Skip to main content
SpringerLink
Log in

Genome Informatics: The Role of DNA in Cellular Computations

  • Published:
Biological Theory Aims and scope Submit manuscript

Abstract

Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences (data files) and repetitive sequences (generic formatting signals) contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein complexes, epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular Biology of the Cell. 4th ed. New York: Garland.

    Google Scholar 

  • Almeida R, Allshire RC (2005) RNA silencing and genome regulation. Trends in Cell Biology 15: 251–258.

    Google Scholar 

  • Arabidopsis Genome Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408: 796–815.

    Google Scholar 

  • Armitage JP, Holland IB, Jenal U, Kenny B (2005) “Neural networks” in bacteria: Making connections. Journal of Bacteriology 187: 26–36.

    Google Scholar 

  • Arnone MI, Davidson EH (1997) The hardwiring of development: Organization and function of genomic regulatory systems. Development 124: 1851–1864.

    Google Scholar 

  • Atlan H, Koppel M (1990) The cellular computer DNA: Program or data. Bulletin of Mathematical Biology 52: 335–348.

    Google Scholar 

  • Avery OT, MacLeod CM, McCarty M (1944) Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Induction of transformation by a deoxyribonucleic acid fraction isolated from Pneumococcus Type III. Journal of Experimental Medicine 79: 137–158.

    Google Scholar 

  • Bailey JA, Liu G, Eichler EE (2003) An Alu transposition model for the origin and expansion of human segmental duplications. American Journal of Human Genetics 73: 823–834.

    Google Scholar 

  • Bapteste E, Boucher Y, Leigh J, Doolittle WF (2004) Phylogenetic reconstruction and lateral gene transfer. Trends in Microbiology 12: 406–411.

    Google Scholar 

  • Benzer S (1962) The fine structure of the gene. Scientific American 206: 70–84.

    Google Scholar 

  • Bernstein E, Allis CD (2005) RNA meets chromatin. Genes and Development 19: 1635–1655.

    Google Scholar 

  • Bibikova M, et al. (2006) Human embryonic stem cells have a unique epigenetic signature. Genome Research 16: 1075–83.

    Google Scholar 

  • Bird A (2002) DNA methylation patterns and epigenetic memory. Genes and Development 16: 6–21.

    Google Scholar 

  • Bonifacino JS, Glick BS (2004) The mechanisms of vesicle budding and fusion. Cell 116: 153–166.

    Google Scholar 

  • Bray D (1990) Intracellular signalling as a parallel distributed process. Journal of Theoretical Biology 143: 215–231.

    Google Scholar 

  • Bray D (1995) Protein molecules as computational elements in living cells. Nature 376: 307–312.

    Google Scholar 

  • Bray D, Duke T (2004) Conformational spread: The propagation of allosteric states in large multiprotein complexes. Annual Review of Biophysics and Biomolecular Structure 33: 53–73.

    Google Scholar 

  • Bregliano, JC, Kidwell MG (1983) Hybrid dysgenesis determinants: In: Mobile Genetic Elements (Shapiro JA, ed), 363–410. New York: Academic Press.

    Google Scholar 

  • Britten RJ (1996) DNA sequence insertion and evolutionary variation in gene regulation. Proceedings of the National Academy of Sciences USA 93: 9374–9377.

    Google Scholar 

  • Brosius J (1999) RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements. Gene 238: 115–134.

    Google Scholar 

  • Brosius J (2003) The contribution of RNAs and retroposition to evolutionary novelties. Genetica 118: 99–116.

    Google Scholar 

  • Butturini A, Sthivelman E, Canaani E, Gale RP (1988) Oncogenes in human leukemias. Cancer Investigation 6: 305–316.

    Google Scholar 

  • Carroll SB (1995) Homeotic genes and the evolution of arthropods and chordates. Nature 376: 479–485.

    Google Scholar 

  • Cases I, de Lorenzo V (1998) Expression systems and physiological control of promoter activity in bacteria. Current Opinion in Microbiology 1: 303–310.

    Google Scholar 

  • Craig NL, Craigie R, Gellert M, Lambowitz AM (2002) Mobile DNA II. Washington DC: ASM Press.

    Google Scholar 

  • Crick F (1970) Central dogma of molecular biology. Nature 227: 561–563.

    Google Scholar 

  • Davidson EH (2001) Genomic Regulatory Systems: Development and Evolution. San Diego: Academic Press.

    Google Scholar 

  • Davidson EH, Britten RJ (1979) Regulation of gene expression: Possible role of repetitive sequences. Science 204: 1052–1059.

    Google Scholar 

  • Driesch H (1908) The Science and Philosophy of the Organism. London: A&C Black.

    Google Scholar 

  • Duboule D, Wilkins AS (1998) The evolution of “bricolage.” Trends in Genetics 14: 54–59.

    Google Scholar 

  • Eichler EE (2001) Recent duplication, domain accretion and the dynamic mutation of the human genome. Trends in Genetics 17: 661–669.

    Google Scholar 

  • Eichler EE, Sankoff D (2003) Structural dynamics of eukaryotic chromosome evolution. Science 301: 793–797.

    Google Scholar 

  • Errede B, Cardillo TS, Wever G, Sherman F, Stiles JI, Friedman LR, Sherman F (1981) Studies on transposable elements in yeast. I. ROAM mutations causing increased expression of yeast genes: Their activation by signals directed toward conjugation functions and their formation by insertion of Ty1 repetitive elements. II. deletions, duplications, and transpositions of the COR segment that encompasses the structural gene of yeast iso-1-cytochrome c. Cold Spring Harbor Symposium Quantitative Biology 45 (Pt 2): 593–607.

    Google Scholar 

  • Galli C, Lagutina I, Lazzari G (2003) Introduction to cloning by nuclear transplantation. Cloning Stem Cells 5: 223–232.

    Google Scholar 

  • Gao S, Latham KE (2004) Maternal and environmental factors in early cloned embryo development. Cytogenetic and Genome Research 105: 279–284.

    Google Scholar 

  • Gellert M (2002) V(D)J recombination: RAG proteins, repair factors, and regulation. Annual Review of Biochemistry 71: 101–132.

    Google Scholar 

  • Gerhart J, Kirschner M (1997) Cells, Embryos, and Evolution. Malden, MA: Blackwell Science.

    Google Scholar 

  • Goday C, Esteban MR (2001) Chromosome elimination in sciarid flies. Bioessays 23: 242–250.

    Google Scholar 

  • Goff SA, Ricke D, Lan TH, Presting G, Wang R, Dunn M, Glazebrook J, Sessions A, Oeller P, Varma H, and 45 others (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. japonica). Science 296: 92–100.

    Google Scholar 

  • Gurdon JB, Byrne JA, Simonsson S (2003) Nuclear reprogramming and stem cell creation. Proceedings of the National Academy of Sciences USA 100 (Suppl 1): 11819–11822.

    Google Scholar 

  • Haber JE (1998) Mating-type gene switching in Saccharomyces cerevisiae. Annual Review of Genetics 32: 561–599.

    Google Scholar 

  • Hall IM, Noma K, Grewal SI (2003) RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast. Proceedings of the National Academy of Sciences USA 100: 193–198.

    Google Scholar 

  • Harden N, Ashburner M (1990) Characterization of the FB-NOF transposable element of Drosophila melanogaster. Genetics 126: 387–400.

    Google Scholar 

  • Hartmann N, Scherthan H (2004) Characterization of ancestral chromosome fusion points in the Indian muntjac deer. Chromosoma 112: 213–220.

    Google Scholar 

  • Hartwell L (1992) Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. Cell 71: 543–546.

    Google Scholar 

  • Hartwell LH, Hopfield JJ, Leibler S, Murray AW (1999) From molecular to modular cell biology. Nature 402 (Suppl 6761): C47–C52.

    Google Scholar 

  • Hazelrigg T, Levis R, Rubin GM (1984) Transformation of white locus DNA in drosophila: Dosage compensation, zeste interaction, and position effects. Cell 36: 469–481.

    Google Scholar 

  • Henikoff S, Ahmad K (2005) Assembly of variant histones into chromatin. Annual Review of Cell and Developmental Biology 21: 133–153.

    Google Scholar 

  • Hey J (2003) Speciation and inversions: Chimps and humans. Bioessays 25: 825–828.

    Google Scholar 

  • International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.

    Google Scholar 

  • Jacob F, Monod J (1961) Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology 3: 318–356.

    Google Scholar 

  • Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nature Genetics 33 (Suppl): 245–254.

    Google Scholar 

  • Jenuwein T (2002) An RNA-guided pathway for the epigenome. Science 297: 2215–2218.

    Google Scholar 

  • Jiang N, Bao Z, Zhang X, Eddy SR, Wessler SR (2004) Pack-MULE transposable elements mediate gene evolution in plants. Nature 431: 569–573.

    Google Scholar 

  • Jordan IK, Makarova KS, Spouge JL, Wolf YI, Koonin EV (2001) Lineage-specific gene expansions in bacterial and archaeal genomes. Genome Research 11: 55–65.

    Google Scholar 

  • Jordan IK, Rogozin IB, Glazko GV, Koonin EV (2003) Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends in Genetics 19: 68–72.

    Google Scholar 

  • Judson HF (1979) The Eighth Day of Creation: Makers of the Revolution in Biology. New York: Simon and Schuster.

    Google Scholar 

  • Kinoshita K, Honjo T (2001) Linking class-switch recombination with somatic hypermutation. Nature Reviews Molecular Cell Biology 2: 493–503.

    Google Scholar 

  • Kosak ST, Groudine M (2004) Gene order and dynamic domains. Science 306: 644–647.

    Google Scholar 

  • Kuhn TS (1962) The Structure of Scientific Revolutions. Chicago: University of Chicago Press.

    Google Scholar 

  • Kunkel TA, Erie DA (2005) DNA mismatch repair. Annual Review of Biochemistry 74: 681–710.

    Google Scholar 

  • Landy A (1989) Dynamic, structural, and regulatory aspects of lambda site-specific recombination. Annual Review of Biochemistry 58: 913–949.

    Google Scholar 

  • Levis R, Hazelrigg T, Rubin GM (1985) Effects of genomic position on the expression of transduced copies of the white gene of Drosophila. Science 229: 558–561.

    Google Scholar 

  • Li E (2002) Chromatin modification and epigenetic reprogramming in mammalian development. Nature Reviews Genetics 3: 662–673.

    Google Scholar 

  • Lippman Z, Gendrel AV, Black M, Vaughn MW, Dedhia N, McCombie WR, Lavine K, Mittal V, May B, Kasschau KD, Carrington JC, Doerge RW, Colot V, Martienssen R (2004) Role of transposable elements in heterochromatin and epigenetic control. Nature 430: 471–476.

    Google Scholar 

  • London M, Hausser M (2005) Dendritic computation. Annual Review of Neuroscience 28: 503–532.

    Google Scholar 

  • Lucas I, Hyrien O (2000) Hemicatenanes form upon inhibition of DNA replication. Nucleic Acids Research 28: 2187–2193.

    Google Scholar 

  • Mann JR (2001) Imprinting in the germ line. Stem Cells 19: 287–294.

    Google Scholar 

  • Marino-Ramirez L, Lewis KC, Landsman D, Jordan IK (2005) Transposable elements donate lineage-specific regulatory sequences to host genomes. Cytogenetic and Genome Research 110: 333–341.

    Google Scholar 

  • McClintock B (1984) Significance of responses of the genome to challenge. Science 226: 792–801.

    Google Scholar 

  • Moran JV, DeBerardinis RJ, Kazazian HH Jr (1999) Exon shuffling by L1 retrotransposition. Science 283: 1530–1534.

    Google Scholar 

  • Mouse Genome Sequencing Consortium (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.

    Google Scholar 

  • Murai KK, Pasquale EB (2004) Eph receptors, ephrins, and synaptic function. Neuroscientist 10: 304–314.

    Google Scholar 

  • Muller C, Leutz A (2001) Chromatin remodeling in development and differentiation. Current Opinion in Genetics and Development 11: 167–174.

    Google Scholar 

  • Muller F, Bernard V, Tobler H (1996) Chromatin diminution in nematodes. Bioessays 18: 133–138.

    Google Scholar 

  • Muotri AR, Chu VT, Marchetto MCN, Deng W, Moran JV, Gage FH (2005) Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition. Nature 435: 903–910.

    Google Scholar 

  • Murray AW (2004) Recycling the cell cycle: Cyclins revisited. Cell 116: 221–234.

    Google Scholar 

  • Navarro A, Barton NH (2003) Chromosomal speciation and molecular divergence: accelerated evolution in rearranged chromosomes. Science 300: 321–324.

    Google Scholar 

  • Neel NF, Schutyser E, Sai J, Fan GH, Richmond A (2005) Chemokine receptor internalization and intracellular trafficking. Cytokine and Growth Factor Reviews 16: 637–658.

    Google Scholar 

  • Nei M, Rooney AP (2005) Concerted and birth-and-death evolution of multigene families. Annual Review of Genetics 22: 121–152.

    Google Scholar 

  • Nusslein-Volhard C (1991) Determination of the embryonic axes of Drosophila. Development, (Suppl 1): 1–10.

  • Patel NH, Prince VE (2000) Beyond the Hox complex. Genome Biology 1: reviews 1027.1–1027.4.

    Google Scholar 

  • Peaston AE, et al. (2004) Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Developmental Cell 7: 597–606.

    Google Scholar 

  • Pelkmans L (2005) Viruses as probes for systems analysis of cellular signalling, cytoskeleton reorganization and endocytosis. Current Opinion in Microbiology 8: 331–337.

    Google Scholar 

  • Pollard TD, Borisy GG (2003) Cellular motility driven by assembly and disassembly of actin filaments. Cell 112: 453–465.

    Google Scholar 

  • Pool MR (2005) Signal recognition particles in chloroplasts, bacteria, yeast and mammals (review). Molecular Membrane Biology 22: 3–15.

    Google Scholar 

  • Prescott DM (2000) Genome gymnastics: Unique modes of DNA evolution and processing in ciliates. Nature Reviews Genetics 1: 191–198.

    Google Scholar 

  • Ptashne M (1986) A Genetic Switch: Phage lambda and Higher Organisms. 2nd ed. Cambridge, MA: Cell Press and Blackwell Scientific.

    Google Scholar 

  • Razin SV, Petrov A, Hair A, Vassetzky YS (2004) Chromatin domains and territories: Flexibly rigid. Critical Reviews in Eukaryotic Gene Expression 214: 79–88.

    Google Scholar 

  • Rothenburg S, Koch-Nolte F, Haag F (2001) DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles. Immunological Reviews 184: 286–298.

    Google Scholar 

  • Schotta G, Ebert A, Dorn R, Reuter G (2003) Position effect variegation and the genetic dissection of chromatin regulation in Drosophila. Seminars in Cell and Developmental Biology 14: 67–75.

    Google Scholar 

  • Shapiro JA (1997) Genome organization, natural genetic engineering, and adaptive mutation. Trends in Genetics 13: 98–104.

    Google Scholar 

  • Shapiro JA (1999) Genome system architecture and natural genetic engineering in evolution. In: Molecular Strategies for Biological Evolution (Caporale L, ed), Annals of the New York Academy of Sciences 870: 23–35.

  • Shapiro JA (2002a) Genome organization and reorganization in evolution: Formatting for computation and function. In: From Epigenesis to Epigenetics: The Genome in Context (Van Speybroeck L, Van de Vijver G, De Waele D, eds), Annals of the New York Academy of Sciences 981: 111–134.

  • Shapiro JA (2002b) A 21st century view of evolution. Journal of Biological Physics 28: 745–764.

    Google Scholar 

  • Shapiro JA (2002c) Repetitive DNA, genome system architecture and genome reorganization. Research in Microbiology 153: 447–453.

    Google Scholar 

  • Shapiro JA (2005) A 21st century view of evolution: Genome system architecture, repetitive DNA, and natural genetic engineering. Gene 345: 91–100.

    Google Scholar 

  • Shapiro JA, Dworkin M, eds (1997) Bacteria as Multicellular Organisms. New York: Oxford University Press.

    Google Scholar 

  • Shapiro JA, von Sternberg R (2005) Why repetitive DNA is essential for genome function. Biological Review 80: 227–250.

    Google Scholar 

  • Sidiropoulou K, Pissadaki EK, Poirazi P (2006) Inside the brain of a neuron. EMBO Reports 7(9): 886–892.

    Google Scholar 

  • Smith GR (1994) Hotspots of homologous recombination. Experientia 50: 234–241.

    Google Scholar 

  • Spemann H (1938) Embryonic Development and Induction. New Haven, CT: Yale University Press.

    Google Scholar 

  • Spemann H, Mangold H (1924) Über Induktion von Embryonanlagen durch Implantation artfremder Organisatoren. Roux’ Archiv für Entwicklungsmechanik 100: 599–638.

    Google Scholar 

  • Spofford JB (1976) Position-effect variegation in Drosophila. In: The Genetics and Biology of Drosophila (Ashburner M, Novitski E, eds), 955–1018. New York: Academic Press.

    Google Scholar 

  • Stros M, Muselikova-Polanska E, Pospisilova S, Strauss F (2004) High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops. Biochemistry 43: 7215–7225.

    Google Scholar 

  • Stuart LM, Ezekowitz RA (2005) Phagocytosis: Elegant complexity. Immunity 22: 539–550.

    Google Scholar 

  • Szurmant H, Ordal GW (2004) Diversity in chemotaxis mechanisms among the bacteria and archaea. Microbiology and Molecular Biology Reviews 68: 301–319.

    Google Scholar 

  • Tonzetich J, Lyttle TW, Carson HL (1988) Induced and natural break sites in the chromosomes of Hawaiian Drosophila. Proceedings of the National Academy of Sciences USA 85: 1717–1721.

    Google Scholar 

  • Turing AM (1950) Computing machineryand intelligence. Mind 59: 433–460.

    Google Scholar 

  • van der Woude MW, Baumler AJ. Phase and antigenic variation in bacteria. Clinical Microbiology Reviews 17: 581–611.

  • Van Driel R, Fransz PF, Verschure PJ (2003) The eukaryotic genome: A system regulated at different hierarchical levels. Journal of Cell Science 116: 4067–4075.

    Google Scholar 

  • von Neumann J, Burks AW (1966) Theory of Self-Reproducing Automata. Urbana: University of Illinois Press.

    Google Scholar 

  • von Sternberg R, Shapiro JA (2005) How repeated retroelements format genome function. Cytogenetic and Genome Research 110: 108–116.

    Google Scholar 

  • Wang JY, Syvanen M (1992) DNA twist as a transcriptional sensor for environmental changes. Molecular Microbiology 6: 1861–1866.

    Google Scholar 

  • Watson JD, Crick FHC (1953) Molecular structure of nucleic acids. Nature 171: 737–738.

    Google Scholar 

  • Wessler SR (1996) Plant retrotransposons: Turned on by stress. Current Biology 6: 959–961.

    Google Scholar 

  • Williamson JR (1994) G-quartet structures in telomeric DNA. Annual Review of Biophysics and Biomolecular Structure 23: 703–730.

    Google Scholar 

  • Wilmut I, Paterson L (2003) Somatic cell nuclear transfer. Oncology Research 13: 303–307.

    Google Scholar 

  • Woese CR (2004) A new biology for a new century. Microbiology and Molecular Biology Reviews 68: 173–186.

    Google Scholar 

  • Wulfing C, Tskvitaria-Fuller I, Burroughs N, Sjaastad MD, Klem J, Schatzle JD (2002) Interface accumulation of receptor/ligand couples in lymphocyte activation: Methods, mechanisms, and significance. Immunological Reviews 189: 64–83.

    Google Scholar 

  • Yuh CH, Bolouri H, Davidson EH (1998) Genomic cis-regulatory logic: Experimental and computational analysis of a sea urchin gene. Science 279: 1896–1902.

    Google Scholar 

  • Zaidi SK, Young DW, Choi JY, Pratap J, Javed A, Montecino M, Stein JL, van Wijnen AJ, Lian JB, Stein GS (2005) The dynamic organization of gene-regulatory machinery in nuclear microenvironments. EMBO Reports 6: 128–133.

    Google Scholar 

  • Zhi D, Raphael B, Price A, Tang H, Pevzner P (2006) Identifying repeat domains in large genomes. Genome Biology 7: R7.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Chicago, IL, USA

    James A. Shapiro

Authors
  1. James A. Shapiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James A. Shapiro.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shapiro, J.A. Genome Informatics: The Role of DNA in Cellular Computations. Biol Theory 1, 288–301 (2006). https://doi.org/10.1162/biot.2006.1.3.288

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1162/biot.2006.1.3.288

Keywords

Search

Navigation