Search PubMedSearch

Biomedical subjects

M Schöniger

Publications and source records attributed to M Schöniger.

9 recordsLinked to original sources

Evolution of DNA or amino acid sequences with dependent sites.

A framework is outlined to study the evolution of DNA or amino acid sequences, if sequence sites do not evolve independently. The units of evolution are nonoverlapping subsequences of length l. Each subsequence evolves independently of the others, but within a subsequence the sequences show a Markov order one dependency. We describe an algorithm to mimic the evolution of such sequences. The influence of dependencies between sites on distance estimates and the reliability of tree reconstruction methods is investigated. We show that an inappropriate model of sequence evolution in the tree reconstruction process will lead to a nonempty Felsenstein zone. Finally, we describe a method to infer l from sequence data. Examples from the evolution of DNA sequences as well as from amino acids are given.

Algorithms

DISTREE: a tool for estimating genetic distances between aligned DNA sequences.

MOTIVATION: Substitution rates estimated from aligned DNA data can be used as genetic distances to investigate the phylogenetic relationship of those sequences. For this purpose, a Markov model of nucleotide substitution has to be assumed that describes this process most adequately. RESULTS: A program is presented that estimates substitution rates and their standard errors for a variety of Markov models. The model introduced by Hasegawa et al. (J. Mol. Evol., 22, 160-174, 1985) is the only one for which distances and standard deviations need to be calculated numerically, since analytical formulae cannot be derived. Each model is implemented in two different variants: (i) assuming rate homogeneity or (ii) starting from Gamma-distributed substitution rates across sequence sites. The estimation of heterogeneous substitution rates is based on a method suggested by Tamura and Nei (Mol. Biol. Evol., 10, 512-526, 1993). All required parameters are estimated from sequence data, hence the user is not asked to supply any additional input. One goal of the program is to support the user when choosing a particular model that describes most adequately the evolution of the given data set. For this purpose, a more detailed analysis of this model fit is provided. Phylogenetic trees reconstructed from the inferred distances using the neighbor-joining algorithm are also available.

Algorithms

[Telemetry during swimming in risk evaluation of heart patients in rehabilitation].

Swimming differs from other forms of exercise due to its additional hydrostatic and thermal burden. It was investigated whether additional pathologic findings in comparison to history and standard exercise tests can be obtained by holter monitoring during swimming. Symptoms and exercise electrocardiogram were compared with the holter ECG during swimming in 125 patients divided into 3 groups with different diagnoses and severity of cardiac diseases. In a considerable percentage of patients ischemic changes and severe rhythm disturbances were found only during swimming with further diagnostic and therapeutic consequences, though patients with moderate and severe angina and with significant ischemic signs in the exercise test were excluded and mainly patients with slight or absent symptoms were evaluated predominantly. Thus, since swimming is a favorite leisure-time occupation also in patients with diseases of heart and circulation, holter monitoring during swimming is of diagnostic importance in the rehabilitation of these patients.

Adult

Complementary coding conforms to the primeval comma-less code.

The hypothesis that the universal genetic code is adapted to double-strand coding is supported by its remarkable compatibility with the RNY comma-less hypothesis. Coding by a triplet code on a polynucleotide double-strand allows for enciphering of five additional messages with reference to a chosen primary reading frame. Assuming the acceptance of coupled mutations on both strands, the best codon register for two overlapping messages can be inferred. The idea of evolutionarily compatible coding of two proteins by one nucleotide double-strand is extended to complementary coding for one protein in folded, single-stranded RNA.

Animals

Simulating efficiently the evolution of DNA sequences.

Two menu-driven FORTRAN programs are described that simulate the evolution of DNA sequences in accordance with a user-specified model. This general stochastic model allows for an arbitrary stationary nucleotide composition and any transition-transversion bias during the process of base substitution. In addition, the user may define any hypothetical model tree according to which a family of sequences evolves. The programs suggest the computationally most inexpensive approach to generate nucleotide substitutions. Either reproducible or non-repeatable simulations, depending on the method of initializing the pseudo-random number generator, can be performed. The corresponding options are offered by the interface menu.

Algorithms

A stochastic model for the evolution of autocorrelated DNA sequences.

Currently used stochastic models of DNA sequence evolution assume independent and identically distributed nucleotide sites. They are too simple to account for dependence structures obviously present in molecular data. Up to now more realistic stochastic models for nucleotide substitutions have been considered intractable. In this paper a procedure that accounts for non-overlapping correlations among pairs of sites of a DNA sequence is developed. We show that currently used models that ignore correlated sites underestimate distances inferred from observed sequence dissimilarities. For the analyzed mitochondrial sequence data this underestimation is not drastic in contrast to paired regions (stems) of bacterial 23S rRNA sequences.

Animals

Neutral adaptation of the genetic code to double-strand coding.

We lay new foundations to the hypothesis that the genetic code is adapted to evolutionary retention of information in the antisense strands of natural DNA/RNA sequences. In particular, we show that the genetic code exhibits, beyond the neutral replacement patterns of amino acid substitutions, optimal properties by favoring simultaneous evolution of proteins encoded in DNA/RNA sense-antisense strands. This is borne out in the sense-antisense transformations of the codons of every amino acid which target amino acids physicochemically similar to each other. Moreover, silent mutations in the sense strand generate conservative ones in its antisense counterpart and vice versa. Coevolution of proteins coded by complementary strands is shown to be a definite possibility, a result which does not depend on any physical interaction between the coevolving proteins. Likewise, the degree to which the present genetic code is dedicated to evolutionary sense-antisense tolerance is demonstrated by comparison with many randomized codes. Double-strand coding is quantified from an information-theoretical point of view.

Adaptation, Biological

A local algorithm for DNA sequence alignment with inversions.

A dynamic programming algorithm to find all optimal alignments of DNA subsequences is described. The alignments use not only substitutions, insertions and deletions of nucleotides but also inversions (reversed complements) of substrings of the sequences. The inversion alignments themselves contain substitutions, insertions and deletions of nucleotides. We study the problem of alignment with non-intersecting inversions. To provide a computationally efficient algorithm we restrict candidate inversions to the K highest scoring inversions. An algorithm to find the J best non-intersecting alignments with inversions is also described. The new algorithm is applied to the regions of mitochondrial DNA of Drosophila yakuba and mouse coding for URF6 and cytochrome b and the inversion of the URF6 gene is found. The open problem of intersecting inversions is discussed.

Algorithms

Stochastic traits of molecular evolution--acceptance of point mutations in native actin genes.

A stochastic matrix of nucleotide mutation probabilities is derived by counting differences and identities in alignments of native actin genes, with the aim of obtaining a more reliable data base for regular modes of molecular evolution. The evolution of DNA sequences is thereby considered as a Markov process consisting of events (point mutations) characterized by a stochastic matrix for codon-codon interchanges. The genetic distance is set to 1 PAM (percentage of accepted point mutations). The results can be reproduced by Monte Carlo simulations which are subjected to selective constraints. The latter are observed as nonrandom codon usage and ratios of silent to recognizable point mutations. Specific patterns within the matrix of mutation probabilities attest to preferences of natural selection in the evolution of a specific protein.

Actins