Giovanni Stracquadanio Talk at Quackenbush Lab Meeting – 10/18
Polymer physics of structural evolution in synthetic yeast chromosomesHow to learn something from very small genomic dataTuesday, October 18Lab Meeting: 9:30 -11:00amTalk: 10-11amZoom or In Person (Bldg 2, Rm 426)
Giovanni Stracquadanio, PhD FHEAUKRI EPSRC fellowAssociate Professor in Synthetic BiologyCo-Director of the Edinburgh Genome Foundry School of Biological Sciences, The University of Edinburgh, Edinburgh, UKgithub: github.com/stracquadaniolab
Yeast SCRaMbLE is an experimental method using designed synthetic yeast chromosomes to generate combinatorial diversity through genome rearrangements. These events occur at designed loxPsym recombination sites through the activity of Cre recombinase. While the synthetic SCRaMbLE system was designed to explore minimal genomes and permit rapid genome evolution, the pattern of recombinations also reflects inherent properties of DNA looping required to coalesce pairs of loxPsym sites. Genomes of yeast strains generated by SCRaMbLE are analyzed here using a new statistical mechanics model, called the SCRaMbLE Polymer Interaction (SPI) model. SPI uses polymer physics to model recombinations, and implements efficient rejection sampling and histogram reweighting algorithms to conduct SCRaMbLE experiments in silico. Using SPI, we found that recombination events observed experimentally are consistent with a random walk scaling exponent ranging between 0.45 and 0.6, which spans values of 0.5 for a Gaussian polymer and 0.588 for a self-avoiding walk. SPI provides a highly accurate tool to study SCRaMbLE recombinations and massively parallel genome recombination experiments.
ReferencesPolymer physics of structural evolution in synthetic yeast chromosomes. Giovanni Stracquadanio*, Kun Yang, Jef D. Boeke, Romain Koszul, Joel S. Bader*. bioRxiv, 2022.
