Biomedical subjects
Publications and source records attributed to M F Macchiato.
A statistical method for characterizing nucleotidic sequences based on maximum entropy techniques is presented. The method uses only codon usage tables and takes into account the length of sequences, and preserves the information contained in each codon by a punctual index. We present the methodological aspects of the analysis, showing an application relative to nucleotidic sequences of eukaryotes.
VARIANT, a FORTRAN 77 computer system for storing and retrieving the amino acid replacements in human haemoglobin variants on a multicriterion basis, is presented. The system is transportable and user-friendly, can easily be expanded and can also be used to create a database of the amino acid replacements in families of homologous proteins, becoming an efficient tool for evolutionary studies.
A real-time, machine-independent software for the analysis and manipulation of sequence data is described. The implemented system allows users to read in sequence data from existing data bases, and to edit, manipulate, analyse and align them. It is easy to use and is suitable for routine investigations and to modify sequences in order to create a user customized data base.
An algorithm to determine the probability that a reading frame codifies for a protein is presented. It is based on the results of our previous studies on the thermodynamic characteristics of a translated reading frame. We also develop a prediction procedure to distinguish between coding and non-coding reading frames. The procedure is based on the characteristics of the putative product of the DNA sequence and not on periodicity characteristics of the sequence, so the prediction is not biased by the presence of overlapping translated reading frames or by the presence of translated reading frames on the complementary DNA strand.
A statistical analysis of the autocorrelation characteristics of active polypeptides has been carried out by means of the correlogram method. It is shown that the amino acid sequences of the analysed proteins, considered as a whole, are autocorrelated and that the correlograms characterize each protein reflecting its three-dimensional structure.
Two independent methods are used to evaluate the protein-coding information content in different classes of DNA sequences. The first method allows to evaluate the statistical relevance of finding unidentified reading frames, longer than 100 codons, on both DNA strands of: a) 117 DNA sequences that code for 142 nuclear proteins; b) 39 stable RNA coding sequences and c) 36 other DNA sequences which include regulatory and as yet unknown function sequences. The finding of 50 reading frames longer than 100 codons (complementary inverted proteins or c.i.p. genes) located on the DNA strand complementary to the protein-coding one is drastically in excess of the number predicted by chance alone. An independent method (testcode) applied to c.i.p. gene sequences, which assigns the probability of coding to a given sequence, predicts that more than 50% of these genes are translated in a functional product. These analyses indicate the existence of a new class of protein-coding genes, located on the DNA sequences complementary to the protein-coding DNA strand.
Computer programs, implemented on an Univac II00/80 computer system, for the identification and characterization of protein coding genes and for the analysis of nucleic acid sequences, are described.
Mean doses for damage induced by 3.7-MeV protons in T4 phage were measured for the following effects: inactivation, killing, adsorption, DNA injection, capsid rupture with DNA release, and single- and double-strand DNA breaks. These effects have been related to phage survival in the same experiment because of the variability inherent in such measurements. The experiments were carried out in nutrient broth, phosphate buffer, and phosphate buffer plus histidine as suspension media. The following conclusions can be drawn: (i) DNA double-strand breakage is the dominant cause of inactivation in nutrient broth; (ii) scavengers protect the DNA inside the capsid to only a small degree; (iii) indirect actions affect functions associated with proteins; (iv) DNA release, as measured by capsid rupture, accounts for only a small percentage of the loss of viability; (v) essentially all DNA from adsorbed phage is injected even though a large proportion of the DNA contains double-strand breaks.
One of the distinctive features of a biological system is its remoteness from equilibrium: for the treatment of the information exchanged by these systems with the external world the concept of information amount is not sufficient because for nonequilibrium systems we need further specifications about information, i.e. its value. We defined the information value for a genetic code. The comparison of the results we had applying such a definition to the three genetic codes found in nature shows that our definition described the system of transmission and reception of information in a biological organism very well and that the information value of a genetic code can be considered as an index of its efficiency, i.e. of its ability to minimize the effects of a mutation of the genotype on the phenotype. Otherwise, our results show that the information value, and hence the efficiency of the three known codes is the same and suggest that the prerequisite of the evolution of the codes is the preservation of this value.
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The Montecarlo method is used to computer simulate a random distribution of molecular lengths generated by inducing T4 DNA fragmentation through the decay of 32P atoms introduced in the molecule. Taking into account the experimental conditions we find that the value of alpha for alkali sucrose gradients is 0.46 +/- 0.02 and does not depend on the running time. Our findings also prove that the computer simulation can be utilized to analyze sedimentation profiles of DNA molecules fragmented in vivo.
The partial-denaturation map of T4 DNA is obtained by using benzyldodecyldimethyl ammonium chloride in the presence of a high concentration of formamide. In this way suitable conditions for preparation of electron microscope specimens and partial denaturation within a temperature range low enough to minimize the endonucleolytic cleavage, are realized. It is found that, under our experimental conditions, the denaturation increase depends mainly on the appearance of new denaturation sites rather than on the lengthening of DNA segments already denatured. Because of the DNA circular permutation it is necessary to align the measured maps to obtain the denaturation pattern. This is done through a computer program and informations on the distribution of the regions with highest (A-T) content along the genome are obtained. The results of contour length measurements of lambda and T4 DNA's are also reported.
Phage T4 is known to have a linear duplex chromosome that is circularly permuted and terminally repeated. We found, by denaturation and self-reannealing experiments, that circular permutation in T4 native DNA is not random. Their multimodal distribution of permutation is compatible with the "headful packaging" model with the additional specifications that the encapsulation of DNA starts at several sites and these are not random distributed.