Universal Molecular Computation in Ciliates

How do cells and nature “compute”? They read and “rewrite” DNA all the time, by processes that modify sequences at the DNA or RNA level. In 1994, Adleman’s elegant solution to a seven-city Directed Hamiltonian Path problem using DNA [1] launched the new field of DNA computing, which in a few years has grown to international scope. However, unknown to this field, ciliated protozoans of genus Oxytricha and Stylonychia had solved a potentially harder problem using DNA several million years earlier. The solution to this “problem”, which occurs during the process of gene unscrambling, represents one of nature’s ingenious solutions to the problem of the creation of genes. Here we develop a model for the guided homologous recombinations that take place during gene rearrangement and prove that such a model has the computational power of a Turing machine, the accepted formal model of computation. This indicates that, in principle, these unicellular organisms may have the capacity to perform at least any computation carried out by an electronic computer.

[1]  D M Prescott,et al.  Evolution of internal eliminated segments and scrambling in the micronuclear gene encoding DNA polymerase alpha in two Oxytricha species. , 1997, Nucleic acids research.

[2]  Rani Siromoney,et al.  Circular DNA and Splicing Systems , 1992, ICPIA.

[3]  L F Landweber,et al.  The boundaries of partially edited transcripts are not conserved in kinetoplastids: implications for the guide RNA model of editing. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Arto Salomaa,et al.  Formal languages , 1973, Computer science classics.

[5]  D. Pixton Linear and circular splicing systems , 1995, Proceedings First International Symposium on Intelligence in Neural and Biological Systems. INBS'95.

[6]  D M Prescott,et al.  Analysis of a scrambled gene: the gene encoding alpha-telomere-binding protein in Oxytricha nova. , 1992, Genes & development.

[7]  Gheorghe Paun,et al.  On the power of the splicing operation , 1995, Int. J. Comput. Math..

[8]  Satoshi Kobayashi,et al.  On the power of circular splicing systems and DNA computability , 1997, Proceedings of 1997 IEEE International Conference on Evolutionary Computation (ICEC '97).

[9]  L. Klobutcher,et al.  Circular forms of developmentally excised DNA in Euplotes crassus have a heteroduplex junction. , 1993, Genes & development.

[10]  L F Landweber,et al.  The evolution of cellular computing: nature's solution to a computational problem. , 1999, Bio Systems.

[11]  D M Prescott,et al.  Scrambling of the actin I gene in two Oxytricha species. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[12]  L M Adleman,et al.  Molecular computation of solutions to combinatorial problems. , 1994, Science.

[13]  R. W. Gatterdam,et al.  On the undecidability of splicing systems , 1989 .

[14]  Samuel Eilenberg,et al.  Automata, languages, and machines. A , 1974, Pure and applied mathematics.

[15]  Lawrence A. Klobutcher,et al.  Detection of circular forms of eliminated DNA during macronuclear development in E. crassus , 1989, Cell.

[16]  Grzegorz Rozenberg,et al.  Handbook of Formal Languages , 1997, Springer Berlin Heidelberg.

[17]  Katsushi Inoue,et al.  Parallel Image Analysis , 1992, Lecture Notes in Computer Science.

[18]  Gheorghe Paun,et al.  Language Theory and Molecular Genetics: Generative Mechanisms Suggested by DNA Recombination , 1997, Handbook of Formal Languages.

[19]  D M Prescott,et al.  Internal Eliminated Segments (IESs) of Oxytrichidae 1 , 1996, Journal of Eukaryotic Microbiology.

[20]  T. Head Formal language theory and DNA: an analysis of the generative capacity of specific recombinant behaviors. , 1987, Bulletin of mathematical biology.

[21]  H. Lipps,et al.  Sequential excision of internal eliminated DNA sequences in the differentiating macronucleus of the hypotrichous ciliate Stylonychia lemnae. , 1996, Nucleic acids research.

[22]  Eric Meyer,et al.  Epigenetic Programming of Developmental Genome Rearrangements in Ciliates , 1996, Cell.

[23]  D. Bartel,et al.  Isolation of new ribozymes from a large pool of random sequences [see comment]. , 1993, Science.

[24]  Gheorghe Paun,et al.  DNA computing based on splicing: universality results. , 1996, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[25]  Tom Head,et al.  Splicing Schemes and DNA , 1992 .