Selective Constraints Research Articles

I2BODIPY as a new photoswitchable spin label for light-induced pulsed EPR dipolar spectroscopy exploiting magnetophotoselection.

Electron paramagnetic resonance (EPR) pulsed dipolar spectroscopy (PDS) using triplet states of organic molecules is a growing area of research due to the favourable properties that these transient states may afford over stable spin centers, such as switchability, increased signal intensity when the triplet is formed in a non-Boltzmann distribution and the triplet signal is used for detection, and high orientation selection, when the triplet signal is probed by microwave pulses. This arises due to the large spectral width at low fields, a result of the large zero field splitting, and limited bandwidth of microwave pulses used. Here we propose the triplet state of a substituted BODIPY moiety as a spin label in light induced PDS, coupled to a nitroxide, in a model peptide with a rigid structure. Orientation selection allows information on the relative position of the centres of the two labels to be obtained with respect to the nitroxide reference frame. Additionally, magnetophotoselection effects are employed to introduce optical selection and additional constraints for the determination of the relative orientation of the spin labels considering the reference frame of the triplet state.

Selection on synonymous codon usage in soybean (Glycine max) WRKY genes

The WRKY transcription factor gene family in soybean [Glycine max (L.) Merr.] (GmWRKY) is critical for the plant’s development and stress responses. This study examines the evolutionary dynamics of the GmWRKY gene family, focusing on its synonymous codon usage bias (CUB) in a comprehensive set of 179 coding sequences. CUB was analyzed using various indices, revealing a preference for A/T-ending codons and relatively low codon bias. Codon adaptation index (CAI) analysis suggested that these genes are optimized for efficient translation despite relatively low bias, reflecting a balance between codon diversity and translation efficiency. Neutrality and NC plots indicated that selective forces dominate over mutational forces in shaping codon usage, while selection signature analysis showed purifying selection being prevalent across the gene family. However, episodic positive selection was also detected in certain clades, highlighting potential adaptive diversification in response to environmental stress. Additionally, promoter binding site analysis uncovered correlations between codon usage and transcriptional regulation, indicating a context-dependent relationship between CUB and gene expression. Phylogenetic analysis identified 11 well-supported clades in the modern GmWRKY gene family and ancestral sequence reconstruction revealed more relaxed codon preferences and reduced selection constraints in modern GmWRKY genes, potentially linked to neofunctionalization and adaptation to environmental changes. These findings provide a framework for optimizing gene expression in transgenic soybean crops with resilience. Further functional validation of positively selected genes is recommended to elucidate their role in stress responses.

Binocular camera-based visual localization with optimized keypoint selection and multi-epipolar constraints

Binocular camera-based visual localization with optimized keypoint selection and multi-epipolar constraints

A Roadmap for Navigating Phenomenon-Based Research in Management

McNamara and Schleicher have identified four principal paths for contributing to the Journal of Management (JOM): theoretical insights, phenomenon-driven research, research methodologies, and review papers. This editorial focuses on phenomenon-based research, emphasizing its potential for enhancing management knowledge by offering a nuanced understanding of real-world phenomena. Unlike traditional approaches, phenomenon-based research prioritizes the complexity of phenomena over the immediate generation of theoretical contributions. Grounded in established theory, phenomenon-based research utilizes the phenomenon itself as the primary source of insight, facilitating the development of relevant organizational frameworks. We propose a multistep framework encompassing phenomenon selection, framing, data collection, and study constraints, highlighting criteria—Pertinence, Reach, Insightfulness, Magnification, and Expediency (PRIME)—to guide scholars in identifying meaningful phenomena. Additionally, we discuss constraints that may limit research, including cultural, logistical, ethical, academic, and resource-related challenges (CLEAR). By addressing these considerations, we encourage management scholars to explore diverse and impactful phenomena, ultimately aiming to position JOM as a leading platform for phenomenon-based research and its contributions to real-world organizational challenges. This editorial advocates for a balanced approach that values both theory-driven and phenomenon-driven research in advancing management scholarship.

Stress-Induced Constraint on Expression Noise of Essential Genes in E. coli.

Gene expression is an inherently noisy process that is constrained by natural selection. Yet the condition dependence of constraint on expression noise remains unclear. Here, we address this problem by studying constraint on expression noise of E. coli genes in eight diverse growth conditions. In particular, we use variation in expression noise as an analog for constraint, examining its relationships to expression level and to the number of regulatory inputs from transcription factors across and within conditions. We show that variation in expression noise is negatively associated with expression level, implicating constraint to minimize expression noise of highly expressed genes. However, this relationship is condition dependent, with the strongest constraint observed when E. coli are grown in the presence of glycerol or ciprofloxacin, which result in carbon or antibiotic stress, respectively. In contrast, we do not observe evidence of constraint on expression noise of highly regulated genes, suggesting that highly expressed and highly regulated genes represent distinct classes of genes. Indeed, we find that essential genes are often highly expressed but not highly regulated, with elevated expression noise in glycerol and ciprofloxacin conditions. Thus, our findings support the hypothesis that selective constraint on expression noise is condition dependent in E. coli, illustrating how it may play a critical role in ensuring expression stability of essential genes in unstable environments.

Energy‐efficient power allocation and antenna selection in full‐duplex multi‐cell distributed antenna systems

AbstractEnergy efficiency problem is investigated in distributed antenna systems (DAS), in which both users and base station (BS) antennas are full‐duplex (FD) capable. Multi‐cell and multi‐user scenario is considered. Users transmit power, BS antennas transmit power, and BS antenna selection are jointly optimized under single‐antenna power constraints, per‐user power constraints, and antenna selection constraints. Using the fractional programming, we convert the objective function equivalently from the fractional form to subtractive form. Then, the reformulated problem is decomposed into two subproblems for iterative optimization, the local optimal solution is obtained. Simulation results show the energy efficiency is significantly better than other reference algorithms and close to the optimal algorithm.

Purifying Selection Influences the Comparison of Heterozygosities between Populations.

Heterozygosity is a fundamental measure routinely used to compare between populations to infer the level of genetic variation and their relative effective population sizes. However, such comparison is highly influenced by the magnitude of selection pressure on the genomic regions used. Using over 2 million Single Nucleotide Variants (SNVs) from chimpanzee and mouse populations, this study shows that the heterozygosities estimated using neutrally evolving sites of large populations were two times higher than those of small populations. However, this difference was only ~1.6 times for the heterozygosities estimated using nonsynonymous sites. This suggests an excess in the nonsynonymous heterozygosities due to the segregation of deleterious variants in small populations. This excess in the nonsynonymous heterozygosities of the small populations was estimated to be 23-31%. Further analysis revealed that the magnitude of the excess is modulated by effective population size (Ne) and selection intensity (s). Using chimpanzee populations, this investigation found that the excess in nonsynonymous diversity in the small population was little (6%) when the difference between the Ne values of large and small populations was small (2.4 times). Conversely, this was high (23%) when the difference in Ne was large (5.9 times). Analysis using mouse populations showed that the excess in the nonsynonymous diversity of highly constrained genes of the small population was much higher (38%) than that observed for the genes under relaxed selective constraints (21%). Similar results were observed when the expression levels of genes were used as a proxy for selection intensity. These results emphasize the use of neutral regions, less constrained genes, or lowly expressed genes when comparing the heterozygosities between populations.

Selection on the vascular-remodeling BMPER gene is associated with altitudinal adaptation in an insular lizard

Abstract High altitude imposes several extreme constraints on life, such as low oxygen pressure and high levels of ultraviolet radiation, which require specialized adaptations. Many studies have focused on how endothermic vertebrates respond to these challenging environments, but there is still uncertainty on how ectotherms adapt to these conditions. Here, we used whole-genome sequencing of low-altitude (100–600 m) and high-altitude (3,550 m) populations of the wide-ranging Tenerife lizard Gallotia galloti to uncover signatures of selection for altitudinal adaptation. The studied populations show reduced differentiation, sharing similar patterns of genetic variation. Selective sweep mapping suggests that signatures of adaptation to high altitude are not widespread across the genome, clustering in a relatively small number of genomic regions. One of these regions contains BMPER, a gene involved with vascular remodeling, and that has been associated with hypoxia-induced angiogenic response. By genotyping samples across 2 altitudinal transects, we show that allele frequency changes at this locus are not gradual, but rather show a well-defined shift above ca. 1,900 m. Transcript and protein structure analyses on this gene suggest that putative selection likely acts on noncoding variation. These results underline how low oxygen pressure generates the most consistent selective constraint in high-altitude environments, to which vertebrates with vastly contrasting physiological profiles need to adapt in the context of ongoing climate change.

Recent Research on the Human Biology of Pastoralists.

Despite encroachment by agricultural systems and globalization, pastoral nomads maintain a robust presence in terms of numbers and subsistence activity. At the same time, increasing concern about climate change has promoted awareness that increased climatic fluctuation may push pastoral population past their capacity for resilience. The response of pastoralists to climate change has important implications for our evolutionary past and our increasingly problematic future. Yet, pastoralists have received less explicit attention than foragers as populations under consistent selective constraints including limited caloric intake, high levels of habitual activity, and high disease burdens. Additional factors include exposure to cold and high temperatures, as well as high altitude. Over the last 20 or so years, the use of new techniques for measuring energetics, including actigraphs and doubly labeled water have built on existing noninvasive sample collection for hormones, immune markers and genes to provide a more detailed picture of the human biology of pastoral populations. Here I consider recent work on pastoralists from Siberia and northern Europe, Africa, Asia, and South America. I survey what is known about maternal milk composition and infant health, childhood growth, lactase persistence, and adult energy expenditure and lactase persistence to build a picture of the pastoralist biological response to environmental conditions, including heat, cold, and high altitude. Where available I include information about population history because of its importance for selection. I end by outlining the impact of milk consumption and climate over the human life cycle and make suggestions for further research.

DUDS: Diversity-aware unbiased device selection for federated learning on Non-IID and unbalanced data

Federated Learning (FL) is a distributed machine learning approach that preserves privacy by allowing numerous devices to collaboratively train a global model without sharing raw data. However, the frequent exchange of model updates between numerous devices and the central server, and some model updates are similar and redundant, resulting in a waste of communication and computation. Selecting a subset of all devices for FL training can mitigate this issue. Nevertheless, most existing device selection methods are biased, while unbiased methods often perform unstable on Non-Independent Identically Distributed (Non-IID) and unbalanced data. To address this, we propose a stable Diversity-aware Unbiased Device Selection (DUDS) method for FL on Non-IID and unbalanced data. DUDS diversifies the participation probabilities for device sampling in each FL training round, mitigating the randomness of the individual device selection process. By using a leader-based cluster adjustment mechanism to meet unbiased selection constraints, DUDS achieves stable convergence and results close to the optimal, as if all devices participated. Extensive experiments demonstrate the effectiveness of DUDS on Non-IID and unbalanced data scenarios in FL.

Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection.

New genes (or young genes) are genetic novelties pivotal in mammalian evolution. However, their phenotypic impacts and evolutionary patterns over time remain elusive in humans due to the technical and ethical complexities of functional studies. Integrating gene age dating with Mendelian disease phenotyping, our research shows a gradual rise in disease gene proportion as gene age increases. Logistic regression modeling indicates that this increase in older genes may be related to their longer sequence lengths and higher burdens of deleterious de novo germline variants (DNVs). We also find a steady integration of new genes with biomedical phenotypes into the human genome over macroevolutionary timescales (~0.07% per million years). Despite this stable pace, we observe distinct patterns in phenotypic enrichment, pleiotropy, and selective pressures across gene ages. Notably, young genes show significant enrichment in diseases related to the male reproductive system, indicating strong sexual selection. Young genes also exhibit disease-related functions in tissues and systems potentially linked to human phenotypic innovations, such as increased brain size, musculoskeletal phenotypes, and color vision. We further reveal a logistic growth pattern of pleiotropy over evolutionary time, indicating a diminishing marginal growth of new functions for older genes due to intensifying selective constraints over time. We propose a pleiotropy-barrier model that delineates higher potentials for phenotypic innovation in young genes compared to older genes, a process that is subject to natural selection. Our study demonstrates that evolutionarily new genes are critical in influencing human reproductive evolution and adaptive phenotypic innovations driven by sexual and natural selection, with low pleiotropy as a selective advantage.

Selection on genome-wide gene expression plasticity of rice in wet and dry field environments.

Gene expression can be highly plastic in response to environmental variation. However, we know little about how expression plasticity is shaped by natural selection and evolves in wild and domesticated species. We used genotypic selection analysis to characterize selection on drought-induced plasticity of over 7,500 leaf transcripts of 118 rice accessions (genotypes) from different environmental conditions grown in a field experiment. Gene expression plasticity was neutral for most gradually plastic transcripts, but transcripts with discrete patterns of expression showed stronger selection on expression plasticity. Whether plasticity was adaptive and co-gradient or maladaptive and counter-gradient varied among varietal groups. No transcripts that experienced selection for plasticity across environments showed selection against plasticity within environments, indicating a lack of evidence for costs of adaptive plasticity that may constrain its evolution. Selection on expression plasticity was influenced by degree of plasticity, transcript length and gene body methylation. We observed positive selection on plasticity of co-expression modules containing transcripts involved in photosynthesis, translation and responsiveness to abiotic stress. Taken together, these results indicate that patterns of selection on expression plasticity were context-dependent and likely associated with environmental conditions of varietal groups, but that the evolution of adaptive plasticity would likely not be constrained by opposing patterns of selection on plasticity within compared to across environments. These results offer a genome-wide view of patterns of selection and ecological constraints on gene expression plasticity and provide insights into the interplay between plastic and evolutionary responses to drought at the molecular level.

Nested Randomized Controlled Trials in Large Databases: An Opportunity for Inflammatory Bowel Disease?

Although randomized controlled trials (RCTs) are the gold standard for investigating the efficacy and safety of interventions, they present major operational challenges due to their complexity, time-consuming nature, and high costs. To address some of these difficulties, RCTs nested in cohorts (RCTsNC) have been developed to enable patient enrolment and randomization from existing databases. RCTsNC is an emerging trial design, which has been successfully utilized across several medical disciplines but not inflammatory bowel disease (IBD). This narrative review outlines the principles of RCTsNC and discusses the numerous advantages it affords for IBD, including harnessing longer-term longitudinal data for safety and efficacy assessment, and enhanced recruitment and follow up processes. Leveraging pre-existing cohorts and their organizational structures improves patient acceptance and is more economical compared to traditional randomized trials. Observational data for IBD, derived from research (cohort and case-control studies) and non-research sources (electronic health records and registries), provides access to comprehensive records for a large number of IBD patients. It permits researchers to address knowledge gaps in IBD where traditional RCTs have had a limited role, such as specific sub-populations typically excluded from pivotal trials, or assessing the effect of environmental exposures on disease course. This review also details caveats of this study design that include the risk of selection bias and constraints related to comparisons with placebo. In conclusion, RCTsNC offers a promising opportunity IBD research given the challenges of the current IBD RCT landscape.

A homogeneous multi-vehicle cooperative group decision-making method in complicated mixed traffic scenarios

Connected and Automated Vehicles (CAVs) are expected to reshape the transportation system, and cooperative group intelligence of CAVs has great potential for improving transportation efficiency and safety. One challenge for CAV group driving is the decision-making under scenarios mixed with CAV and human-driven vehicles (HDV). Current studies mainly use methods based on single physical rules such as platoon driving or formation switch control, failing to reach a balanced and homogeneous state of optimal efficiency and risk in mixed traffic environments. In addition, most studies focus only on one specific type of scene, lacking the scene adaptability to various surrounding conditions. This paper proposes a homogeneous multi-vehicle cooperative group decision-making method targeting mixed traffic scenarios. A bi-level framework composed of behavior-level and trajectory-level decision-making is established to achieve balanced optimal cooperation. A region-driven behavioral decision mechanism is designed to decompose vehicle actions into a unified form of sequential target regions. Solutions are derived based on Cooperative Driving Safety Field, a risk assessment module inspired by field energy theory. The trajectory-level decision module takes the target regions as input and generates the control quantities of the CAVs through target point selection, conflict reconciliation, and dynamic constraint consideration. Experimental results on 19 various scenarios and continuous traffic flow scenes indicate that the proposed method significantly increases passing efficiency, reduces driving risk, and improves scene adaptability. In addition, experiments on multiple kinds of scenarios including intersections, ramps, bottlenecks, etc. prove that our method can adapt to various road topology structures. Feasibility is also verified through scaled physical platform validations and real-vehicle road tests.

A conserved opal termination codon optimizes a temperature-dependent tradeoff between protein production and processing in alphaviruses.

Alphaviruses are enveloped, single-stranded, positive-sense RNA viruses that often require transmission between arthropod and vertebrate hosts for their sustained propagation. Most alphaviruses encode an opal (UGA) termination codon in nonstructural protein 3 (nsP3) upstream of the viral polymerase, nsP4. The selective constraints underlying the conservation of the opal codon are poorly understood. Using primate and mosquito cells, we explored the role and selective pressure on the nsP3 opal codon through extensive mutational analysis in the prototype alphavirus, Sindbis virus (SINV). We found that the opal codon is highly favored over all other codons in primate cells under native 37°C growth conditions. However, this preference is diminished in mosquito and primate cells grown at a lower temperature. Thus, the primary determinant driving the selection of the opal stop codon is not host genetics but the passaging temperature. We show that the opal codon is preferred over amber and ochre termination codons because it results in the highest translational readthrough and polymerase production. However, substituting the opal codon with sense codons leads to excessive full-length polyprotein (P1234) production, which disrupts optimal nsP polyprotein processing, delays the switch from minus-strand to positive-strand RNA production, and significantly reduces SINV fitness at 37°C; this fitness defect is relieved at lower temperatures. A naturally occurring suppressor mutation unexpectedly compensates for a delayed transition from minus to genomic RNA production by also delaying the subsequent transition between genomic and sub-genomic RNA production. Our study reveals that the opal stop codon is the best solution for alphavirus replication at 37°C, producing enough nsP4 protein to maximize replication without disrupting nsP processing and RNA replication transitions needed for optimal fitness. Our study uncovers the intricate strategy dual-host alphaviruses use at a single codon to optimize fitness.

Mitochondrial DNA Genomes Reveal Relaxed Purifying Selection During Human Population Expansion after the Last Glacial Maximum.

Modern humans have experienced explosive population growth in the past thousand years. We hypothesized that recent human populations have inhabited environments with relaxation of selective constraints, possibly due to the more abundant food supply after the Last Glacial Maximum. The ratio of nonsynonymous to synonymous mutations (N/S ratio) is a useful and common statistic for measuring selective constraints. In this study, we reconstructed a high-resolution phylogenetic tree using a total of 26,419 East Eurasian mitochondrial DNA genomes, which were further classified into expansion and nonexpansion groups on the basis of the frequencies of their founder lineages. We observed a much higher N/S ratio in the expansion group, especially for nonsynonymous mutations with moderately deleterious effects, indicating a weaker effect of purifying selection in the expanded clades. However, this observation on N/S ratio was unlikely in computer simulations where all individuals were under the same selective constraints. Thus, we argue that the expanded populations were subjected to weaker selective constraints than the nonexpanded populations were. The mildly deleterious mutations were retained during population expansion, which could have a profound impact on present-day disease patterns.

Widespread natural selection on metabolite levels in humans.

Natural selection acts ubiquitously on complex human traits, predominantly constraining the occurrence of extreme phenotypes (stabilizing selection). These constraints propagate to DNA sequence variants associated with traits under selection. The genetic signatures of such evolutionary events can thus be detected via combining effect size estimates from genetic association studies and the corresponding allele frequencies. Although this approach has been successfully applied to high-level traits, the prevalence and mode of selection acting on molecular traits remain poorly understood. Here, we estimate the action of natural selection on genetic variants associated with metabolite levels, an important layer of molecular traits. By leveraging summary statistics of published genome-wide association studies with large sample sizes, we find strong evidence of stabilizing selection for 15 out of 97 plasma metabolites, with nonessential amino acids displaying especially strong selection signatures. Mendelian randomization analysis reveals that metabolites under stronger stabilizing selection display larger effects on a range of clinically relevant complex traits, suggesting that maintaining a disease-free profile may be an important source of selective constraints on the metabolome. Metabolites under strong stabilizing selection in humans are also more conserved in their concentrations among diverse mammalian species, suggesting shared selective forces across micro- and macroevolutionary timescales. Overall, this study demonstrates that variation in metabolite levels among humans is frequently shaped by natural selection and this may act through their causal impact on disease susceptibility.

Variable Craniofacial Shape and Development among Multiple Cave-Adapted Populations of Astyanax mexicanus.

Astyanax mexicanus is a freshwater fish species with blind cave morphs and sighted surface morphs. Like other troglodytic species, independently evolved cave-dwelling A. mexicanus populations share several stereotypic phenotypes, including the expansion of certain sensory systems, as well as the loss of eyes and pigmentation. Here, we assess the extent to which there is also parallelism in craniofacial development across cave populations. Since multiple forces may be acting upon variation in the A. mexicanus system, including phylogenetic history, selection, and developmental constraint, several outcomes are possible. For example, eye regression may have triggered a conserved series of compensatory developmental events, in which case we would expect to observe highly similar craniofacial phenotypes across cave populations. Selection for cave-specific foraging may also lead to the evolution of a conserved craniofacial phenotype, especially in regions of the head directly associated with feeding. Alternatively, in the absence of a common axis of selection or strong developmental constraints, craniofacial shape may evolve under neutral processes such as gene flow, drift, and bottlenecking, in which case patterns of variation should reflect the evolutionary history of A. mexicanus. Our results found that cave-adapted populations do share certain anatomical features; however, they generally did not support the hypothesis of a conserved craniofacial phenotype across caves, as nearly every pairwise comparison was statistically significant, with greater effect sizes noted between more distantly related cave populations with little gene flow. A similar pattern was observed for developmental trajectories. We also found that morphological disparity was lower among all three cave populations versus surface fish, suggesting eye loss is not associated with increased variation, which would be consistent with a release of developmental constraint. Instead, this pattern reflects the relatively low genetic diversity within cave populations. Finally, magnitudes of craniofacial integration were found to be similar among all groups, meaning that coordinated development among anatomical units is robust to eye loss in A. mexicanus. We conclude that, in contrast to many conserved phenotypes across cave populations, global craniofacial shape is more variable, and patterns of shape variation are more in line with population structure than developmental architecture or selection.

Testing the genomic overlap between intraspecific mating traits and interspecific mating barriers

Abstract Differences in interspecific mating traits, such as male sexual signals and female preferences, often evolve quickly as initial barriers to gene flow between nascent lineages, and they may also strengthen such barriers during secondary contact via reinforcement. However, it is an open question whether loci contributing to intraspecific variation in sexual traits are co-opted during the formation and strengthening of mating barriers between species. To test this, we used a population genomics approach in natural populations of Australian cricket sister species that overlap in a contact zone: Teleogryllus oceanicus and Teleogryllus commodus. First, we identified loci associated with intraspecific variation in T. oceanicus mating signals: advertisement song and cuticular hydrocarbon (CHC) pheromones. We then separately identified candidate interspecific barrier loci between the species. Genes showing elevated allelic divergence between species were enriched for neurological functions, indicating potential behavioral rewiring. Only two CHC-associated genes overlapped with these interspecific candidate barrier loci, and intraspecific CHC loci showed signatures of being under strong selective constraints between species. In contrast, 10 intraspecific song-associated genes showed high genetic differentiation between T. commodus and T. oceanicus, and 2 had signals of high genomic divergence. The overall lack of shared loci in intra vs. interspecific comparisons of mating trait and candidate barrier loci is consistent with limited co-option of the genetic architecture of interspecific mating signals during the establishment and maintenance of reproductive isolation.

A rotational/roto-translational constraint method for condensed matter.

Molecular rotations influence numerous condensed matter phenomena but are often difficult to isolate in molecular dynamics (MD) simulations. This work presents a rotational/roto-translational constraint algorithm designed for condensed matter simulations. The method is based on the velocity Verlet scheme, ensuring a direct constraint on velocity and simplifying implementation within material simulation software packages. We implemented the algorithm in a customized version of a CP2K package and validated its effectiveness through MD simulations of molecule and crystal. The results demonstrate successful selective constraint of rotational and roto-translational motions, enabling stable long-term simulations. This capability opens avenues for studying rotation-related phenomena (e.g., paddle-wheel mechanism in solid-state electrolytes) and constrained sampling.