In vivo generation of DNA sequence diversity for cellular barcoding

Nucleic Acids Research
Ian D PeikonAnthony M Zador


Heterogeneity is a ubiquitous feature of biological systems. A complete understanding of such systems requires a method for uniquely identifying and tracking individual components and their interactions with each other. We have developed a novel method of uniquely tagging individual cells in vivo with a genetic 'barcode' that can be recovered by DNA sequencing. Our method is a two-component system comprised of a genetic barcode cassette whose fragments are shuffled by Rci, a site-specific DNA invertase. The system is highly scalable, with the potential to generate theoretical diversities in the billions. We demonstrate the feasibility of this technique in Escherichia coli. Currently, this method could be employed to track the dynamics of populations of microbes through various bottlenecks. Advances of this method should prove useful in tracking interactions of cells within a network, and/or heterogeneity within complex biological samples.


May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R C JohnsonM I Simon
Mar 25, 1981·Journal of Molecular Biology·T F Smith, M S Waterman
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·J A GoldenC L Cepko
Apr 1, 1993·Protein Expression and Purification·J T MooreG F Maley
Apr 27, 2000·Journal of Bacteriology·Atsuko Gyohda, Teruya Komano
Jul 24, 2002·Nucleic Acids Research·Stephen J LangerLeslie Leinwand
May 31, 2003·Nature Reviews. Genetics·Santiago F Elena, Richard E Lenski
May 4, 2005·Trends in Cognitive Sciences·Gerhard Roth, Ursula Dicke
Oct 31, 2012·PLoS Biology·Anthony M ZadorIan D Peikon
Nov 16, 2012·Bulletin of Mathematical Biology·Yi Wei, Alexei A Koulakov
Mar 16, 2013·Science·Carmen GerlachTon N Schumacher


May 27, 2015·Scientific Reports·Kosuke FujishimaLynn J Rothschild
Jul 2, 2016·BMC Systems Biology·Tom S WeberKen R Duffy
Dec 6, 2016·Nature Methods·Reza KalhorGeorge M Church
Mar 4, 2017·Scientific Reports·Lars ThieleckeKerstin Cornils
Nov 9, 2017·Frontiers in Computational Neuroscience·Young-Gyu YoonEdward S Boyden
Nov 1, 2018·Nature Methods·Justus M Kebschull, Anthony M Zador
Nov 30, 2019·Bioinformatics·Lars ThieleckeIngmar Glauche
Apr 28, 2017·Nucleic Acids Research·Ian D PeikonAnthony M Zador
May 22, 2019·Nature Protocols·Weike PeiHans-Reimer Rodewald
Aug 12, 2020·Annual Review of Biomedical Data Science· Sagar, Dominic Grün
Aug 11, 2018·Science·Reza KalhorGeorge M Church
Jun 30, 2019·Development·Aaron McKenna, James A Gagnon
Feb 26, 2020·Nature Ecology & Evolution·Weronika JasinskaShimon Bershtein
Oct 20, 2020·Frontiers in Physiology·Irene Garcia-GonzalezRui Benedito

Datasets Mentioned


Methods Mentioned


Related Concepts

Cre recombinase, Enterobacteria phage P1
Alkalescens-Dispar Group
Variation (Genetics)
Sequence Determinations, DNA
Exon Shuffling, In Vitro
High-Throughput Nucleotide Sequencing
Escherichia coli

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