RT Journal Article
SR Electronic
T1 Polymer physics of structural evolution in synthetic yeast chromosomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.14.507906
DO 10.1101/2022.09.14.507906
A1 Giovanni Stracquadanio
A1 Kun Yang
A1 Jef D. Boeke
A1 Romain Koszul
A1 Joel S. Bader
YR 2022
UL http://biorxiv.org/content/early/2022/09/16/2022.09.14.507906.abstract
AB 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.Competing Interest StatementGiovanni Stracquadanio is a consultant to Neochromosome Inc. and ZenithAI. Joel Bader is a Founder of and consultant to Neochromosome Inc. Jef Boeke is a Founder and Director of CDI Labs, Inc., a Founder of and consultant to Neochromosome, Inc, a Founder, SAB member of and consultant to ReOpen Diagnostics, LLC and serves or served on the Scientific Advisory Board of the following: Sangamo, Inc., Modern Meadow, Inc., Rome Therapeutics, Inc., Sample6, Inc., Tessera Therapeutics, Inc. and the Wyss Institute.