On the role of chemical systems in the microphysical aspects of primary genetic mechanisms

It is pointed out that two fundamentally different views of primary genetic processes occur in the literature which are frequently confused. The first is a true communication-theoretic view, which regards the genetic apparatus as containing a real information-source and a transducer which converts that information to useful form. The second view is generally expressed as a template scheme based on the Watson-Crick model; it is shown that in this model there is actually no such thing as genetic information in a communication-theoretic sense. Both views are then discussed on the basis of microphysical principles developed in previous work of the author (Bull. Math. Biophysics,22, 227–255, 1960) in an attempt to find which approach is in closer accord with the biological facts. It is shown that, if the communication-theoretic view is correct, then the information-bearing object must act as a “catalyst,” but it is pointed out that the type of catalysis involved must be of a fundamentally different nature than that occurring in familiar enzyme-catalyzed reactions. On the basis of general considerations of irreversible changes in microphysical measuring systems, it is shown that any type of template must suffer a gradual and irreversible denaturation, which seems to make it unlikely that a template could play a primary role in fundamental genetic processes. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command, under Contract AF 49(638)-917.     

Optimal sampling for pedigree analysis: parameter estimation and genotypic uncertainty

Many problems of sampling strategy arise in pedigree analysis. Although specific questions have been previously considered, there is a need for a general study of the form of the likelihood surface for genetic models. Were genotypes observable, the log-likelihood would have a very simple form. The two classes of factors of genealogical structure affecting general questions of inference are thus those (such as inbreeding or assortive mating) which affect the genotype distribution within a pedigree, and those affecting the extent to which these unobservable genotypes can be inferred from phenotypes. The latter aspect is considered in some detail.     

SPECIES CONCEPTS IN THE GENUSUSNEA(LICHENIZED ASCOMYCETES)

Practically most of the taxonomists working on vascular plants and fungi are using the so-called taxonomic species concept, relying largely on morphological criteria or other observable patterns of discontinuity and assuming that these patterns are reflecting the underlying genetic integrity of species. Such a concept is described in detail here for the genusUsnea. The typological view versus the populational view of species are discussed. The diagnostic value of characters used by previous and recent taxonomists of the genus is analysed. The fact thatUsneahas such a bad taxonomic reputation is discussed. The use by J. Motyka, author of the world monograph published in the thirties, of characters that are strongly modified by environmental factors together with a typological view of species are thought to be mainly responsible for this. More than 770 names have been published worldwide so far and it is suggested that around 50% are to be considered as synonyms.     

A model of evolution for accumulating genetic information

By taking into account recent knowledge of multigene families and other repetitive DNA sequences, a model of evolution by gene duplication for accumulating genetic information is studied. Genetic information is defined as the sum of distinct functions that the gene family can perform. A coefficient, "genetic diversity" is defined and used in this study, that is highly correlated with genetic information. Initially, a multigene family with a few gene copies is assumed, and natural selection starts to work on this gene family to increase genetic diversity contained in the gene family. As an important mechanism, unequal crossing-over is incorporated. Together with mutation, it is responsible for supplying genetic variability among individuals for selection to work. A specific model, in which individuals with less genetic diversity are selectively disadvantageous, has been studied in detail. Through approximate theoretical analysis and extensive Monte Carlo studies, it has been shown that the system is an extremely efficient way to accumulate genetic information. For attaining one gene, the genetic load is much smaller under this model than under the traditional model of natural selection. The model may be applied to the process of origin of multigene families with diverse copy members such as those of immunoglobulin or cytochrome P450. In general, the process of creating new genes by duplication might be somewhere between the present and the traditional models.     

A unified approach to joint modeling of multiple quantitative and qualitative traits in gene mapping

Using graph theory, we present a theoretical basis for mapping oligogenes in the joint presence of multiple phenotypic measurements of both quantitative and qualitative types. Various statistical models proposed earlier for several traits of solely single type are special cases of the unified approach given here. Our emphasis is on the generality of the framework, without specifying explicit assumptions about a sampling design. When information about environmental factors potentially affecting the traits is available, it can be incorporated into the genetic model. We adopt the Bayesian inferential machinery due to its firm theoretical basis and its capability of handling uncertain quantities; such as unobserved model parameters, missing marker data, and even different putative genetic models, probabilistically within a single framework. It is shown here that biological hypotheses about single gene affecting simultaneously multiple traits (pleiotropy) can be intuitively imposed as parameter constraints, leading to pleiotropic models for which posterior probabilities can be calculated. Outline of the possible implementation of the Bayesian method is described using the general reversible-jump Markov chain Monte Carlo algorithm. Some future challenges and extensions are also discussed.     

Analysis of the conformation of polypeptides : the combined use of energy computations and nuclear magnetic resonance studies.

This review surveys current approaches to the problem of determining the solution conformation of polypeptides. The basic principles of energy computations are described. The utility, problems, and limitations of various theoretical methods are summarized: conformational energy mapping, energy minimization, scanning of selected local conformations, statistical predictive schemes. The need for combining the calculations with experimental studies is pointed out. The information content of various physico-chemical methods is compared for this purpose. The analysis of nmr coupling constants is discussed in more detail. In combination with energy computations, it can furnish specific information on local aspects of the conformation. Examples of such combined studies on small peptides are summarized.     

Is the “Histone Code” an Organic Code?

Post-translational histone modifications and their biological effects have been described as a ‘histone code’. Independently, Barbieri used the term ‘organic code’ to describe biological codes in addition to the genetic code. He also provided the defining criteria for an organic code, but to date the histone code has not been tested against these criteria. This paper therefore investigates whether the histone code is a bona fide organic code. After introducing the use of the term ‘code’ in biology, the criteria a putative organic code such as the histone code must conform to in order to be recognised as an organic code are described. Our current knowledge of histones and their major post-translational modifications, and the specific protein binding domains that recognise and translate these into specific biological effects, is then reviewed in detail. The histone modification system is then placed in the context of an organic code and it is concluded that it fulfils all the requirements of an organic code. The marks produced on histones by processes such as acetylation and methylation act as organic signs that are translated into unique biological effects, their biological meanings. These translations are accomplished by effector proteins that consist of a binding domain that recognises a specific histone mark and a regulatory domain that mediates the biological effect. Crucially, these domains can be experimentally interchanged between different effector proteins, thus altering the rules that specify the relationships between sign and meaning. The effector proteins therefore fulfil the role of adaptor molecules.     

植物的交配系统与濒危植物的保护繁育策略

植物的交配系统在理论上被视为影响种群遗传结构最为显著的因素之一。在具体实践中,指导着遗传育种和濒危植物的保护。本文首先剖析了交配系统及其相关的概念,并简要回顾交配系统研究的历史、重要的理论模型和方法。然后说明交配系统与种群遗传结构的具体关系,进而讨论交配系统在濒危植物进化与适应中的作用。最后说明交配系统的信息在就地与迁地保护中的重要性。     

Complementary replication.

Differential equations for the kinetics of complementary replicating macromolecules in a flow reactor are derived. It is shown that such a model has many features in common with the differential equation for direct replication, the replicator equation. Two special cases of replication, and the influence of mutation on them, have been studied in detail. In the case of first-order mass action kinetics--the quasi-species model--complementary replication, like direct replication, exhibits an error threshold for the replication accuracy, below which the genetic information is lost. In turns out that the long-time behavior of many special cases of the second-order kinetics model can be described in terms of second-order replicator equations, although this is not possible in general.     

Structure of ethanol-inhibited porcine pepsin at 2-A resolution and binding of the methyl ester of phenylalanyl-diiodotyrosine to the enzyme

An account of x-ray crystallographic studies of monoclinic porcine pepsin crystals is presented. The chain fold specific for aspartyl proteases is described in detail. As the results of 2-A refinement have shown, the actual structure is that of ethanol-inhibited pepsin. The structure, although close to those of fungal aspartyl proteases, has some specific features: one of them is an insertion near the S'1 site which restricts the position of dipeptide substrates and makes their productive binding more probable than in the fungal enzymes. 3-A resolution data on the binding of the dipeptide phenylalanyl-diiodotyrosine methyl ester are discussed.     

Estimating genetic covariance functions assuming a parametric correlation structure for environmental effects

A random regression model for the analysis of "repeated" records in animal breeding is described which combines a random regression approach for additive genetic and other random effects with the assumption of a parametric correlation structure for within animal covariances. Both stationary and non-stationary correlation models involving a small number of parameters are considered. Heterogeneity in within animal variances is modelled through polynomial variance functions. Estimation of parameters describing the dispersion structure of such model by restricted maximum likelihood via an "average information" algorithm is outlined. An application to mature weight records of beef cow is given, and results are contrasted to those from analyses fitting sets of random regression coefficients for permanent environmental effects.     

A note on the quantum-theoretic basis of primary genetic activity

In previous work (Bull. Math. Biophysics,23, 393–403, 1960) it was shown that, if primary genetic processes are of an essentially microphysical nature, the objects bearing the primary genetic information must act in a catalytic fashion. At the same time it was pointed out that the kind of catalysis involved in the primary genetic process was fundamentally different, in specific ways, from that occurring, e.g., in enzyme systems. The present work demonstrates that, if the information-bearing objects of the general theory are identified with molecules of DNA, and the primary gene products are considered to be RNA of the “messenger” variety, then the predictions of the general theory can be compared with experimental data from various recently isolated polymerase systems, which appear to “copy” a sequence of nucleotides from DNA into RNAin vitro, and with certainin vivo microbial systems. It is found that these data provide detailed support for the conclusions drawn from the general theory. However, it is emphasized that the identification of the information-bearing objects and primary gene products as DNA and RNA respectively, which allows us to compare the theory with the cited data, is by no means the only identification which can be made; i.e., other interpretations of the general theory are certainly not precluded. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command, under Grant No. AF-AFOSR-9-63.     

DNA Codes and Information: Formal Structures and Relational Causes

Recently the terms "codes" and "information" as used in the context of molecular biology have been the subject of much discussion. Here I propose that a variety of structural realism can assist us in rethinking the concepts of DNA codes and information apart from semantic criteria. Using the genetic code as a theoretical backdrop, a necessary distinction is made between codes qua symbolic representations and information qua structure that accords with data. Structural attractors are also shown to be entailed by the mapping relation that any DNA code is a part of (as the domain). In this framework, these attractors are higher-order informational structures that obviate any "DNA-centric" reductionism. In addition to the implications that are discussed, this approach validates the array of coding systems now recognized in molecular biology.     

相关序列扩增多态性(SRAP)标记及其应用研究进展

SRAP是一项基于PCR技术的分子标记技术,利用其独特的引物设计对基因组的开放阅读框(ORFs)进行特异扩增,利用个体以及物种的内含子、启动子和间隔序列的不同,产生基于内含子和外显子的SRAP多态性。阐述了SRAP的原理和流程,详细论述了SRAP标记目前在植物遗传多样性、作物品种鉴定、遗传图谱构建等方面的研究进展及应用前景。     

8. Molecular biology and genetic conservation programmes

The techniques of molecular biology will become a standard part of germplasm conservation and exploitation. They are being used to gather information very rapidly about chromosome structure and genetic variation within the major crop species. Genetic maps with hundreds of DNA sequence markers covering the whole genome have already been created for some crops, such as maize, soybean, wheat and potato. Genetic variation is being revealed by the combined use of restriction endonucleases, fractionation of DNA fragments by electrophoresis and investigation of the size of specific allelic fragments. This kind of approach offers new opportunities to assess the extent of genetic variation among accessions in germplasm collections, thereby helping to decide which accessions are essentially duplicates and which should be maintained in a core collection. I recommend that germplasm banks will in the future also contain diagnostic DNA markers for characterizing and screening germplasm.
When material from germplasm banks is used in crop plant breeding programmes to transfer specific traits into the crop, the availability of a complete set of molecular markers covering the entire genome makes it straightforward to discover which segments have been transferred and which are essential to maintain, so as to preserve the introduced trait.
Germplasm banks are obviously a source of new genetic variation for the molecular geneticist as well as the plant breeder. The isolation of specific alleles determining self-incompatibility from Brassica oleracea accessions for subsequent introduction into oil seed rape is described as an example.     

Testing separate families of segregation hypotheses: bootstrap methods.

Aspects of the statistical modeling and assessment of hypotheses concerning quantitative traits in genetics research are discussed. It is suggested that a traditional approach to such modeling and hypothesis testing, whereby competing models are "nested" in an effort to simplify their probabilistic assessment, can be complimented by an alternative statistical paradigm - the separate-families-of-hypotheses approach to segregation analysis. Two bootstrap-based methods are described that allow testing of any two, possibly non-nested, parametric genetic hypotheses. These procedures utilize a strategy in which the unknown distribution of a likelihood ratio-based test statistic is simulated, thereby allowing the estimation of critical values for the test statistic. Though the focus of this paper concerns quantitative traits, the strategies described can be applied to qualitative traits as well. The conceptual advantages and computational ease of these strategies are discussed, and their significance levels and power are examined through Monte Carlo experimentation. It is concluded that the separate-families-of-hypotheses approach, when carried out with the methods described in this paper, not only possesses some favorable statistical properties but also is well suited for genetic segregation analysis.     

Periodic metabolic systems: Oscillations in multiple-loop negative feedback biochemical control networks

Summary For a general multiple loop feedback inhibition system in which the end product can inhibit any or all of the intermediate reactions it is shown that biologically significant behaviour is always confined to a bounded region of reaction space containing a unique equilibrium. By explicit construction of a Liapunov function for the general n dimensional differential equation it is shown that some values of reaction parameters cause the concentration vector to approach the equilibrium asymptotically for all physically realizable initial conditions. As the parameter values change, periodic solutions can appear within the bounded region. Some information about these periodic solutions can be obtained from the Hopf bifurcation theorem. Alternatively, if specific parameter values are known a numerical method can be used to find periodic solutions and determine their stability by locating a zero of the displacement map. The single loop Goodwin oscillator is analysed in detail. The methods are then used to treat an oscillator with two feedback loops and it is found that oscillations are possible even if both Hill coefficients are equal to one.