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Hidden genetic variations allow evolutionary jumps

Genetic variation is the driving force behind all evolutionary changes: the greater the genetic variation, the faster the evolution and the greater the potential for innovative adaptive solutions. But a type of genetic variation - hidden or "cryptic" variation - does not change the appearance or behaviour of an organism in its usual environment.

"cryptic" genetic variations
"This is an underestimated type of genetic variation," said corresponding author Andreas Wagner, evolution biologist at the University of Zurich and external professor at the Santa Fe Institute, "and it plays an important role in evolution. »

Previous work has shown that cryptic variation in natural populations promotes rapid evolutionary adaptation. But the underlying molecular mechanisms were not clear.

To explore this mechanism, Wagner's team worked with populations of the bacterium E. coli, an intestinal microbe that carries a plasmid carrying the yellow fluorescent protein (YFP) gene. The team designed a two-step experiment. In stage 1, they used mutagenic PCR to increase the variation of the YFP gene.

Then they selected a narrow range of yellow fluorescence. All bacteria that are not yellow enough have been excluded, a process called "stabilizing selection". They have thus built up reserves of cryptic genetic variations without altering the yellow colour of the YFP protein.

During Phase 2, the team changed the selection rules and began to select E. coli whose fluorescence passed into the green part of the spectrum. They also introduced E. coli control populations without improved cryptic variation of YFP. E. Coli cell lines with reserves of cryptic variation have developed a green fluorescent protein (from YFP genes), which is greener and more genetically diverse than all those produced by E. Coli control lines.

Joshua Payne, co-author of the experiment, believes that cryptic variation has done more than lead to faster evolutionary adaptation. Cell lines with deep reserves of cryptic variation have evolved into greener YFP proteins, forms of the protein that are inaccessible to regular bacteria, and they have evolved through multiple unique pathways not available for ordinary E. coli.

Cryptic variations open doors to inaccessible variations 
The current evolution led by the laboratory often leads to the same evolutionary results. This new work shows how the combination of cryptic variations can open doors to otherwise inaccessible variations in the space of protein sequences, explains first author Jia Zheng, a post-doctoral researcher at the University of Zurich.

In nature, cryptic variations help fish adapt to life in caves. In the laboratory, cryptic variation could help a biomolecule bind to a new receptor. "Our work could help develop new directed evolution strategies to find innovative biomolecules for biotechnological and medical applications," said Zheng.

Like an increasing savings account, cryptic variation is a reserve of variations that becomes available in an emergency to fuel rapid evolutionary change, which is essential to the survival of a lineage and useful for molecular biologists.