advantage than the first. Now the first population is outcompeted and the second takes over.
Of course, when presented in a general way this is sort of obvious. But Frenkel and coworkers set up their experiments in such a way that they got some hard numbers for just how much of an advantage one population needs to overcome to have a chance at winning. If six feet is tall enough, what about five feet eleven inches?
The first step was to generate a number of mutants with different measured fitness advantages. They selected mutant populations with advantages of 3, 4, 5, or 7%. These populations were all tagged with a fluorescent marker.
They then seeded these mutants individually into 658 replicate reference populations that were tagged with a different fluorescent marker. The mutants were seeded at a high enough level to prevent genetic drift from wiping them out. The authors then followed each population for hundreds of generations by determining the levels of each population every 50 or so generations.
Their first finding was that mutants with a 7% advantage won out every time. The reference population had no chance at getting a good enough mutation to beat it out. No one is going to beat LeBron James out for his starting position with the Miami Heat.
Once the advantage was only 5%, around 16% of the time the second population won out. As the advantage got smaller and smaller, the second population won out more and more often. Even a genetically less gifted player has a shot at beating out the 12th guy on the Heat’s roster!
These results can tell us quite a bit about the mutational landscape of haploid Saccharomyces cerevisiae. For example, from these data Frenkel and coworkers figured out that only populations that get mutations that give at least a 2% advantage have a chance at outcompeting other populations. By assuming a mutation rate of 4X10-3, around 1 in 1000 mutations fit this bill, which might seem surprisingly high but is consistent with previous studies. With a bit more hand waving, the authors hypothesize that disruption of something like 1 in 100 yeast genes is actually beneficial!
So yeast have a surprisingly level playing field. Unless they are up against the equivalent of Kobe Bryant or Michael Jordan, they have a good shot at stumbling on a mutation that gives them an edge over their peers.
by D. Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics
Categories: Research Spotlight