Effect of different serologic transformations of T5 universes

Summary A hypothetical immunogenetic system (T₅) with 2 closely linked loci, 4 simple antigens (x, y, z, t) and 4 complex antigens (ax, ay, az, at) is analyzed after simple-complex, complex-simple and binary restricted complex-complex transformation.It is found that a simple-complex transformation makes this imaginary system very similar to the Fisher-Race model for the Rh-system at the 8 haplotype-9 reagent level, which requires 9 symbols and 3 loci, whereas a complex-simple model requires 8 symbols and 1 locus. The specified complex-complex model finally only requires 5 symbols and 2 loci to account for the same data.

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Zusammenfassung Ein hypothetisches immunogenetisches Modell-System (T₅) mit 2 eng gekoppelten Loci, 4 einfachen Antigenen (x, y, z, t) and 4 komplexen Antigenen (ax, ay, az, at) wurde nach einfach-komplexer, komplex-einfacher und binär-restriktiver Komplex-komplex-Transformation analysiert.Es wurde gefunden, daß die einfach-komplexe Transformation dieses, imaginäre System dem von Fisher and Race entwickelten Modell für das Rh-System (8 Haplotypen und 9 Reagentien) mit 9 Symbolen und 3 Loci sehr ähnlich macht. Die komplex-einfache Transformation führt zu einem Modell mit 8 Symbolen und 1 Locus. Die hier angewandte Komplex-komplex-Transformation schließlich erfordert zur Erlangung derselben Daten nur 5 Symbole und 2 Loci.

     

Information theory and limitations in antibody diversity.

Information theory can be used to assess the efficiency with which information about an antigen is transmitted when using different theories of antibody diversity. Cross-reactivity leads to loss in specificity during an immune response and this imposes severe limitations on antibody diversity produced by a random somatic mutation theory.     

A quantum-theoretic approach to genetic problems

A quantum-theoretic picture of the transfer of genetic information is described. The advantage of such an approach is that a number of genetic effects appear to be explicable on the basis of general microphysical laws, independent of any specific model (such as DNA-protein coding) for the transmission of genetic information. It is assumed that the genetic information is carried by a family of numerical observables belonging to a specific microphysical system; it is shown that a single observable is theoretically sufficient to carry this information. The various types of structure that this observable can possess are then described in detail, and the possible genetic effects which can airse from each such structure are discussed. For example, it is shown how the assumption that the genetic observable possesses degenerate eigenvalues may lead to a theory of allelism. To keep the treatment self-contained, the basic quantum-theoretical principles to be used are discussed in some detail. Finally, the relation of the present approach to current biochemical ideas and to earlier quantum-theoretic treatments of genetic systems is discussed.     

Information analysis of Fis binding sites.

Originally discovered in the bacteriophage Mu DNA inversion system gin, Fis (Factor for Inversion Stimulation) regulates many genetic systems. To determine the base frequency conservation required for Fis to locate its binding sites, we collected a set of 60 experimentally defined wild-type Fis DNA binding sequences. The sequence logo for Fis binding sites showed the significance and likely kinds of base contacts, and these are consistent with available experimental data. Scanning with an information theory based weight matrix within fis, nrd, tgt/sec and gin revealed Fis sites not previously identified, but for which there are published footprinting and biochemical data. DNA mobility shift experiments showed that a site predicted to be 11 bases from the proximal Salmonella typhimurium hin site and a site predicted to be 7 bases from the proximal P1 cin site are bound by Fis in vitro. Two predicted sites separated by 11 bp found within the nrd promoter region, and one in the tgt/sec promoter, were also confirmed by gel shift analysis. A sequence in aldB previously reported to be a Fis site, for which information theory predicts no site, did not shift. These results demonstrate that information analysis is useful for predicting Fis DNA binding.     

Information, discrimination and divergence in cytology. I. Theoretical aspects and definitions

The results of medical tests update the probability of diagnosis (diagnosability) of a patient from the population prevalence of a disease. This paper demonstrates a method of combining several mutually dependent tests as the sum of log odds ratios, and of separating the log odd ratios of the test results and those of prevalences. Extending Kullback's discriminant function between two states to m states (m greater than or equal to 2), it is shown that the information of a test can be measured by discrimination and divergence, which are well-defined measures in information theory and test theory. The performance of diagnostic cytology can then be compared to the results of histopathologic diagnoses or to a peer-reviewed consensus without the use of arbitrarily given scores or without unfounded assumptions about underlying continuous variables. They can also provide a way to optimize the categorization (classification) of Papanicolaou smears and a means of quality control for morphologic tests. These methods can be used to evaluate the performances of cytology laboratories that use two classifications consisting of different numbers of categories (classes) and states.     

Information theory provides a comprehensive framework for the evaluation of protein structure predictions

Protein structure prediction has a number of important ad hoc similarity measures for evaluating predictions, but would benefit from a measure that is able to provide a common framework for a broad range of comparisons. Here we show that a mutual information-like measure can provide a comprehensive framework for evaluating protein structure prediction of all types. We discuss the concept of information, its application to secondary structure, and the obstacle to applying it to 3D structure. On the basis of the insights from the secondary structure case, we present an approach to work around the 3D difficulties, and develop a method to measure the mutual information provided by a 3D structure prediction. We integrate the evaluation of all types of protein structure prediction into a single framework, and compare the amount of information provided by various prediction methods, including secondary structure prediction. Within this broadened framework, the idea that structure is better preserved than sequence during evolution is evaluated quantitatively for the globin family. A nearly perfect sequence match in the globin family corresponds to about 300 bits of information, whereas a nearly perfect structural match for the same two proteins corresponds to about 2500 bits of information, where bits of information describes the probability of obtaining a match of similar closeness by chance. Mutual information provides both a theoretical basis for evaluating structure similarity and an explanatory surround for existing similarity measures.     

What determines the normal water content of a living cell?

Most living cells contain a large amount of water. To improve our understanding of this fundamental phenomenon of cell physiology, five theories are critically examined in the light of three sets of relevant experimental findings. These findings are: (1) the diversity and specificity of the percentage water content to tissue type; (2) the limitation imposed by the Law of the Conservation of Energy on postulating membrane pumps and (3) the non-extractability of cell water from the open ends of muscle cells whose membrane covering has been surgically removed. Two of the five theories examined are called respectively the accidental theory (Theory I) and the direct water pump-leak theory (Theory III); both are introduced for the first time here as working hypotheses. Three others theories examined were published; they comprise the Donnan membrane equilibrium theory (Theory II), the indirect pump-leak (Theory IV) and the polarized-oriented multilayer (PM) theory of cell water (Theory V.) The PM (Theory V) alone is in harmony with, and supported by all three sets of the experimental findings. The remaining theories are shown to be non-applicable to cell water by at least two of the findings     

Human pre-mRNA splicing signals.

A sample of 764 pairs of human pre-mRNA exon-intron and intron-exon boundaries, extracted from the European Molecular Biology Laboratory data bank, is analyzed to provide a species-optimized characterization of donor and acceptor sites, evaluate the information content of the two signals (found to be about 8 and 9 bits respectively) and check the independent-base approximation (which holds well) and the "GT-AG" rule (to which, a few well-documented exceptions are found). No correlation is detected between the strength ("discrimination energy") of an actual donor-site signal and that of its corresponding acceptor-site counterpart, nor between that of either signal, or the cumulative strength of both, and the length of the intervening intron. The discrimination-energy distributions of the two signals are determined. Because of the large sample size and its single-species origin, the two distributions can be presumed to be representative of their underlying genomic counterparts. The size distribution of the introns shows a lower cut-off of 70 nucleotides (in essential agreement with published experimental results), and apparently no periodicities. A smaller sample of mammalian branch sites, taken from the literature, is similarly analyzed to attempt a characterization of this rather elusive signal, and provides some indication that at least part of the "long pyrimidine stretch", usually considered an integral constituent of the 3' splice signal, may be just as strongly associated with the branch site, in agreement with recent experimental observations. The usefulness of these characterizations for splice-junction searches is assessed on a test sequence.     

Correlation between binding rate constants and individual information of E. coli Fis binding sites

Individual protein binding sites on DNA can be measured in bits of information. This information is related to the free energy of binding by the second law of thermodynamics, but binding kinetics appear to be inaccessible from sequence information since the relative contributions of the on- and off-rates to the binding constant, and hence the free energy, are unknown. However, the on-rate could be independent of the sequence since a protein is likely to bind once it is near a site. To test this, we used surface plasmon resonance and electromobility shift assays to determine the kinetics for binding of the Fis protein to a range of naturally occurring binding sites. We observed that the logarithm of the off-rate is indeed proportional to the individual information of the binding sites, as predicted. However, the on-rate is also related to the information, but to a lesser degree. We suggest that the on-rate is mostly determined by DNA bending, which in turn is determined by the sequence information. Finally, we observed a break in the binding curve around zero bits of information. The break is expected from information theory because it represents the coding demarcation between specific and nonspecific binding.     

Theory of exciton annihilation in complexes of a finite number of molecular sites

A theory of the kinematics of singlet exciton annihilation in complexes of a finite number of molecular sites is developed. The theory is based on a specific scheme suggested earlier by Gülen, Wittmershaus, and Knox [Biophys J. 49:469-477 (1986)]. It is adequate to address the excitation kinetics and dynamics in such systems, especially under high excitation intensities. A Pauli master equation is formulated and is solved to give explicit expressions for observables such as quantum yield and fluorescence intensity. The excitation intensity dependence of the observables is taken into account by introducing Poisson statistics. Details relevant to its application to the annihilation of excitons in photosynthetic systems and its connection to earlier theories are presented.     

Trichromacy, opponent colours coding and optimum colour information transmission in the retina

This paper presents a systematic analysis of the role of opponent type processing in colour vision and the relation between opponent type colour transformations and the initial three colour mechanisms. It is shown that efficient information transmission is achieved by a transformation of the initial three colour mechanisms into an achromatic and two opponent chromatic channels. The derivation of the transformation is dependent solely on criteria from information theory. Thus it provides a logical rationale reconciling opponent type processing as an optimal necessary step after the initial three colour mechanisms, unifying respectively the Hering and Young-Helmholtz approaches to colour vision. The effects of chromatic adaptation on the spectral response of the achromatic and two chromatic channels are discussed from the point of view of information theory. It is argued that adaptation serves as a dynamic readjustment of these responses, necessary to meet criteria of efficient colour information transmission. The results are confronted with empirical observations to test the principles of the theory and the relation to other theories is discussed. Within the same framework the issue of trichromacy is discussed. It is argued that a broad class of typical colour spectra can effectively be represented by three significant degrees of freedom that make up a trichromatic system.     

The third leg: Molecular dynamics simulations of lipid binding proteins

Molecular dynamics computer simulations can provide a third leg which balances the contributions of both structural biology and binding studies performed on the lipid binding protein family. In this context, these calculations help to establish a dialogue between all three communities, by relating experimental observables with details of structure. Working towards this connection is important, since experience has shown the difficulty of inferring thermodynamic properties from a single static conformation. The challenge is exemplified by ongoing attempts to interpret the impact of mutagenesis on structure and function (i.e. binding). A detailed atomic-level understanding of this system could be achieved with the support of all three legs, paving the way towards rational design of proteins with novel specificities. This paper provides an outline of the connections possible between experiment and theory concerning lipid binding proteins.     

Approach and following behaviour of 24-hr old chicks as a function of stimulus complexity.

In a straight runway, following or approach behaviour of day-old broiler and leghorn chicks was found to be mainly a linearly decreasing function of stimulus complexity. The patterned stimuli used were checkerboard-like matrices containing, on the average, 4, 36, 100, 400, or 900 bits of information. Preference for simpler stimuli was not found to depend upon experience in the test situation nor upon the degree of complexity of the home pen. When stimulus illuminance was varied, there was a tendency for a plain grey square (zero bits) to be preferred over the pattern containing 4 bits of information, suggesting that approach or following behaviour is energized maximally by some optimal combination of stimulus illuminance and complexity.     

Excess information at bacteriophage T7 genomic promoters detected by a random cloning technique.

In our previous analysis of the information at binding sites on nucleic acids, we found that most of the sites examined contain the amount of information expected from their frequency in the genome. The sequences at bacteriophage T7 promoters are an exception, because they are far more conserved (35 bits of information content) than should be necessary to distinguish them from the background of the Escherichia coli genome (17 bits). To determine the information actually used by the T7 RNA polymerase, promoters were chemically synthesized with many variations and those that function well in an in vivo assay were sequenced. Our analysis shows that the polymerase uses 18 bits of information, so the sequences at phage genomic promoters have significantly more information than the polymerase needs. The excess may represent the binding site of another protein.     

Energy transfer in photosynthesis

A theoretical model is presented to account for the physical mechanism of energy transfer from antenna molecules to the reaction centers in photosynthesis. The energy transfer is described by a generalized transport equation or “master equation”. The solution of this equation for the proposed model gives a relationship between the antennae interaction energy and the transfer rate. The results are shown to be in agreement with inter-antenna transfer rates calculated from experimental fluorescence lifetimes. Previous theories were based either on the Förster mechanism, which is valid for very small interaction energies, or an exciton model valid for very large interactions, but experimental results seemed to indicate that the actual situation was intermediate between these two. The Förster theory and the exciton model are limiting cases of the master equation.