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M Eigen

Publications and source records attributed to M Eigen.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of the envelope region of the highly divergent HIV-2ALT isolate extends the known range of variability within the primate immunodeficiency viruses.

HIV-2ALT is a highly divergent HIV-2-related isolate that is genetically equidistant to the prototypic HIV-2 strains, defined by HIV-2ROD, and to the simian immunodeficiency viruses SIVmac and SIVsm. We have now cloned and sequenced the envelope region of HIV-2ALT, thus completing the analysis of the whole viral genome. The sequences of env and nef and of the second exons of tat and rev were compared with those of the other viruses of the HIV-2/SIVsm/SIVmac group. Despite of the high degree of variation of HIV-2ALT, functional domains of the genes are conserved. Although in env, the overall pattern of constant and variable domains is maintained, many single amino acid exchanges exist at positions previously thought to be constant in HIV-2 strains. In addition, when compared with a broader spectrum of immunodeficiency viruses, which includes SIVMND from mandrill and SIVAGM from African green monkey, HIV-2ALT Env has a high percentage of amino acid exchanges, which are unique to this strain. This underlines the separate branch of HIV-2ALT within the phylogenetic tree and makes obvious the inclusion of such divergent strains in preventive and therapeutic programs.

Amino Acid Sequence↗
PubMed1990

A novel proviral clone of HIV-2: biological and phylogenetic relationship to other primate immunodeficiency viruses.

Infectious molecular clones of the human immunodeficiency virus type 2 (HIV-2) will be valuable tools for the study of regulatory gene functions and the development of an animal model for the human acquired immunodeficiency syndrome (AIDS). To this end, we have cloned and sequenced a novel HIV-2 isolate, HIV-2BEN. One clone, designated MK6, is infectious for various human T-cell lines and for human and macaque peripheral blood lymphocytes (PBL), allowing molecular studies of HIV-2 infection and replication. Since MK6 is highly cytopathic in MT-2 and Molt-4 clone 8 cells, antiviral agents and neutralizing sera may be tested. Cluster analysis of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) env and gag genes revealed that HIV-2BEN yielded the earliest node of phylogenetic divergence for all reported HIV-2 sequences. Noise analysis showed that, with the current data, no specification of any branching order can be made among the four groups of primate lentiviruses, HIV-1, HIV-2/SIVSMM/MAC, SIVAGM, and SIVMND.

Animals↗
PubMed1989

How old is the genetic code? Statistical geometry of tRNA provides an answer.

The age of the molecular organization of life as expressed in the genetic code can be estimated from experimental data. Comparative sequence analysis of transfer RNA by the method of statistical geometry in sequence space suggests that about one-third of the present transfer RNA sequence divergence was present at the urkingdom level about the time when archaebacteria separated from eubacteria. It is concluded that the genetic code is not older than, but almost as old as our planet. While this result may not be unexpected, it was not clear until now that interpretable data exist that permit inferences about such early stages of life as the establishment of the genetic code.

Anticodon↗
PubMed1989

The AIDS debate.

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Acquired Immunodeficiency Syndrome↗
PubMed1988

Statistical geometry in sequence space: a method of quantitative comparative sequence analysis.

A statistical method of comparative sequence analysis that combines horizontal and vertical correlations among aligned sequences is introduced. It is based on the analysis mainly of quartet combinations of sequences considered as geometric configurations in sequence space. Numerical invariants related to relative internal segment lengths are assigned to each such configuration and statistical averages of these invariants are established. They are used for internal calibration of the topology of divergence and for quantitative determination of the noise level. Comparison of computer simulations with experimental data reveals the high sensitivity of assignment of basic topologies even if much randomized. In addition, these procedures are checked by vertical analysis of the aligned sequences to allow the study of divergences with positionally varying substitution probabilities.

Base Sequence↗
PubMed1985

Kinetics of RNA replication: competition and selection among self-replicating RNA species.

The process of Darwinian selection in the self-replication of single-stranded RNA by Q beta replicase was investigated by analytical and computer-simulation methods. For this system, the relative population change of the competing species was found to be a useful definition of selection value, calculable from measurable kinetic parameters and concentrations of each species. Critical differences in the criteria for selection were shown to pertain for replicase/RNA ratios greater than or less than 1, for the case that formation of double-stranded RNA occurs and when comparisons are made of closed with open systems. At a large excess of enzyme, RNA species grow exponentially without interfering with each other, and selection depends only on the fecundity of the species, i.e., their overall replication rates. For RNA concentrations greater than the replicase concentration, the selection of species is governed by their abilities to compete for enzyme. Under conditions where formation of double strands occurs, competition leads to a coexistence of the species; the selection values vanish, and the concentration ratios depend only on the template binding and double-strand formation rates. The approach to coexistence is rapid, because when its competitors are in a steady state, a species present in trace amount is amplified exponentially. When formation of hybrid double strands occurs at a substantial rate, coexistence of hybridizing species is essentially limited to cases where the formation rate of heterologous double strands is smaller than the geometric mean of the formation rates of the homologous double strands. At limiting cases, e.g. in the steady states, simple analytical expressions for the main aspects of the selection process were found. Experimental data support the analytical expressions and the simulations.

Computers↗
PubMed1985

[Epidemiology of AIDS].

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Acquired Immunodeficiency Syndrome↗
PubMed1985

Pattern analysis of 5S rRNA.

Some 200 different 5S rRNA sequences from eubacteria, chloroplasts, mitochondria, archaebacteria, and eukaryotes were analyzed for evolutionary kinship relationships and associated sequential features. Group-specific occupation schemes for the 149 positions of an overall alignment were established. Eubacterial, archaebacterial, and intermediate occupation schemes all yield a strongly biased base triplet pattern in one of the three possible reading frames strongest for eubacterial, chloroplastic, and archaebacterial, but still detectable for mitochondrial and eukaryotic cytoplasmic sequences. The frequency of triplets decays in the order RNY greater than RNR greater than YNY greater than YNR; R being a purine (guanine or adenine), Y is a pyrimidine (cytosine or uracil), and N is any base. A strong preference for guanine or cytosine was found in all triplet positions. The effects show no exceptions and are clearly above the level of statistical fluctuations.

Archaea↗
PubMed1985

Toward Bion's starting point: between catastrophe and faith.

Catastrophe and faith are explored as the most basic terms of Bion's work. In doing so it is shown how Bion gets underneath Kleinian concepts to expand the depth phenomenology of a catastrophic sense of origins. For Bion the self is born, evolves and dissolves with a sense of catastrophe. Whether or not Bion is right in various aspects of his account, catastrophe is an elemental term of our existence. For Bion, Faith is a proper primordial and developed response to catastrophe. This paper discusses aspects of the relationship between faith, knowledge, container-contained and catastrophe.

Defense Mechanisms↗
PubMed1979

Selection and self-organization of self-reproducing macromolecules under the constraint of constant flux.

We investigate the dynamic behavior of a set of self-reproducing macromolecules (e.g., polynucleotides) under conditions such that the fluxes of all monomer units into the system are kept constant. Such conditions might prevail in an evolution reactor or in certain naturally occurring situations. A general set of equations is developed to describe the behavior of both the macromolecule and the monomer concentrations. The question of how the rate of macromolecule synthesis varies with the monomer levels is discussed briefly. With the help of several physically reasonable approximations, we obtain an exact solution for a simplified constant flux system. Comparison with the corresponding system under the constraint of constant overall organization reveals important similarities, most notably in the existance and composition of quasispecies. Given the same set of physical and chemical parameters, a system subject to constant flux will always evolve toward selective equilibrium more slowly than under the constraint of constant organization.

Kinetics↗