The evolution of phenotypic correlations and “developmental memory”

Development introduces structured correlations among traits that may constrain or bias the distribution of phenotypes produced. Moreover, when suitable heritable variation exists, natural selection may alter such constraints and correlations, affecting the phenotypic variation available to subsequent selection. However, exactly how the distribution of phenotypes produced by complex developmental systems can be shaped by past selective environments is poorly understood. Here we investigate the evolution of a network of recurrent nonlinear ontogenetic interactions, such as a gene regulation network, in various selective scenarios. We find that evolved networks of this type can exhibit several phenomena that are familiar in cognitive learning systems. These include formation of a distributed associative memory that can “store” and “recall” multiple phenotypes that have been selected in the past, recreate complete adult phenotypic patterns accurately from partial or corrupted embryonic phenotypes, and “generalize” (by exploiting evolved developmental modules) to produce new combinations of phenotypic features. We show that these surprising behaviors follow from an equivalence between the action of natural selection on phenotypic correlations and associative learning, well-understood in the context of neural networks. This helps to explain how development facilitates the evolution of high-fitness phenotypes and how this ability changes over evolutionary time

Evolutionary dynamics of the most populated genotype on rugged fitness landscapes

We consider an asexual population evolving on rugged fitness landscapes which are defined on the multi-dimensional genotypic space and have many local optima. We track the most populated genotype as it changes when the population jumps from a fitness peak to a better one during the process of adaptation. This is done using the dynamics of the shell model which is a simplified version of the quasispecies model for infinite populations and standard Wright-Fisher dynamics for large finite populations. We show that the population fraction of a genotype obtained within the quasispecies model and the shell model match for fit genotypes and at short times, but the dynamics of the two models are identical for questions related to the most populated genotype. We calculate exactly several properties of the jumps in infinite populations some of which were obtained numerically in previous works. We also present our preliminary simulation results for finite populations. In particular, we measure the jump distribution in time and find that it decays as $t^{-2}$ as in the quasispecies problem.Comment: Minor changes. To appear in Phys Rev

Records and sequences of records from random variables with a linear trend

We consider records and sequences of records drawn from discrete time series of the form $X_{n}=Y_{n}+cn$, where the $Y_{n}$ are independent and identically distributed random variables and $c$ is a constant drift. For very small and very large drift velocities, we investigate the asymptotic behavior of the probability $p_n(c)$ of a record occurring in the $n$th step and the probability $P_N(c)$ that all $N$ entries are records, i.e. that $X_1 < X_2 < ... < X_N$. Our work is motivated by the analysis of temperature time series in climatology, and by the study of mutational pathways in evolutionary biology.Comment: 21 pages, 7 figure

genenames.org: the HGNC resources in 2011

The HUGO Gene Nomenclature Committee (HGNC) aims to assign a unique gene symbol and name to every human gene. The HGNC database currently contains almost 30 000 approved gene symbols, over 19 000 of which represent protein-coding genes. The public website, www.genenames.org, displays all approved nomenclature within Symbol Reports that contain data curated by HGNC editors and links to related genomic, phenotypic and proteomic information. Here we describe improvements to our resources, including a new Quick Gene Search, a new List Search, an integrated HGNC BioMart and a new Statistics and Downloads facility

Nonlinear acousto-electric transport in a two-dimensional electron system

We study both theoretically and experimentally the nonlinear interaction between an intense surface acoustic wave and a two-dimensional electron plasma in semiconductor-piezocrystal hybrid structures. The experiments on hybrid systems exhibit strongly nonlinear acousto-electric effects. The plasma turns into moving electron stripes, the acousto-electric current reaches its maximum, and the sound absorption strongly decreases. To describe the nonlinear phenomena, we develop a coupled-amplitude method for a two-dimensional system in the strongly nonlinear regime of interaction. At low electron densities the absorption coefficient decreases with increasing sound intensity, whereas at high electron density the absorption coefficient is not a monotonous function of the sound intensity. High-harmonic generation coefficients as a function of the sound intensity have a nontrivial behavior. Theory and experiment are found to be in a good agreement.Comment: 27 pages, 6 figure

Development and validation of a novel non-contact monitor of nocturnal respiration for identifying sleep-disordered breathing in patients with heart failure

© 2016 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. Aims: At least 50% of patients with heart failure (HF) may have sleep-disordered breathing (SDB). Overnight in-hospital polysomnography (PSG) is considered the gold standard for diagnosis, but a lack of access to such testing contributes to under-diagnosis of SDB. Therefore, there is a need for simple and reliable validated methods to aid diagnosis in patients with HF. The aim of this study was to investigate the accuracy of a non-contact type IV screening device, SleepMinderTM (SM), compared with in-hospital PSG for detecting SDB in patients with HF. Methods and results: The study included 75 adult patients with systolic HF and suspected SDB who underwent simultaneous PSG and SM recordings. An algorithm was developed from the SM signals, using digital signal processing and pattern recognition techniques to calculate the SM apnoea-hypopnoea index (AHI). This was then compared with expert-scored PSGAHI. The SM algorithm had 70% sensitivity and 89% specificity for identifying patients with clinically significant SDB (AHI ≥ 15/h). At this threshold, it had a positive likelihood ratio of 6.3 and a negative likelihood ratio of 0.16. The overall accuracy of the SMAHI algorithm was 85.8% as shown by the area under a receiver operator characteristic curve. The mean AHI with SM was 3.8/h (95% confidence interval 0.5–7.1) lower than that with PSG. Conclusions: The accuracy of the non-contact type IV screening device SM is good for clinically significant SDB in patients with systolic HF and could be considered as a simple first step in the diagnostic pathway

All-cause admissions following a first-ever exacerbation-related hospitalization in COPD

Background Hospital admissions are important contributors to the overall burden of chronic obstructive pulmonary disease (COPD). Understanding the patterns and causes of hospital admissions will help to identify targets for preventive interventions. This study aimed to determine the 5-year all-cause hospital admission trajectories of patients with COPD following their first ever exacerbation-related hospitalisation. Methods Patients with COPD were identified from the Danish national registries. Patients experiencing their first ever exacerbation-related hospitalisation, defined as the index event, between 2000 and 2014 were included. All-cause hospital admissions were examined during a subsequent 5-year follow-up period, and categorised using the International Classification of Diseases, 10th revision. Results In total, 82 964 patients with COPD were included. The mean±sd age was 72±10 years and 48% were male. Comorbidities were present in 58%, and 65% of the patients collected inhalation medication ≤6 months prior to the index event. In total, 337 066 all-cause hospital admissions were identified, resulting in a 5-year admission rate of 82%. Most admissions were due to nonrespiratory causes (59%), amongst which cardiac events were most common (19%). Conclusion Hospital admissions following a first exacerbation-related hospitalisation are common; nonrespiratory events constitute the majority of admissions. Besides the respiratory causes, treatment targeting the nonrespiratory causes of hospital admission should be considered to effectively decrease the burden of hospitalisation in COPD

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure