Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

Science. 2017 Mar 10;355(6329):eaaf4791. doi: 10.1126/science.aaf4791.

Abstract

Here, we report the successful design, construction, and characterization of a 770-kilobase synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels-including phenomics, transcriptomics, proteomics, chromosome segregation, and replication analysis-to provide a thorough and comprehensive analysis of a synthetic chromosome. Our Trans-Omics analyses reveal a modest but potentially relevant pervasive up-regulation of translational machinery observed in synII, mainly caused by the deletion of 13 transfer RNAs. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the high-osmolarity glycerol response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Segregation
  • Chromosomes, Artificial, Yeast / chemistry
  • Chromosomes, Artificial, Yeast / genetics
  • Chromosomes, Artificial, Yeast / physiology*
  • Culture Media / chemistry
  • DNA Replication
  • Genome, Fungal*
  • Glycerol
  • Proteomics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Sequence Analysis, DNA
  • Synthetic Biology
  • Transcriptome

Substances

  • Culture Media
  • Glycerol