Formal Darwinism

Two questions are raised for Grafen’s formal darwinism project of aligning evolutionary dynamics under natural selection with the optimization of phenotypes for individuals of a population. The first question concerns mean fitness maximization during frequency-dependent selection; in such selection regimes, not only is mean fitness typically not maximized but it is implausible that any parameter closely related to fitness is being maximized. The second question concerns whether natural selection on inclusive fitness differences can be regarded as individual selection or whether it leads to a departure from the central motivation that led to the formal darwinism project, viz., to show that “Darwinian” evolution through individual selection leads to “good design” or phenotypic adaptation through trait optimization.     

Formal Genetics of Ascidians

SYNOPSIS. Our knowledge of ascidian genetics is reviewed. Thepaper is primarily concerned with the author's past and currentwork on the colonial species Bolryllus schlosseri. Five Mendelianloci account for most of its impressive polychromatism. Breedingexperiments have substantiated the hypothesis of a single multialleliclocus for each of three enzymes (MDH, SOD, PGI) suggested byelectrophoretic patterns. The nuclei of three linkage groupshave been revealed. Self—fertilization entails a severeinbreeding depression. A specific self, nonself recognition,expressed by fusion or repulsion of contacting colonies, occursin this species also. At variance with Botryllus primigenus,fusible colonies of B. schlosseri are completely interfertile.This has allowed a more direct genetic analysis of the phenomenon,confirming the alleged control by a single multiallelic locus.In order to fuse, the confronted colonies must share at leastone allele. Young buds grafted in the tunic after removal ofall the zooids develop a new colony at the host's expense onlyif donor and host are fusible. This means that fusibility andhistocompatibility are strictly correlated. Chimerical colonies,obtained either in this way or following the resorption of oneof two fused colonies, are now being investigated for theirrecognition specificity and electrophoretic pattern. Preliminarydata indicate that both can be durably altered, suggesting thatthe allogeneic cell populations are persistent and renewing.     

Formal Methods for Hopfield-Like Networks

Building a meaningful model of biological regulatory network is usually done by specifying the components (e.g. the genes) and their interactions, by guessing the values of parameters, by comparing the predicted behaviors to the observed ones, and by modifying in a trial-error process both architecture and parameters in order to reach an optimal fitness. We propose here a different approach to construct and analyze biological models avoiding the trial-error part, where structure and dynamics are represented as formal constraints. We apply the method to Hopfield-like networks, a formalism often used in both neural and regulatory networks modeling. The aim is to characterize automatically the set of all models consistent with all the available knowledge (about structure and behavior). The available knowledge is formalized into formal constraints. The latter are compiled into Boolean formula in conjunctive normal form and then submitted to a Boolean satisfiability solver. This approach allows to formulate a wide range of queries, expressed in a high level language, and possibly integrating formalized intuitions. In order to explore its potential, we use it to find cycles for 3-nodes networks and to determine the flower morphogenesis regulatory network of Arabidopsis thaliana. Applications of this technique are numerous and concern the building of models from data as well as the design of biological networks possessing specified behaviors.     

Polyelectrolyte Charge Corrected Molecular Weight and Effective Charge by Sedimentation

Ionic charge on a macromolecule complicates the determination of its molecular weight in solution due to the Donnan effect. Compensation for it can be made if one knows the value of the effective charge, which can be found by dialysis equilibrium across a semipermeable membrane. A moving boundary of molecules sedimenting in a centrifugal field can act as a membrane, obviating some of the disadvantages (such as selective adsorption) of a real membrane. Interference optics are used to monitor the reverse gradient of the salt due to the Donnan effect, hence facilitating the determination of the effective charge. The apparent molecular weight obtained from a conventional sedimentation equilibrium can then be corrected to yield the true molecular weight. The effective charge is valuable in revealing macromolecular structural features when related to the titratable charge through the Manning counter-ion condensation theory. Agreement between the values of the backbone molecular weights for the Na, Cs, and Ca salts of heparin indicated the validity of the approach. The effective charge ratio and the axial charge spacing for the Na and Ca heparin agreed with the literature, whereas the results for Cs indicated a degree of binding in excess of that due to counter-ion condensation.     

Charge transport in B-carotene

The absorption currents in the ‘cis-trans’ isomeric forms of β-carotene glass were studied over a wide range of temperature and field. Limited observations of the absorption currents were also made with different sample thicknesses and electrode materials. The results indicate that the low temperature absorption current (<273K) may be due to a dipolar mechanism with a distribution of relaxation times whereas the absorption current in the high temperature range (≃273K<T<333K) may be adequately explained by a hopping mechanism of charge carriers through the localized states distributed by the bulk.     

Charge transport in DNA

The base pair stack within double helical DNA provides an effective medium for charge transport. The DNA pi-stack mediates oxidative DNA damage over long molecular distances in a reaction that is exquisitely sensitive to the sequence-dependent conformation and dynamics of DNA. A mixture of tunneling and hopping mechanisms have been proposed to account for this long-range chemistry, which is gated by dynamical variations within the stack. Electrochemical sensors have also been developed, based upon the sensitivity of DNA charge transport to base pair stacking, and these sensors provide a completely new approach to diagnosing single base mismatches in DNA and monitoring protein-DNA interactions electrically. DNA charge transport, furthermore, may play a role within the cell and, indeed, oxidative damage to DNA from a distance has been demonstrated in the cell nucleus. As a result, the biological consequences of and opportunities for DNA-mediated charge transport now require consideration.