Laboratory populations of bacteria that accumulate hidden genetic variants are capable of surprising evolutionary leaps. As researchers at the University of Zurich have shown, this "cryptic" genetic variation gives bacteria many more opportunities to adapt to rapid environmental changes. This process could also be used to develop new biomolecules for use in medicine.
"Cryptic variation is an underrated process," says Andreas Wagner, an evolutionary biologist at the University of Zurich (UZH) and external professor at the Santa Fe Institute, USA, "and it plays an important role in evolution. Previous work has shown that cryptic variation in natural populations promotes rapid evolutionary adaptation. However, the underlying molecular mechanisms are unclear.
To investigate these mechanisms, Wagner's team worked with populations of the human intestinal bacterium Escherichia coli, which carried a plasmid (a small DNA molecule) with a gene for a yellow fluorescent protein (YFP). The researchers designed a two-stage experiment. In the first step, they used a method that induces mutations to increase the genetic variation in the YFP gene. For the subsequent selection, they chose a narrow range of yellow fluorescence. All bacteria that were not sufficiently yellow were excluded. In this way, they built up accumulations of cryptic genetic variations in the bacterial genetic material without changing the yellow color of the YFP protein.
In the second phase, the team changed the selection rules. Now they selected the E. coli whose YFP protein fluoresces in the green part of the spectrum. As a control, they used bacterial populations without increased cryptic variation in the YFP gene. Those cell lines with a reservoir of cryptic variation developed a green fluorescent protein that was both greener and genetically more diverse than any other protein produced by the control populations.
"In our experiment, cryptic variation has done more than speed up evolutionary adaptation," says co-author Joshua Payne of ETH Zurich. Cell lines with large reserves of cryptic variations developed greener YFP proteins - including forms of the protein that were inaccessible to normal bacteria. And these developed in several unique ways that are not available to normal E. coli.
Today's methods for controlling evolutionary processes in the laboratory often lead to the same evolutionary results. The new work shows that cryptic variation contains mutations that are harmful in themselves in new environmental conditions, but offer advantages in combination with new mutations. "This removes the restrictions that normally occur during genetic adaptations," says first author and UZH researcher Jia Zheng. "It opens doors for the selection of variants of a protein that would otherwise only occur infrequently.
In the laboratory, the cryptic variation could be used to modify a biomolecule in such a way that it binds to a new receptor. "Our work can help to develop targeted evolutionary strategies to find biomolecules for biotechnological and medical applications," adds Zheng. In nature it is crucial for the survival of a population, in the laboratory it becomes a useful tool for molecular biologists.
Jia Zheng, Joshua L. Payne, Andreas Wagner. Cryptic genetic variation accelerates evolution by opening access to various adaptive peaks. Science. July 26, 2019. DOI: 10,1038/s41559-019-0939-6