title: Evolutionary design of multiple genes encoding the same protein.
abstract: BACKGROUND
  Enhancing expression levels of a target protein is an important goal in synthetic biology. A widely used strategy is to integrate multiple copies of genes encoding a target protein into a host organism genome. Integrating highly similar sequences, however, can induce homologous recombination between them, resulting in the ultimate reduction of the number of integrated genes.
  
  
  RESULTS
  We propose a method for designing multiple protein-coding sequences (i.e. CDSs) that are unlikely to induce homologous recombination, while encoding the same protein. The method, which is based on multi-objective genetic algorithm, is intended to design a set of CDSs whose nucleotide sequences are as different as possible and whose codon usage frequencies are as highly adapted as possible to the host organism. We show that our method not only successfully designs a set of intended CDSs, but also provides insight into the trade-off between nucleotide differences among gene copies and codon usage frequencies.
  
  
  METHODS
  Our method, named Tandem Designer, is available as a web-based application at http://tandem.trahed.jp/tandem/ .
  
  
  BACKGROUND
  : terai_goro@intec.co.jp or asai@k.u-tokyo.ac.jp.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, Japan.|INTEC Inc, Kanagawa-ku, Yokohama, Kanagawa, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Terai
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, Japan.|INTEC Inc, Kanagawa-ku, Yokohama, Kanagawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kamegai
authors.affiliation: Graduate School of Science and Technology, Hirosaki University, Hirosaki, Aomori, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Taneda
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, Japan.|Graduate School of Frontier Sciences, University of Tokyo, Kashiwa Chiba, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asai
mesh_terms: D000465:Algorithms; D005075:Biological Evolution; D003062:Codon; D059765:Homologous Recombination; D016366:Open Reading Frames; D011506:Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods
chemical_list: D003062:Codon; D011506:Proteins