Information theory is a powerful tool for understanding the DNA and RNA patterns that define genetic control systems. My theoretical work is divided into several levels. Level 0 is the study of genetic sequences bound by proteins or other macromolecules, briefly described below. The success of this theory suggested that other aspects of information theory should also apply to molecular biology. Level 1 theory introduces the more general concept of the molecular machine, and the concept of a machine capacity equivalent to Shannon's channel capacity. In Level 2, the Second Law of Thermodynamics is connected to the capacity theorem. This defines the limits of Maxwell's Demon and future molecular computers. The project also has three interrelated activities: theory, computer analysis and genetic engineering experiments. In level 0 I showed that binding sites on nucleic acids usually contain just about the amount of information needed for molecules to find the sites in the genome. Apparent exceptions to this """"""""working hypothesis"""""""" have revealed many new phenomena. The first major anomaly was found at bacteriophage T7 promoters, which conserve twice as much information as the polymerase requires to locate them. The most likely explanation is that a second protein binds to the DNA. In another case, we discovered that the F incD region has a three-fold excess conservation, which implies that three proteins bind there. We are investigating both anomalies experimentally. Two graphical methods have been invented to display the structure of binding sites. A sequence logo shows the average patterns in a set of binding sites. The recently invented walker shows individual binding sites. Displaying many walkers simultaneously has become such a powerful tool for investigating genetic structure that it will undoubtedly replace consensus sequences. Walkers can be used to distinguish mutations from polymorphisms, and this has clinical applications. See www.lecb.ncifcrf.gov/~toms/schneider.html for further information.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC008396-14
Application #
6762011
Study Section
(LECB)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Jeong, Jae-Ho; Kim, Hyun-Ju; Kim, Kun-Hee et al. (2012) An unusual feature associated with LEE1 P1 promoters in enteropathogenic Escherichia coli (EPEC). Mol Microbiol 83:612-22
Shultzaberger, Ryan K; Chen, Zehua; Lewis, Karen A et al. (2007) Anatomy of Escherichia coli sigma70 promoters. Nucleic Acids Res 35:771-88
Bindewald, Eckart; Schneider, Thomas D; Shapiro, Bruce A (2006) CorreLogo: an online server for 3D sequence logos of RNA and DNA alignments. Nucleic Acids Res 34:W405-11
Schneider, Thomas D (2006) Claude Shannon: biologist. The founder of information theory used biology to formulate the channel capacity. IEEE Eng Med Biol Mag 25:30-3
Schneider, Thomas D (2006) Twenty Years of Delila and Molecular Information Theory: The Altenberg-Austin Workshop in Theoretical Biology Biological Information, Beyond Metaphor: Causality, Explanation, and Unification Altenberg, Austria, 11-14 July 2002. Biol Theory 1:250-260
Chen, Zehua; Schneider, Thomas D (2006) Comparative analysis of tandem T7-like promoter containing regions in enterobacterial genomes reveals a novel group of genetic islands. Nucleic Acids Res 34:1133-47
Khan, Sikandar G; Metin, Ahmet; Gozukara, Engin et al. (2004) Two essential splice lariat branchpoint sequences in one intron in a xeroderma pigmentosum DNA repair gene: mutations result in reduced XPC mRNA levels that correlate with cancer risk. Hum Mol Genet 13:343-52
Hengen, Paul N; Lyakhov, Ilya G; Stewart, Lisa E et al. (2003) Molecular flip-flops formed by overlapping Fis sites. Nucleic Acids Res 31:6663-73
Schneider, Thomas D (2002) Consensus sequence Zen. Appl Bioinformatics 1:111-9
Emmert, S; Schneider, T D; Khan, S G et al. (2001) The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms. Nucleic Acids Res 29:1443-52

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