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Biomedical subjects

S A Kauffman

Publications and source records attributed to S A Kauffman.

7 recordsLinked to original sources

Coevolution to the edge of chaos: coupled fitness landscapes, poised states, and coevolutionary avalanches.

We introduce a broadened framework to study aspects of coevolution based on the NK class of statistical models of rugged fitness landscapes. In these models the fitness contribution of each of N genes in a genotype depends epistatically on K other genes. Increasing epistatic interactions increases the rugged multipeaked character of the fitness landscape. Coevolution is thought of, at the lowest level, as a coupling of landscapes such that adaptive moves by one player deform the landscapes of its immediate partners. In these models we are able to tune the ruggedness of landscapes, how richly intercoupled any two landscapes are, and how many other players interact with each player. All these properties profoundly alter the character of the coevolutionary dynamics. In particular, these parameters govern how readily coevolving ecosystems achieve Nash equilibria, how stable to perturbations such equilibria are, and the sustained mean fitness of coevolving partners. In turn, this raises the possibility that an evolutionary metadynamics due to natural selection may sculpt landscapes and their couplings to achieve coevolutionary systems able to coadapt well. The results suggest that sustained fitness is optimized when landscape ruggedness relative to couplings between landscapes is tuned such that Nash equilibria just tenuously form across the ecosystem. In this poised state, coevolutionary avalanches appear to propagate on all length scales in a power law distribution. Such avalanches may be related to the distribution of small and large extinction events in the record.

Biological Evolution

Drosophila segmentation: supercomputer simulation of prepattern hierarchy.

Spontaneous prepattern formation in a two level hierarchy of reaction-diffusion systems is simulated in three space co-ordinates and time, mimicking gap gene and primary pair-rule gene expression. The model rests on the idea of Turing systems of the second kind, in which one prepattern generates position dependent rate constants for a subsequent reaction-diffusion system. Maternal genes are assumed responsible for setting up gradients from the anterior and posterior ends, one of which is needed to stabilize a double period prepattern suggested to underly the read out of the gap genes. The resulting double period pattern in turn stabilizes the next prepattern in the hierarchy, which has a short wavelength with many characteristics of the stripes seen in actual primary pair-rule gene expression. Without such hierarchical stabilization, reaction-diffusion mechanisms yield highly patchy short wave length patterns, and thus unreliable stripes. The model yields seven stable stripes located in the middle of the embryo, with the potential for additional expression near the poles, as observed experimentally. The model does not rely on specific chemical reaction kinetics, rather the effect is general to many such kinetic schemes. This makes it robust to parameter changes, and it has good potential for adapting to size and shape changes as well. The study thus suggests that the crucial organizing principle in early Drosophila embryogenesis is based on global field mechanisms, not on particular local interactions.

Animals

Control of sequential compartment formation in Drosophila.

During development of Drosophila melanogaster, sequential commitment to alternative development programs occurs in neighboring groups of cells. These commitments appear to be reflected by lines of clonal restriction, called compartmental boundaries, which progressively subdivide the early embryo, and later the imaginal discs, which give rise to different adult appendages. We propose that a reaction-diffusion system acts throughout development and generates a sequence of differently shaped chemical patterns. These patterns account for the sequence and geometries of compartmental boundaries, and predict that each terminal compartment is specifiied by a unique combination of binary choices made during its formation. This binary "code" interprets coherently the patterned metaplasia seen in transdetermination and homeotic mutations.

Animals

Premature replication of late S period DNA regions in early S nuclei transferred to late S cytoplasm by fusion in Physarum polycephalum.

Fusion of a late S period plasmodium of Physarum polycephalum to an early S period plasmodium causes premature replication of late S replicating regions in the nuclei of the early S plasmodium. The extent of ahead-of-schedule replication of late S replicating regions in early S period nuclei increases to a plateau of 16-20% for fusions with 40-70 min of phase difference, then declines for larger phase differences. The stimulatory factors for late S replicative units are present only in late S plasmodia and appear to act only on late S regions. Once replicated, early S replicating regions are not stimulated to replicate again by fusion to a plasmodium entering the S period. Our data do not discriminate between anti-termination of replication by factors of stop sites on long replicons, and a sequential initiation of replication on new, possibly non-adjacent regions, but does provide evidence that the stimulatory factors are distinct from one another and specific for certain target replicative units.

Cell Division