Maximum mutational robustness in genotype-phenotype maps follows a self-similar blancmange-like curve
Abstract:
Phenotype robustness, defined as the average mutational robustness of all the genotypes that map to a given phenotype, plays a key role in facilitating neutral exploration of novel phenotypic variation by an evolving population. By applying results from coding theory, we prove that the maximum phenotype robustness occurs when genotypes are organized as bricklayer's graphs, so-called because they resemble the way in which a bricklayer would fill in a Hamming graph. The value of the maximal robustness is given by a fractal continuous everywhere but differentiable nowhere sums-of-digits function from number theory. Interestingly, genotype-phenotype maps for RNA secondary structure and the hydrophobic-polar (HP) model for protein folding can exhibit phenotype robustness that exactly attains this upper bound. By exploiting properties of the sums-of-digits function, we prove a lower bound on the deviation of the maximum robustness of phenotypes with multiple neutral components from the bricklayer's graph bound, and show that RNA secondary structure phenotypes obey this bound. Finally, we show how robustness changes when phenotypes are coarse-grained and derive a formula and associated bounds for the transition probabilities between such phenotypes.Designing the self-assembly of arbitrary shapes using minimal complexity building blocks
Abstract:
The design space for self-assembled multicomponent objects ranges from a solution in which every building block is unique to one with the minimum number of distinct building blocks that unambiguously define the target structure. We develop a pipeline to explore the design spaces for a set of structures of various sizes and complexities. To understand the implications of the different solutions, we analyze their assembly dynamics using patchy particle simulations and study the influence of the number of distinct building blocks, and the angular and spatial tolerances on their interactions, on the kinetics and yield of the target assembly. We show that the resource-saving solution with a minimum number of distinct blocks can often assemble just as well (or faster) than designs where each building block is unique. We further use our methods to design multifarious structures, where building blocks are shared between different target structures. Finally, we use coarse-grained DNA simulations to investigate the realization of multicomponent shapes using DNA nanostructures as building blocks.Robustness and stability of spin-glass ground states to perturbed interactions
Abstract:
Across many problems in science and engineering, it is important to consider how much the output of a given system changes due to perturbations of the input. Here, we investigate the glassy phase of ± J spin glasses at zero temperature by calculating the robustness of the ground states to flips in the sign of single interactions. For random graphs and the Sherrington-Kirkpatrick model, we find relatively large sets of bond configurations that generate the same ground state. These sets can themselves be analyzed as subgraphs of the interaction domain, and we compute many of their topological properties. In particular, we find that the robustness, equivalent to the average degree, of these subgraphs is much higher than one would expect from a random model. Most notably, it scales in the same logarithmic way with the size of the subgraph as has been found in genotype-phenotype maps for RNA secondary structure folding, protein quaternary structure, gene regulatory networks, as well as for models for genetic programming. The similarity between these disparate systems suggests that this scaling may have a more universal origin.
Maximum Mutational Robustness in Genotype-Phenotype Maps Follows a Self-similar Blancmange-like Curve
Predicting phenotype transition probabilities via conditional algorithmic probability approximations
Abstract:
Unravelling the structure of genotype–phenotype (GP) maps is an important problem in biology. Recently, arguments inspired by algorithmic information theory (AIT) and Kolmogorov complexity have been invoked to uncover simplicity bias in GP maps, an exponentially decaying upper bound in phenotype probability with the increasing phenotype descriptional complexity. This means that phenotypes with many genotypes assigned via the GP map must be simple, while complex phenotypes must have few genotypes assigned. Here, we use similar arguments to bound the probability P(x → y) that phenotype x, upon random genetic mutation, transitions to phenotype y. The bound is P(x→y)≲2−aK~(y|x)−b , where K~(y|x) is the estimated conditional complexity of y given x, quantifying how much extra information is required to make y given access to x. This upper bound is related to the conditional form of algorithmic probability from AIT. We demonstrate the practical applicability of our derived bound by predicting phenotype transition probabilities (and other related quantities) in simulations of RNA and protein secondary structures. Our work contributes to a general mathematical understanding of GP maps and may facilitate the prediction of transition probabilities directly from examining phenotype themselves, without utilizing detailed knowledge of the GP map.