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Cryptic Genetic Variation might Explain Hitherto Obscure Leaps in Biological Evolution

Posted July 26, 2019

As is well known today, biological evolution proceeds via the accumulation of genetic variants – the more variation there is, the more chances natural selection has to drive novel adaptive solutions in the host individuals and species.

Sometimes, however, evolution seems to take place at a rate that’s much faster than usual, and cryptic genetic variation (CGV) – unexpressed, bottled-up genetic potential – might be one of the reasons why.

“It’s an underappreciated kind of genetic variation,” said Andreas Wagner from the University of Zurich, who’s a co-author on a new study published in the 26 July issue of the journal Science, “and it plays an important role in evolution.”

In the study, Wagner and his colleagues worked with populations of the widely known bacterium E. coli which carried a plasmid with a gene for a yellow fluorescent protein (YFP) for the purposes of accumulating cryptic variation and examining its effects.

Stage 1 of the study consisted of deploying a mutagenic PCR to increase variation in the YFP gene and selecting for a narrow range of yellow fluorescence, which means that bacteria with insufficient levels of fluorescence were excluded from the pool. This allowed the researchers to build up the stores of CGV without altering the colour of the YFP protein.

Stores of typically unexpressed genetic variation may help scientists achieve superior results in artificially driven evolution. Image: Виталий Смолыгин via, CC0 Public Domain

During stage 2 – this time with a control population of E. coli without enhanced cryptic variation in the YFP – the rules of selection changed, with researchers now favouring bacteria exhibiting fluorescence in the green part of the spectrum.

According to co-author Joshua Payne from ETH Zurich, CGV not only provided the conditions necessary for faster-than-usual evolutionary adaptation, but also allowed cell lines with more accumulated cryptic variation to evolve greener YFP proteins, doing so by a variety of different routes not available to their run-of-the-mill counterparts.

This means that, unlike in the case of guided (or lab-driven) evolution, which often results in nearly identical outcomes, techniques involving a ‘piggy bank’ of accrued cryptic variation could lead to otherwise inaccessible regions of the protein sequence space.

“Our work can help develop new directed evolution strategies to find innovative biomolecules for biotechnological and medical applications,” explained co-author on the study Jia Zheng from the University of Zurich.


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