Geometry of fitness landscapes: peaks, shapes and universal positive epistasis.

Darwinian evolution is driven by random mutations, genetic recombination (gene shuffling) and selection that favors genotypes with high fitness. For systems where each genotype can be represented as a bitstring of length L, an overview of possible evolutionary trajectories is provided by the L-cube graph with nodes labeled by genotypes and edges directed toward the genotype with higher fitness. Peaks (sinks in the graphs) are important since a population can get stranded at a suboptimal peak.

Rank orders and signed interactions in evolutionary biology.

Rank orders have been studied in evolutionary biology for almost a hundred years. Constraints on the order in which mutations accumulate are known from cancer drug treatment, and order constraints for species invasions are important in ecology. However, current theory on rank orders in biology is somewhat fragmented.

An uncertainty law for microbial evolution.

Medical practice would benefit from a thorough understanding of constraints and uncertainty in microbial evolution. Higher order epistasis refers to unexpected effects of multiple mutations even if both single mutations and pairwise effects have been accounted for. Recent studies show that higher order epistasis is abundant in nature, for bacteria as well as higher organisms.

Recombination and peak jumping.

We show that genetic recombination can be a powerful mechanism for escaping suboptimal peaks. Recent studies of empirical fitness landscapes reveal complex gene interactions and multiple peaks. However, classical work on recombination largely ignores the effect of complex gene interactions.

Inferring genetic interactions from comparative fitness data.

Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations.

Epistasis and Entropy.

Epistasis is a key concept in the theory of adaptation. Indicators of epistasis are of interest for large systems where systematic fitness measurements may not be possible. Some recent approaches depend on information theory.

Rational design of antibiotic treatment plans: a treatment strategy for managing evolution and reversing resistance.

The development of reliable methods for restoring susceptibility after antibiotic resistance arises has proven elusive. A greater understanding of the relationship between antibiotic administration and the evolution of resistance is key to overcoming this challenge. Here we present a data-driven mathematical approach for developing antibiotic treatment plans that can reverse the evolution of antibiotic resistance determinants.

Subcutaneous and segmental fat loss with and without supportive supplements in conjunction with a low-calorie high protein diet in healthy women.

Background: Weight loss benefits of multi-ingredient supplements in conjunction with a low-calorie, high-protein diet in young women are unknown. Therefore, the purpose of this study was to investigate the effects of a three-week low-calorie diet with and without supplementation on body composition.

Methods: Thirty-seven recreationally-trained women (n = 37; age = 27.

Caloric expenditure of aerobic, resistance, or combined high-intensity interval training using a hydraulic resistance system in healthy men.

Although exercise regimens vary in content and duration, few studies have compared the caloric expenditure of multiple exercise modalities with the same duration. The purpose of this study was to compare the energy expenditure of single sessions of resistance, aerobic, and combined exercise with the same duration. Nine recreationally active men (age: 25 ± 7 years; height: 181.

The changing geometry of a fitness landscape along an adaptive walk.

It has recently been noted that the relative prevalence of the various kinds of epistasis varies along an adaptive walk. This has been explained as a result of mean regression in NK model fitness landscapes. Here we show that this phenomenon occurs quite generally in fitness landscapes.

Designing antibiotic cycling strategies by determining and understanding local adaptive landscapes.

The evolution of antibiotic resistance among bacteria threatens our continued ability to treat infectious diseases. The need for sustainable strategies to cure bacterial infections has never been greater. So far, all attempts to restore susceptibility after resistance has arisen have been unsuccessful, including restrictions on prescribing [1] and antibiotic cycling [2], [3].

The peaks and geometry of fitness landscapes.

Fitness landscapes are central in the theory of adaptation. Recent work compares global and local properties of fitness landscapes. It has been shown that multi-peaked fitness landscapes have a local property called reciprocal sign epistasis interactions.