Genetic defects can provide a long-term evolutionary advantage

Evolution seems to be a story of continual progress. The weak will perish, according to Darwin’s law. Nevertheless, genetic defects that at first glance might make an organism weaker can increase its long-term chances of survival. At first sight, evolution seems to be a story of continual, step-by-step progress. The weak will perish, according to Darwin’s law of survival of the fittest. Nevertheless, genetic defects that at first glance might make an organism weaker can increase its long-term chances of survival. These noteworthy findings from bioengineers at KU Leuven and the Flemish Institute for Biotechnology mark an important step in our understanding of evolution.

In order to study evolutionary processes, you need a good research model. Because human beings take years to reproduce, researchers turn to other organisms, such as yeast. Yeasts are single-celled organisms that divide approximately every 1.5 hours, meaning that only a few weeks are needed to cultivate hundreds of generations.

To our surprise, after a few weeks the majority of these damaged strains were actually growing faster than the strains in which we disabled no genes. Therefore, at the end of the journey, they are better developed and reproduce more quickly.

Jana Helsen (Centre of Microbial and Plant Genetics) cultivated a range of yeast strains for her PhD research to mimic evolution in the lab. “On the one hand we used normal, ‘healthy’ yeasts, while disabling a single gene in other strains. So these strains, each of which bore a genetic defect, actually started the race with a handicap. To our surprise, after a few weeks the majority of these damaged strains were actually growing faster than the strains in which we disabled no genes. At the end of the journey, then, they are better developed and reproduce more quickly.”

Hill or Mount Everest

The findings demonstrate that evolution is not just a story of continual improvement. “You can view evolutionary biology as a landscape with hills and mountains of differing heights,” explains professor Kevin Verstrepen (KU Leuven and the Flemish Institute for Biotechnology). “Darwin’s theory holds that all living beings are taking small steps to walk uphill, towards the top of a local mountain. The higher up the mountain, the better adapted they are to the environment. But sometimes, there turns out to be an even higher summit further on. Those wishing to reach that other summit will first have to go through a valley. Normally, this is not possible, as the evolutionary race compels every being to go higher. Those who go lower will lose and die out.”

Organisms with a full genome (blue) can only reach the fitness summit of the mountain they are already climbing, even if there are higher summits further ahead. A genetic defect can put an organism into a fitness valley (red), which means the organism may yet reach higher peaks in the long term.

“In principle, evolution might sometimes get stuck on a local hill, like the Baraque de Fraiture, without much prospect of becoming even stronger and reaching the summit of Mont Blanc or Mount Everest. And yet, we see that evolution does not come to standstill, with dramatic improvements occurring every so often whereby organisms are climbing a new, higher peak,” adds professor Rob Jelier. “Our research now demonstrates that genetic defects may offer a potential explanation. Such defects occur spontaneously and they can send an organism tumbling back down a mountain at a stroke. At first glance, the organism is weaker, but with a bit of luck, that valley will be just what grants them access to a higher peak that the healthy organisms cannot reach, being as it were entrapped on the local Baraque de Fraiture.”

“Naturally, this does not occur with all genetic defects – sometimes, the organism is weakened to such an extent that it can no longer evolve. It comes down to getting back onto a peak quickly, as otherwise, evolution is merciless. We also see that a defect in various genes with a similar function often leads to the same route to the same new mountain top, or instead to a deep valley from which there can be no escape. This is teaching us a great deal more about the map of the evolutionary landscape.”

Our results show that genetic defects do not have to be detrimental. They are a necessary component of the evolutionary process, because they can provide a longer-term advantage.

Leap forward

“Our results show that genetic defects do not have to be detrimental,” concludes Jana Helsen. “They are a necessary component of the evolutionary process, because they can provide a longer-term advantage. Evolution is not aimed at the individual, but rather at the future and their descendants’ chances of survival. This is why a step backward can sometimes be needed in order to leap forward again later. Human beings also have some 100 defective genes on average. This might weaken the individual to an extent, but that might mean their descendants will become better mountaineers.”

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