An Exactly Solvable Model of Random Site-Specific Recombinations
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Cre-lox and other systems are used as genetic tools to control site-specific recombination (SSR) events in genomic DNA. If multiple recombination sites are organized in a compact cluster within the same genome, a series of random recombination events may generate substantial cell specific genomic diversity. This diversity is used, for example, to distinguish neurons in the brain of the same multicellular mosaic organism, within the brainbow approach to neuronal connectome. In this paper, we study an exactly solvable statistical model for SSR operating on a cluster of recombination sites. We consider two types of recombination events: inversions and excisions. Both of these events are available in the Cre-lox system. We derive three properties of the sequences generated by multiple recombination events. First, we describe the set of sequences that can in principle be generated by multiple inversions operating on the given initial sequence. We call this description the ergodicity theorem. On the basis of this description, we calculate the number of sequences that can be generated from an initial sequence. This number of sequences is experimentally testable. Second, we demonstrate that after a large number of random inversions every sequence that can be generated is generated with equal probability. Lastly, we derive the equations for the probability to find a sequence as a function of time in the limit when excisions are much less frequent than inversions, such as in shufflon sequences.
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- Cao, G., Oyibo, H. H., Zhan, H., Znamenskiy, P., Koulakov, A., Enquist, L., Dubnau, J., & Zador, A. (2011). Neural connectivity as a DNA sequencing problem in vitro. In Society for neuroscience annual meeting (p. 840.11/ZZ63).
- Hampel, S., et al. (2011). Drosophila brainbow: a recombinase-based fluorescence labeling technique to subdivide neural expression patterns. Nat. Methods, 8, 253. CrossRef
- Horn, R. A., & Johnson, C. R. (1994). Topics in matrix analysis. Cambridge: Cambridge University Press. ed. 1st pbk, (pp. viii, 607 p.).
- Komano, T. (1999). Shufflons: multiple inversion systems and integrons. Annu. Rev. Genet., 33, 171. CrossRef
- Lichtman, J. W., Livet, J., & Sanes, J. R. (2008). A technicolour approach to the connectome. Nat. Rev. Neurosci., 9, 417. CrossRef
- Livet, J., et al. (2007). Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature, 450, 56. CrossRef
- Lu, R., Neff, N. F., Quake, S. R., & Weissman, I. L. (2011). Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding. Nat. Biotechnol., 29, 928. CrossRef
- Nagy, A. (2000). Cre recombinase: the universal reagent for genome tailoring. Genesis, 26, 99. CrossRef
- Norris, J. R. (1997). Markov chains. Cambridge series in statistical and probabilistic mathematics (pp. xvi, 237). Cambridge: Cambridge University Press.
- Oyibo, H. H., Cao, G., Zhan, H., Znamenskiy, P. C., Koulakov, A., Enquist, L., Dubnau, J., & Zador, A. (2011). Neural connectivity as a DNA sequencing problem in vivo. In Society for neuroscience annual meeting (pp. 617.25/XX57).
- Sauer, B. (1987). Functional expression of the cre-lox site-specific recombination system in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol., 7, 2087.
- Sauer, B., & Henderson, N. (1988). Site-specific DNA recombination in mammalian cells by the cre recombinase of bacteriophage P1. Proc. Natl. Acad. Sci. USA, 85, 5166. CrossRef
- Van Duyne, G. D. (2001). A structural view of cre-loxp site-specific recombination. Annu. Rev. Biophys. Biomol. Struct., 30, 87. CrossRef
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- An Exactly Solvable Model of Random Site-Specific Recombinations
Bulletin of Mathematical Biology
Volume 74, Issue 12 , pp 2897-2916
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- Site-specific recombination (SSR)
- Markov process