Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
Jingchuan Luo, Luís A. Vale-Silva, Adhithi R. Raghavan, Guillaume Mercy, Jonna Heldrich, Xiaoji Sun, Mingyu Li, Weimin Zhang, Neta Agmon, Kun Yang, Jitong Cai, Giovanni Stracquadanio, Agnès Thierry, Yu Zhao, Camila Coelho, Laura H. McCulloch, Stephanie Lauer, Greg Adoff, Ju Young Ahn, Anvesh Annadanam, Surekha Annadanam, Henri Berger, Yi Chen, Michael Chickering, Andrew D’Avino, Oren Fishman, Jay Im, Sang-Min Kim, Sunghan Kim, Hong Seo Lim, Lauren Meyer, Allison Moyer, Natalie A. Murphy, Peter Natov, Arthur Radley, Lisa Z. Scheifele, Arushi Tripathy, Rebeca Vergara Greeno, Tony T. Wang, Nick Wilkerson, Karen Zeller, Tony Zheng, Vivian Zhou, David B. Kaback, Joel S. Bader, Leslie A. Mitchell, Julien Mozziconacci, Romain Koszul, Andreas Hochwagen, Jef D. Boeke
Abstract
We designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems.