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Everybody! Our latest work on the evolution of #integron integrases is out! I shout it because it has been an extremely long and tough project! Thanks @amazeld @aleks_nivina and collaborators! Here is what it is about (thread) https://doi.org/10.7554/eLife.58061
Integrases are tyrosine recombinases with a twist: instead of recombining exclusively ds-DNA, integrases can recombine ss-DNA with ss- or ds-DNA to excise or capture cassettes, providing a phenomenal adaptive value to the bacterial host.
To recognise and process ss-DNA they have a domain that is nowhere else to be found in nature: the I2 helix. But it is puzzling whether the acquisition of this domain within the core of the protein could take place without impacting negatively the ancestral activity.
So to understand how this happened what we have done here is to evolve the integrase towards its ancestral function (reactions between ds-DNA substrates)using synonymous recoding to enlarge the evolutionary landscape.
We ended up with proteins showing a 10.000 fold (!) increase in ancestral activity and asymmetrical trade-offs in the modern one.
We have used a combinatorial library to study epistasis among the mutations we found.
We have used a combinatorial library to study epistasis among the mutations we found.
So to make a very long story short... we show that the I2 domain is compatible with high levels of ancestral activity. This solves (a bit at least) the chicken-egg paradox that evolution of integrases raises and leaves the rest of the process to co-evolution.
