The Value of Moderate Obsession: Insights from a New Model of Organizational Search

This study presents a new model of search on a “rugged landscape,” which employs modeling techniques from fractal geometry rather than the now-familiar NK modeling technique. In our simulations,firms search locally in a two-dimensional fitness landscape, choosing moves in a way that responds both to local payoff considerations and to a more global sense of opportunity represented by a firm-specific “preferred direction.” The latter concept provides a very simple device for introducing cognitive or motivational considerations into the formal account of search behavior, alongside payoff considerations. After describing the objectives and the structure of the model, we report a first experiment which explores how the ruggedness of the landscape affects the interplay of local payoff and cognitive considerations (preferred direction) in search. We show that an intermediate search strategy, combining the guidance of local search with a moderate level of non-local “obsession,” is distinctly advantageous in searching a rugged landscape. We also explore the effects of other considerations, including the objective validity of the preferred direction and the degree of dispersion of firm strategies. We conclude by noting available features of the model that are not exercised in this experiment. Given the inherent flexibility of the model, the range of questions that might potentially be explored is extremely large.Rugged Landscapes; Local Search; Cognition; Obsession; Fractal Geometry

Genotype networks of 80 quantitative Arabidopsis thaliana phenotypes reveal phenotypic evolvability despite pervasive epistasis

We study the genotype-phenotype maps of 80 quantitative phenotypes in the model plant Arabidopsis thaliana, by representing the genotypes affecting each phenotype as a genotype network. In such a network, each vertex or node corresponds to an individual’s genotype at all those genomic loci that affect a given phenotype. Two vertices are connected by an edge if the associated genotypes differ in exactly one nucleotide. The 80 genotype networks we analyze are based on data from genome-wide association studies of 199 A. thaliana accessions. They form connected graphs whose topography differs substantially among phenotypes. We focus our analysis on the incidence of epistasis (non-additive interactions among mutations) because a high incidence of epistasis can reduce the accessibility of evolutionary paths towards high or low phenotypic values. We find epistatic interactions in 67 phenotypes, and in 51 phenotypes every pairwise mutant interaction is epistatic. Moreover, we find phenotype-specific differences in the fraction of accessible mutational paths to maximum phenotypic values. However, even though epistasis affects the accessibility of maximum phenotypic values, the relationships between genotypic and phenotypic change of our analyzed phenotypes are sufficiently smooth that some evolutionary paths remain accessible for most phenotypes, even where epistasis is pervasive. The genotype network representation we use can complement existing approaches to understand the genetic architecture of polygenic traits in many different organisms

Complexity Studies of Firm Dynamics

abstract: This thesis consists of three projects employing complexity economics methods to explore firm dynamics. The first is the Firm Ecosystem Model, which addresses the institutional conditions of capital access and entrenched competitive advantage. Larger firms will be more competitive than smaller firms due to efficiencies of scale, but the persistence of larger firms is also supported institutionally through mechanisms such as tax policy, capital access mechanisms and industry-favorable legislation. At the same time, evidence suggests that small firms innovate more than larger firms, and an aggressive firm-as-value perspective incentivizes early investment in new firms in an attempt to capture that value. The Ecological Firm Model explores the effects of the differences in innovation and investment patterns and persistence rates between large and small firms. The second project is the Structural Inertia Model, which is intended to build theory around why larger firms may be less successful in capturing new marketshare than smaller firms, as well as to advance fitness landscape methods. The model explores the possibility that firms with larger scopes may be less effective in mitigating the costs of cooperation because conditions may arise that cause intrafirm conflicts. The model is implemented on structured fitness landscapes derived using the maximal order of interaction (NM) formulation and described using local optima networks (LONs), thus integrating these novel techniques. Finally, firm dynamics can serve as a proxy for the ease at which people can voluntarily enter into the legal cooperative agreements that constitute firms. The third project, the Emergent Firm model, is an exploration of how this dynamic of voluntary association may be affected by differing capital institutions, and explores the macroeconomic implications of the economies that emerge out of the various resulting firm populations.Dissertation/ThesisDoctoral Dissertation Applied Mathematics for the Life and Social Sciences 201

Biological Evolution and Statistical Physics

This review is an introduction to theoretical models and mathematical calculations for biological evolution, aimed at physicists. The methods in the field are naturally very similar to those used in statistical physics, although the majority of publications appeared in biology journals. The review has three parts, which can be read independently. The first part deals with evolution in fitness landscapes and includes Fisher's theorem, adaptive walks, quasispecies models, effects of finite population sizes, and neutral evolution. The second part studies models of coevolution, including evolutionary game theory, kin selection, group selection, sexual selection, speciation, and coevolution of hosts and parasites. The third part discusses models for networks of interacting species and their extinction avalanches. Throughout the review, attention is paid to giving the necessary biological information, and to pointing out the assumptions underlying the models, and their limits of validity.Comment: Review article accepted for publication in Advances in Physics. 106 page

Machine Learning Guided Exploration of an Empirical Ribozyme Fitness Landscape

Okinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyFitness landscape of a biomolecule is a representation of its activity as a function of its sequence. Properties of a fitness landscape determine how evolution proceeds. Therefore, the distribution of functional variants and more importantly, the connectivity of these variants within the sequence space are important scientific questions. Exploration of these spaces, however, is impeded by the combinatorial explosion of the sequence space. High-throughput experimental methods have recently reduced this impediment but only modestly. Better computational methods are needed to fully utilize the rich information from these experimental data to better understand the properties of the fitness landscape. In this work, I seek to improve this exploration process by combining data from massively parallel experimental assay with smart library design using advanced computational techniques. I focus on an artificial RNA enzyme or ribozyme that can catalyze a ligation reaction between two RNA fragments. This chemistry is analogous to that of the modern RNA polymeraseenzymes, therefore, represents an important reaction in the origin of life. In the first chapter, I discuss the background to this work in the context of evolutionary theory of fitness landscape and its implications in biotechnology. In chapter 2, I explore the use of processes borrowed from the field of evolutionary computation to solve optimization problems using real experimental sequence-activity data. In chapter 3, I investigate the use of supervised machine learning models to extract information on epistatic interactions from the dataset collected during multiple rounds of directed evolution. I investigate and experimentally validate the extent to which a deep learning model can be used to guide a completely computational evolutionary algorithm towards distant regions of the fitness landscape. In the final chapter, I perform a comprehensive experimental assay of the combinatorial region explored by the deep learning-guided evolutionary algorithm. Using this dataset, I analyze higher-order epistasis and attempt to explain the increased predictability of the region sampled by the algorithm. Finally, I provide the first experimental evidence of a large RNA ‘neutral network’. Altogether, this work represents the most comprehensive experimental and computational study of the RNA ligase ribozyme fitness landscape to date, providing important insights into the evolutionary search space possibly explored during the earliest stages of life.doctoral thesi