Biology subjects

Frank, S. A.

Publications and source records attributed to Frank, S. A..

5 recordsLinked to original sources

bioRxiv2018

Evolutionary design of regulatory control. II. Robust error-correcting feedback increases genetic and phenotypic variability

As systems become more robust against perturbations, they can compensate for greater sloppiness in the performance of their components. That robust compensation reduces the force of natural selection on the systems components, leading to component decay. The paradoxical coupling of robustness and decay predicts that robust systems evolve cheaper, lower performing components, which accumulate greater mutational genetic variability and which have greater phenotypic stochasticity in trait expression. Previous work noted the paradox of robustness. However, no general theory for the evolutionary dynamics of system robustness and component decay has been developed. This article takes a first step by linking engineering control theory with the genetic theory of evolutionary dynamics. Control theory emphasizes error-correcting feedback as the single greatest principle in robust system design. Linking control theory to evolution leads to a theory for the evolutionary dynamics of error-correcting feedback, a unifying approach for the evolutionary analysis of robust systems. In this article, I study how, in theory, increasingly robust systems accumulate more genetic variability and greater stochasticity of expression in their components. The theory predicts different levels of variability between different regulatory control architectures and different levels of variability between different components within a particular regulatory control system. Those predictions provide a way to understand the accumulating data on genetic variability and single-cell stochasticity of gene expression. I also show that increasing robustness reduces the frequency of system failures associated with disease and, simultaneously, causes a strong increase in the heritability of disease. Thus, robust error correction in biological regulatory control may partly explain the puzzlingly high heritability of disease and, more generally, the surprisingly high heritability of fitness.

systems biology↗

bioRxiv2018

Measurement invariance explains the universal law of generalization for psychological perception

The universal law of generalization describes how animals discriminate between alternative sensory stimuli. On an appropriate perceptual scale, the probability that an organism perceives two stimuli as similar typically declines exponentially with the difference on the perceptual scale. Exceptions often follow a Gaussian probability pattern rather than an exponential pattern. Previous explanations have been based on underlying theoretical frameworks such as information theory, Kolmogorov complexity, or empirical multidimensional scaling. This article shows that the few inevitable invariances that must apply to any reasonable perceptual scale provide a sufficient explanation for the universal exponential law of generalization. In particular, reasonable measurement scales of perception must be invariant to shift by a constant value, which by itself leads to the exponential form. Similarly, reasonable measurement scales of perception must be invariant to multiplication, or stretch, by a constant value, which leads to the conservation of the slope of discrimination with perceptual difference. In some cases, an additional assumption about exchangeability or rotation of underlying perceptual dimensions leads to a Gaussian pattern of discrimination, which can be understood as a special case of the more general exponential form. The three measurement invariances of shift, stretch, and rotation provide a sufficient explanation for the universally observed patterns of perceptual generalization. All of the additional assumptions and language associated with information, complexity, and empirical scaling are superfluous with regard to the broad patterns of perception.

animal behavior and cognition↗

bioRxiv2018

Homeostasis, environmental tracking and phenotypic plasticity. I. A robust control theory approach to evolutionary design tradeoffs

The evolutionary design of regulatory control balances various tradeoffs in performance. Fast reaction to environmental change tends to favor plastic responsiveness at the expense of greater sensitivity to perturbations that degrade homeostatic control. Greater homeostatic stability against unpredictable disturbances tends to reduce performance in tracking environmental change. This article applies the classic principles of engineering control theory to the evolutionary design of regulatory systems. The engineering theory clarifies the conceptual aspects of evolutionary tradeoffs and provides analytic methods for developing specific predictions. On the conceptual side, this article clarifies the meanings of integral control, feedback, and design, concepts that have been discussed in a confusing way within the biological literature. On the analytic side, this article presents extensive methods and examples to study error-correcting feedback, which is perhaps the single greatest principle of design in both human-engineered and naturally designed systems. The broad framework and associated software code provide a comprehensive how-to guide for making models that focus on functional aspects of regulatory control and for making comparative predictions about regulatory design in response to various kinds of environmental challenge. The second article in this series analyzes how alternative regulatory designs influence the relative levels of genetic variability, stochasticity of trait expression, and heritability of disease.

evolutionary biology↗

bioRxiv2017

Receptor Uptake Arrays For Vitamin B12, Siderophores And Glycans Shape Bacterial Communities

Molecular variants of vitamin B12, siderophores and glycans occur. To take up variant forms, bacteria may express an array of receptors. The gut microbe Bacteroides thetaiotaomicron has three different receptors to take up variants of vitamin B12 and 88 receptors to take up various glycans. The design of receptor arrays reflects key processes that shape cellular evolution. Competition may focus each species on a subset of the available nutrient diversity. Some gut bacteria can take up only a narrow range of carbohydrates, whereas species such as B. thetaiotaomicron can digest many different complex glycans. Comparison of different nutrients, habitats, and genomes provide opportunity to test hypotheses about the breadth of receptor arrays. Another important process concerns fluctuations in nutrient availability. Such fluctuations enhance the value of cellular sensors, which gain information about environmental availability and adjust receptor deployment. Bacteria often adjust receptor expression in response to fluctuations of particular carbohydrate food sources. Some species may adjust expression of uptake receptors for specific siderophores. How do cells use sensor information to control the response to fluctuations? That question about regulatory wiring relates to problems that arise in control theory and artificial intelligence. Control theory clarifies how to analyze environmental fluctuations in relation to the design of sensors and response systems. Recent advances in deep learning studies of artificial intelligence focus on the architecture of regulatory wiring and the ways in which complex control networks represent and classify environmental states. I emphasize the similar design problems that arise in cellular evolution, control theory, and artificial intelligence. I connect those broad conceptual aspects to many testable hypotheses for bacterial uptake of vitamin B12, siderophores and glycans.

microbiology↗

bioRxiv2016

Universal expressions of population change by the Price equation: natural selection, information, and maximum entropy production

The Price equation shows the unity between the fundamental expressions of change in biology, in information and entropy descriptions of populations, and in aspects of thermodynamics. The Price equation partitions the change in the average value of a metric between two populations. A population may be composed of organisms or particles or any members of a set to which we can assign probabilities. A metric may be biological fitness or physical energy or the output of an arbitrarily complicated function that assigns quantitative values to members of the population. The first part of the Price equation describes how directly applied forces change the probabilities assigned to members of the population when holding constant the metrical values of the members--a fixed metrical frame of reference. The second part describes how the metrical values change, altering the metrical frame of reference. In canonical examples, the direct forces balance the changing metrical frame of reference, leaving the average or total metrical values unchanged. In biology, relative reproductive success (fitness) remains invariant as a simple consequence of the conservation of total probability. In physics, systems often conserve total energy. Nonconservative metrics can be described by starting with conserved metrics, and then studying how coordinate transformations between conserved and nonconserved metrics alter the geometry of the dynamics and the aggregate values of populations. From this abstract perspective, key results from different subjects appear more simply as universal geometric principles for the dynamics of populations subject to the constraints of particular conserved quantitiesa.

evolutionary biology↗