Information-geometric optimization with natural selection

Evolutionary algorithms, inspired by natural evolution, aim to optimize difficult objective functions without computing derivatives. Here we detail the relationship between population genetics and evolutionary optimization and formulate a new evolutionary algorithm. Optimization of a continuous objective function is analogous to searching for high fitness phenotypes on a fitness landscape. We summarize how natural selection moves a population along the non-euclidean gradient that is induced by the population on the fitness landscape (the natural gradient). Under normal approximations common in quantitative genetics, we show how selection is related to Newton's method in optimization. We find that intermediate selection is most informative of the fitness landscape. We describe the generation of new phenotypes and introduce an operator that recombines the whole population to generate variants that preserve normal statistics. Finally, we introduce a proof-of-principle algorithm that combines natural selection, our recombination operator, and an adaptive method to increase selection. Our algorithm is similar to covariance matrix adaptation and natural evolutionary strategies in optimization, and has similar performance. The algorithm is extremely simple in implementation with no matrix inversion or factorization, does not require storing a covariance matrix, and may form the basis of more general model-based optimization algorithms with natural gradient updates.Comment: changed titl

Speeding up evolutionary search by small fitness fluctuations

We consider a fixed size population that undergoes an evolutionary adaptation in the weak mutuation rate limit, which we model as a biased Langevin process in the genotype space. We show analytically and numerically that, if the fitness landscape has a small highly epistatic (rough) and time-varying component, then the population genotype exhibits a high effective diffusion in the genotype space and is able to escape local fitness minima with a large probability. We argue that our principal finding that even very small time-dependent fluctuations of fitness can substantially speed up evolution is valid for a wide class of models.Comment: 12 pages, 5 figure

Fierce selection and interference in B-cell repertoire response to chronic HIV-1

During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host's adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic evolution that shape the immune response are still unknown. Traditional population genetics methods fail to distinguish chronic immune response from healthy repertoire evolution. Here, we infer the evolutionary modes of B-cell repertoires and identify complex dynamics with a constant production of better B-cell receptor mutants that compete, maintaining large clonal diversity and potentially slowing down adaptation. A substantial fraction of mutations that rise to high frequencies in pathogen engaging CDRs of B-cell receptors (BCRs) are beneficial, in contrast to many such changes in structurally relevant frameworks that are deleterious and circulate by hitchhiking. We identify a pattern where BCRs in patients who experience larger viral expansions undergo stronger selection with a rapid turnover of beneficial mutations due to clonal interference in their CDR3 regions. Using population genetics modeling, we show that the extinction of these beneficial mutations can be attributed to the rise of competing beneficial alleles and clonal interference. The picture is of a dynamic repertoire, where better clones may be outcompeted by new mutants before they fix

Totally Asymmetric Exclusion Process with Hierarchical Long-Range Connections

A non-equilibrium particle transport model, the totally asymmetric exclusion process, is studied on a one-dimensional lattice with a hierarchy of fixed long-range connections. This model breaks the particle-hole symmetry observed on an ordinary one-dimensional lattice and results in a surprisingly simple phase diagram, without a maximum-current phase. Numerical simulations of the model with open boundary conditions reveal a number of dynamic features and suggest possible applications.Comment: 10 pages, revtex4, reorganized, with some new analytical results. For related articles, see http://www.physics.emory.edu/faculty/boettcher

Learning the shape of protein micro-environments with a holographic convolutional neural network

Proteins play a central role in biology from immune recognition to brain activity. While major advances in machine learning have improved our ability to predict protein structure from sequence, determining protein function from structure remains a major challenge. Here, we introduce Holographic Convolutional Neural Network (H-CNN) for proteins, which is a physically motivated machine learning approach to model amino acid preferences in protein structures. H-CNN reflects physical interactions in a protein structure and recapitulates the functional information stored in evolutionary data. H-CNN accurately predicts the impact of mutations on protein function, including stability and binding of protein complexes. Our interpretable computational model for protein structure-function maps could guide design of novel proteins with desired function

Clonal interference and Muller's ratchet in spatial habitats

Competition between independently arising beneficial mutations is enhanced in spatial populations due to the linear rather than exponential growth of clones. Recent theoretical studies have pointed out that the resulting fitness dynamics is analogous to a surface growth process, where new layers nucleate and spread stochastically, leading to the build up of scale-invariant roughness. This scenario differs qualitatively from the standard view of adaptation in that the speed of adaptation becomes independent of population size while the fitness variance does not. Here we exploit recent progress in the understanding of surface growth processes to obtain precise predictions for the universal, non-Gaussian shape of the fitness distribution for one-dimensional habitats, which are verified by simulations. When the mutations are deleterious rather than beneficial the problem becomes a spatial version of Muller's ratchet. In contrast to the case of well-mixed populations, the rate of fitness decline remains finite even in the limit of an infinite habitat, provided the ratio $U_d/s^2$ between the deleterious mutation rate and the square of the (negative) selection coefficient is sufficiently large. Using again an analogy to surface growth models we show that the transition between the stationary and the moving state of the ratchet is governed by directed percolation