Statistical Physics of Evolutionary Trajectories on Fitness Landscapes

Random walks on multidimensional nonlinear landscapes are of interest in many areas of science and engineering. In particular, properties of adaptive trajectories on fitness landscapes determine population fates and thus play a central role in evolutionary theory. The topography of fitness landscapes and its effect on evolutionary dynamics have been extensively studied in the literature. We will survey the current research knowledge in this field, focusing on a recently developed systematic approach to characterizing path lengths, mean first-passage times, and other statistics of the path ensemble. This approach, based on general techniques from statistical physics, is applicable to landscapes of arbitrary complexity and structure. It is especially well-suited to quantifying the diversity of stochastic trajectories and repeatability of evolutionary events. We demonstrate this methodology using a biophysical model of protein evolution that describes how proteins maintain stability while evolving new functions

Biophysical Fitness Landscapes for Transcription Factor Binding Sites

Evolutionary trajectories and phenotypic states available to cell populations are ultimately dictated by intermolecular interactions between DNA, RNA, proteins, and other molecular species. Here we study how evolution of gene regulation in a single-cell eukaryote S. cerevisiae is affected by the interactions between transcription factors (TFs) and their cognate genomic sites. Our study is informed by high-throughput in vitro measurements of TF-DNA binding interactions and by a comprehensive collection of genomic binding sites. Using an evolutionary model for monomorphic populations evolving on a fitness landscape, we infer fitness as a function of TF-DNA binding energy for a collection of 12 yeast TFs, and show that the shape of the predicted fitness functions is in broad agreement with a simple thermodynamic model of two-state TF-DNA binding. However, the effective temperature of the model is not always equal to the physical temperature, indicating selection pressures in addition to biophysical constraints caused by TF-DNA interactions. We find little statistical support for the fitness landscape in which each position in the binding site evolves independently, showing that epistasis is common in evolution of gene regulation. Finally, by correlating TF-DNA binding energies with biological properties of the sites or the genes they regulate, we are able to rule out several scenarios of site-specific selection, under which binding sites of the same TF would experience a spectrum of selection pressures depending on their position in the genome. These findings argue for the existence of universal fitness landscapes which shape evolution of all sites for a given TF, and whose properties are determined in part by the physics of protein-DNA interactions

Mathematical modeling accurately predicts the dynamics and scaling of nuclear growth in discrete cytoplasmic volumes

Scaling of nuclear size with cell size has been observed in many species and cell types. In this work we formulate a modeling framework based on the limiting component hypothesis. We derive a family of spatio-temporal mathematical models for nuclear size determination based on different transport and growth mechanisms. We analyse model properties and use in vitro experimental data to identify the most probable mechanism. This suggests that nuclear volume scales with cell volume and that a nucleus controls its import rate as it grows. We further test the model by comparing to data of early frog development, where rapid cell divisions set the relevant time scales

Additive Equivalence in Turbulent Drag Reduction by Flexible and Rodlike Polymers

We address the "Additive Equivalence" discovered by Virk and coworkers: drag reduction affected by flexible and rigid rodlike polymers added to turbulent wall-bounded flows is limited from above by a very similar Maximum Drag Reduction (MDR) asymptote. Considering the equations of motion of rodlike polymers in wall-bounded turbulent ensembles, we show that although the microscopic mechanism of attaining the MDR is very different, the macroscopic theory is isomorphic, rationalizing the interesting experimental observations.Comment: 8 pages, PRE, submitte

Effect of the Predecessor and the Nitrogen Rate on Productivity and Essential Oil Content of Coriander (Coriandrum sativum L.) in Southeast Bulgaria

Received: May 31st, 2022 ; Accepted: August 13th, 2022 ; Published: September 19th, 2022 ; Correspondence: [email protected] (Coriandrum sativum L.) is one of the most important essential oil crops on a global scale. Coriander productivity is determined by the genotype, the environmental factors, as well the agronomic practices. A field experiment was conducted in Southeast Bulgaria during three vegetation seasons (2015, 2016, and 2017). The present study aimed at analysing the influence of two crop predecessors (winter wheat and sunflower) and four nitrogen (N) levels (0, 40, 80, and 120 kg ha-1 ). Productivity elements, seed yield, and seed essential oil content of coriander (cv. Mesten drebnoploden) were under evaluation. The results obtained showed that winter wheat was a more suitable predecessor of coriander in comparison to sunflower. The highest results regarding the number of umbels per plant, the umbel’s diameter, the number of umbellets per umbel, the number of seeds per umbel, the seed weight per plant, the 1,000 seed mass, as well as the seed yield for the rate of 80 kg ha-1 of N were recorded. The highest essential oil content after applying 120 kg ha-1 of N was established. Increasing the N level from 0 to 120 kg ha-1 led to a positive and significant effect on essential oil yield. No significant differences between the N rates of 80 and 120 kg ha-1 were recorded. The received results contributed for the evaluatation of the optimum nitrogen level, as well as for the determination of a more suitable predecessor of coriander in order to obtain the highest yield of better quality in the region of Southeast Bulgaria

Stress‐response balance drives the evolution of a network module and its host genome

Stress response genes and their regulators form networks that underlie drug resistance. These networks often have an inherent tradeoff: their expression is costly in the absence of stress, but beneficial in stress. They can quickly emerge in the genomes of infectious microbes and cancer cells, protecting them from treatment. Yet, the evolution of stress resistance networks is not well understood. Here, we use a two‐component synthetic gene circuit integrated into the budding yeast genome to model experimentally the adaptation of a stress response module and its host genome in three different scenarios. In agreement with computational predictions, we find that: (i) intra‐module mutations target and eliminate the module if it confers only cost without any benefit to the cell; (ii) intra‐ and extra‐module mutations jointly activate the module if it is potentially beneficial and confers no cost; and (iii) a few specific mutations repeatedly fine‐tune the module's noisy response if it has excessive costs and/or insufficient benefits. Overall, these findings reveal how the timing and mechanisms of stress response network evolution depend on the environment

Differential item functioning for items in Berger's HIV Stigma Scale: an analysis of cohorts from the Indian, Swedish, and US contexts

PURPOSE: To examine whether items in Berger's HIV Stigma Scale function differently with persons of different age, gender, and cultural backgrounds. METHODS: Secondary data from cohorts, collected in South India (n = 250), Sweden (n = 193), and the US (n = 603) were reanalyzed to evaluate DIF within, between, and across these cohorts. All participants had answered the revised version of the HIV stigma scale consisting of 32 items forming the subscales Personalized stigma, Disclosure concerns, Concerns about public attitudes, and Negative self-image. Differential Item Functioning (DIF) for these items was assessed using hybrid ordinal regression-IRT technique. When DIF was detected, the cumulative impact of DIF on individual subscale scores was evaluated. RESULTS: DIF was detected for 9 items within, between, or across cohorts, but the DIF was negligible in general. Detected DIF between the Swedish and Indian cohorts had a cumulative salient impact on individual scores for the subscale Disclosure Concerns; Disclosure concerns were overestimated in the Swedish cohort and both over- and underestimated in the Indian cohort. CONCLUSIONS: The items in the 32-item version of the HIV stigma scale did not seem to be particularly prone to present DIF. The DIF between the Indian and Swedish cohort for items in the subscale Disclosure Concerns could, however, result in both type I and type II errors if scores should be compared between the Indian and Swedish cohort

Performance evaluation of automated urine microscopy as a rapid, non-invasive approach for the diagnosis of non-gonococcal urethritis.

OBJECTIVES: Gram-stained urethral smear (GSUS), the standard point-of-care test for non-gonococcal urethritis (NGU) is operator dependent and poorly specific. The performance of rapid automated urine flow cytometry (AUFC) of first void urine (FVU) white cell counts (UWCC) for predicting Mycoplasma genitalium and Chlamydia trachomatis urethral infections was assessed and its application to asymptomatic infection was evaluated. METHODS: Receiver operating characteristic curve analysis, determining FVU-UWCC threshold for predicting M. genitalium or C. trachomatis infection was performed on 208 'training' samples from symptomatic patients and subsequently validated using 228 additional FVUs obtained from prospective unselected patients. RESULTS: An optimal diagnostic threshold of >29 UWC/µL gave sensitivities and specificities for either infection of 81.5% (95% CI 65.1% to 91.6%) and 85.8% (79.5% to 90.4%), respectively, compared with 86.8% (71.1% to 95%) and 64.7% (56.9% to 71.7%), respectively, for GSUS, using the training set samples. FVU-UWCC demonstrated sensitivities and specificities of 69.2% (95% CI 48.1% to 84.9%) and 92% (87.2% to 95.2%), respectively, when using validation samples. In asymptomatic patients where GSUS was not used, AUFC would have enabled more infections to be detected compared with clinical considerations only (71.4% vs 28.6%; p=0.03). The correlation between UWCC and bacterial load was stronger for M. genitalium compared with C. trachomatis (τ=0.426, p≤0.001 vs τ=0.295, p=0.022, respectively). CONCLUSIONS: AUFC offers improved specificity over microscopy for predicting C. trachomatis or M. genitalium infection. Universal AUFC may enable non-invasive diagnosis of asymptomatic NGU at the PoC. The degree of urethral inflammation exhibits a stronger association with pathogen load for M. genitalium compared with C. trachomatis