Selective Advantage Research Articles

Long-term reliable wireless H2 gas sensor via repeatable thermal refreshing of palladium nanowire

The increasing significance of hydrogen (H2) gas as a clean energy source has prompted the development of high-performance H2 gas sensors. Palladium (Pd)-based sensors, with their advantages of selectivity, scalability, and cost-effectiveness, have shown promise in this regard. However, the long-term stability and reliability of Pd-based sensors remain a challenge. This study not only identifies the exact cause for performance degradation in palladium (Pd) nanowire H2 sensors, but also implements and optimizes a cost-effective recovery method. The results from density functional theory (DFT) calculations and material analysis confirm the presence of C = O bonds, indicating performance degradation due to carbon dioxide (CO2) accumulation on the Pd surface. Based on the molecular behavior calculation in high temperatures, we optimized the thermal treatment method of 200 °C for 10 minutes to remove the C = O contaminants, resulting in nearly 100% recovery of the sensor’s initial performance even after 2 months of contamination.

The Reindeer Circadian Clock Is Rhythmic and Temperature-compensated But Shows Evidence of Weak Coupling Between the Secondary and Core Molecular Clock Loops.

Circadian rhythms synchronize the internal physiology of animals allowing them to anticipate daily changes in their environment. Arctic habitats may diminish the selective advantages of circadian rhythmicity by relaxing daily rhythmic environmental constraints, presenting a valuable opportunity to study the evolution of circadian rhythms. In reindeer, circadian control of locomotor activity and melatonin release is weak or absent, and the molecular clockwork is reportedly non-functional. Here we present new evidence that the circadian clock in cultured reindeer fibroblasts is rhythmic and temperature-compensated. Compared with mouse fibroblasts, however, reindeer fibroblasts have a short free-running period, and temperature cycles have an atypical impact on clock gene regulation. In reindeer cells, Per2 and Bmal1 reporters show rapid responses to temperature cycles, with a disintegration of their normal antiphasic relationship. The antiphasic Per2-Bmal1 relationship re-emerges immediately after release from temperature cycles, but without complete temperature entrainment and with a marked decline in circadian amplitude. Experiments using Bmal1 promoter reporters with mutated RORE sites showed that a reindeer-like response to temperature cycles can be mimicked in mouse or human cell lines by decoupling Bmal1 reporter activity from ROR/REV-ERB-dependent transcriptional regulation. We suggest that weak coupling between core and secondary circadian feedback loops accounts for the observed behavior of reindeer fibroblasts in vitro. Our findings highlight diversity in how the thermal environment affects the temporal organization of mammals living under different thermoenergetic constraints.

Assessing the Role of Bacterial Innate and Adaptive Immunity as Barriers to Conjugative Plasmids.

Plasmids are ubiquitous mobile genetic elements, that can be either costly or beneficial for their bacterial host. In response to constant viral threat, bacteria have evolved various immune systems, such as the prevalent restriction modification (innate immunity) and CRISPR-Cas systems (adaptive immunity). At the molecular level, both systems also target plasmids, but the consequences of these interactions for plasmid spread are unclear. Using a modeling approach, we show that restriction modification and CRISPR-Cas are effective as barriers against the spread of costly plasmids, but not against beneficial ones. Consequently, bacteria can profit from the selective advantages that beneficial plasmids confer even in the presence of bacterial immunity. While plasmids that are costly for bacteria may persist in the bacterial population for a certain period, restriction modification and CRISPR-Cas can eventually drive them to extinction. Finally, we demonstrate that the selection pressure imposed by bacterial immunity on costly plasmids can be circumvented through a diversity of escape mechanisms and highlight how plasmid carriage might be common despite bacterial immunity. In summary, the population-level outcome of interactions between plasmids and defense systems in a bacterial population is closely tied to plasmid cost: Beneficial plasmids can persist at high prevalence in bacterial populations despite defense systems, while costly plasmids may face extinction.

Neuromodulation for Neuropathic Pain Syndromes

ABSTRACT OBJECTIVE This article reviews the principles, applications, and emerging trends of neuromodulation as a therapeutic approach for managing painful neuropathic diseases. By parsing evidence for possible mechanisms of action and clinical trial outcomes for various diseases, this article focuses on five common therapy modalities: cutaneous, peripheral nerve, spinal cord, and brain stimulation, and intrathecal drug delivery. LATEST DEVELOPMENTS Recent advances in both invasive and noninvasive neuromodulation for pain have introduced personalized and closed-loop techniques, integrating real-time feedback mechanisms and combining therapies to improve physical and psychosocial function. Novel stimulation waveforms may influence distinct neural tissues to rectify pathologic pain signaling. ESSENTIAL POINTS With appropriate patient selection, peripheral nerve stimulation or epidural stimulation of the spinal cord can provide enduring relief for a variety of chronic pain syndromes. Newer technology using high frequencies, unique waveforms, or closed-loop stimulation may have selective advantages, but our current understanding of therapy mechanisms is very poor. For certain diagnoses and patients who meet clinical criteria, neuromodulation can provide profound, long-lasting relief that significantly improves quality of life. While many therapies are supported by data from large clinical trials, there is a risk of bias as most clinical studies were funded by device manufacturers or insurance companies, which increases the importance of real-world data analysis. Emerging methods like invasive or noninvasive brain stimulation may help us dissect basic mechanisms of pain processing and hold promise for personalized therapies for refractory pain syndromes. Finally, intrathecal delivery of drugs directly to segments of the spinal cord can also modify pain signaling to provide therapy for severe pain syndromes.

EU State aid and the tax allocation of multinationals’ profits

This contribution examines the impact of the EU prohibition of State aid over the tax allocation of multinationals’ profits. All EU Member States apportion the taxable profit of multinational groups in accordance with transfer pricing regulations based on the arm’s length standard, namely, following a market valuation rationale. Although apparently neutral, such a standard may lead to prohibited aid both at the level of its regulatory design and its enforcement. These issues have been recently exacerbated due to the assessment of the “tax rulings” cases, i.e. State aid proceedings opened against the granting of individual, unpublished rulings by certain Member States to some of the largest multinationals operating in the EU, recently reviewed by the ECJ. Unlike most of the scholarly literature, which has focused on the specific issues raised in these cases, this article aims to comprehensively analyse the issues raised by the said regulations when confronted with the EU State aid regime, in line with the latest jurisprudence in this field. The examination starts by defining the aim and contradictions of the arm’s length standard, which is necessary to build a proper reference framework against which deviations resulting in a selective advantage may be detected. Such derogations potentially resulting in prohibited aid may arise when assessing the scope of these regulations, the existence of specific regimes deviating from the arm’s length standard rationale, and in the context of individual administrative acts (e.g. tax rulings) deviating from the content of the applicable transfer pricing regulations.

Adaptive evolution and functional significance of the PPARGC1A gene across diverse animal species.

Codon-based analyses of the PPARGC1A gene across 38 vertebrate species were deployed to elucidate patterns of evolutionary change. Employing maximum likelihood assessments through MEGA, we scrutinized 447 codon positions addressing the entire coding region, excluding positions mired by gaps or missing data. Distinct codons manifested variance in selection pressures, particularly codons 4, 11, 66, and 123, which exhibited positive dN-dS values suggestive of positive selection. Codon 137 displayed the most pronounced dN-dS value, signifying intensified selective advantage. Meanwhile, codons 30 and 90 portrayed near-neutral scores, indicative of purifying selection. Complementary computational methods (IFEL, REL, FUBAR, and SLAC) confirmed positive selection at specific codon sites, with varying degrees of corroboration. The integration of mixed-effect modeling (MEME) identified episodic diversifying selection, pinpointing codons that underwent selection episodes in certain lineages. Refined codon model selection lent insight into substitution rates, revealing nuanced degrees of evolutionary conservation among different codons. Supporting these genetic insights, the phylogenetic analysis highlighted relationships among the PPARGC1A sequences and domain analysis confirmed conserved features across species, while protein-protein interaction networks suggested a complex web of functional interdependencies. These findings advance our understanding of the PPARGC1A gene's evolutionary trajectory and underscore the gene's potential adaptive significance within diverse vertebrate lineages.

Anatomical insights into fish terrestrial locomotion: A study of barred mudskipper (Periophthalmus argentilineatus) fins based on μCT 3D reconstructions.

Mudskippers are a group of extant ray-finned fishes with an amphibious lifestyle and serve as exemplars for understanding the evolution of amphibious capabilities in teleosts. A comprehensive anatomical profile of both the soft and hard tissues within their propulsive fins is essential for advancing our understanding of terrestrial locomotor adaptations in fish. Despite the ecological significance of mudskippers, detailed data on their musculoskeletal anatomy remains limited. In the present research, we utilized contrast-enhanced high-resolution microcomputed tomography (μCT) imaging to investigate the barred mudskipper, Periophthalmus argentilineatus. This technique enabled detailed reconstruction and quantification of the morphological details of the pectoral, pelvic, and caudal fins of this terrestrial mudskipper, facilitating comparison with its aquatic relatives. Our findings reveal that P. argentilineatus has undergone complex musculoskeletal adaptations for terrestrial movement, including an increase in muscle complexity and muscle volume, as well as the development of specialized structures like aponeuroses for pectoral fin extension. Skeletal modifications are also evident, with features such as a reinforced shoulder-pelvic joint and thickened fin rays. These evolutionary modifications suggest biomechanically advanced fins capable of overcoming the gravitational challenges of terrestrial habitats, indicating a strong selective advantage for these features in land-based environments. The unique musculoskeletal modifications in the fins of mudskippers like P. argentilineatus, compared with their aquatic counterparts, mark a critical evolutionary shift toward terrestrial adaptations. This study not only sheds light on the specific anatomical changes facilitating this transition but also offers broader insights into the early evolutionary mechanisms of terrestrial locomotion, potentially mirroring the transformative journey from aquatic to terrestrial life in the lineage leading to tetrapods.

Modelling cultural responses to disease spread in Neolithic Trypillia mega-settlements

As zoonotic diseases coevolved with early agriculture, social distancing within dense human settlements could have conferred a selective advantage in terms of infection risk. Here, we consider the case of Trypillia mega-settlements after 4000 BC, as virulent diseases began affecting humans in the Black Sea region. Through epidemiological susceptible-infected-recovered-susceptible (SIRS) models situated on clustered networks and on a site plan of a Trypillia mega-settlement, we show the adaptive benefits of decreasing either occupation density or the frequency of interactions with other communities across the settlement. We explore critical thresholds in these parameters that may shed light on the fluctuations of population densities at Trypillia mega-settlements before and after approximately 3600 BCE. Our findings suggest that disease was probably a significant driver of human settlement patterns by late Neolithic times.

Inaccuracy principle and dissolution mechanism of lithium iron phosphate for selective lithium extraction from brines

The electrochemical lithiation/delithiation (ELD) method with the typical active materials being LiFePO4 and LiMn2O4, is the next generation technique for the selective lithium extraction from slat-lake brines owning to the advantages of high selectivity and excellent capacity and feasibility. However, the dissolution of LiFePO4/FePO4 (LFP/FP) during the ELD is seldom studied and an inaccurate measurement method for dissolution may result in obtaining an incorrect feasible application range for LFP/FP. Here, electrochemical workstation-electrochemical quartz crystal microbalance (EW-EQCM) is first utilized in the brine system to acquire the in-situ dissolution behavior of LFP/FP redox couple and verify the inaccuracy principle of the dissolution measurement. Both experimental results and thermodynamic calculations demonstrated that the accurate dissolution ratios can only be obtained by iron ions and phosphates at pH < 2.7 and pH < 5.3, respectively, which is induced by the narrow soluble range of iron ions and the formation of Ca5(PO4)3OH and Mg3(PO4)2 precipitation. In addition, the stable pH range of LFP and FP is 4 to 10 and 3 to 5, respectively, and the dissolution is caused by the formation of thermodynamically more stable metal ions, metal ion complexes, and metal ion hydroxides. At the optimum pH, the capacity can maintain 35 mg/g with average dissolution ratios of the cathode and anode lower than 0.1 %. This research sheds light on the accurate dissolution measurement range and method, dissolution mechanism and feasible application range of the LFP/FP redox couple.

Widespread Adaptive Introgression of Major Histocompatibility Complex Genes across Vertebrate Hybrid Zones.

Interspecific introgression is a potentially important source of novel variation of adaptive significance. Although multiple cases of adaptive introgression are well documented, broader generalizations about its targets and mechanisms are lacking. Multiallelic balancing selection, particularly when acting through rare allele advantage, is an evolutionary mechanism expected to favor adaptive introgression. This is because introgressed alleles are likely to confer an immediate selective advantage, facilitating their establishment in the recipient species even in the face of strong genomic barriers to introgression. Vertebrate major histocompatibility complex genes are well-established targets of long-term multiallelic balancing selection, so widespread adaptive major histocompatibility complex introgression is expected. Here, we evaluate this hypothesis using data from 29 hybrid zones formed by fish, amphibians, squamates, turtles, birds, and mammals at advanced stages of speciation. The key prediction of more extensive major histocompatibility complex introgression compared to genome-wide introgression was tested with three complementary statistical approaches. We found evidence for widespread adaptive introgression of major histocompatibility complex genes, providing a link between the process of adaptive introgression and an underlying mechanism. Our work identifies major histocompatibility complex introgression as a general mechanism by which species can acquire novel, and possibly regain previously lost, variation that may enhance defense against pathogens and increase adaptive potential.

A dual-channel fluorescent probe for differential detection of HClO and N2H4

Hypochlorous acid (HClO) and hydrazine (N2H4) are both toxic to the biological environment. The development of a fluorescent probe capable of achieving accurate and sensitive detection of HClO and N2H4 in both organisms and environmental systems is essential to reveal their various physiological and pathological functions. For this work, a dual-channel fluorescent probe PI was developed, which achieved different fluorescence signals in blue and green channels in response to HClO and N2H4 by adjusting the donor and receptor before and after the reaction of fluorophore. PI has the advantages of quick response (12 min for HClO, 15 min for N2H4), good selectivity and high sensitivity for the recognition of HClO and N2H4 in solutions. The probe PI showed good linearity for HClO in the concentration range of 15–50 μM with a limit of detection of 41 nM. It also showed good linearity for N2H4 in the concentration range of 0–200 μM with a limit of detection of 23 nM for N2H4. Furthermore, probe PI was utilized to detect HClO and N2H4 in cells, zebrafish and Arabidopsis thaliana seedlings. The results demonstrate that the probe PI is a promising tool for monitoring HClO and N2H4 in biological systems and the environment.

Fluctuating selection in a monkeyflower hybrid zone

Abstract While hybridization was viewed as a hindrance to adaptation and speciation by early evolutionary biologists, recent studies have demonstrated the importance of hybridization in facilitating evolutionary processes. However, it is still not well-known what role spatial and temporal variation in natural selection play in the maintenance of naturally occurring hybrid zones. To identify whether hybridization is adaptive between two closely related monkeyflower species, Mimulus guttatus and Mimulus laciniatus, we performed repeated reciprocal transplants between natural hybrid and pure species’ populations. We planted parental genotypes along with multiple experimental hybrid generations in a dry (2021) and extremely wet (2023) year in the Sierra Nevada, CA. By taking fine-scale environmental measurements, we found that the environment of the hybrid zone is more similar to M. laciniatus’s seasonally dry rocky outcrop habitat than M. guttatus’s moist meadows. In our transplants hybridization does not appear to be maintained by a consistent fitness advantage of hybrids over parental species in hybrid zones, but rather a lack of strong selection against hybrids. We also found higher fitness of the drought-adapted species, M. laciniatus, than M. guttatus in both species’ habitats, as well as phenotypic selection for M. laciniatus-like traits in the hybrid habitat in the dry year of our experiment. These findings suggest that in this system, hybridization might function to introduce drought-adapted traits and genes from M. laciniatus into M. guttatus, specifically in years with limited soil moisture. However, we also find evidence of genetic incompatibilities in second generation hybrids in the wetter year, which may balance a selective advantage of M. laciniatus introgression. Therefore, we find that hybridization in this system is both potentially adaptive and costly, and that the interaction of positive and negative selection likely determines patterns of gene flow between these Mimulus species.

Dual-emission rare-earth fluorescent nanomaterials for ratiometric and visual detection of N-acetylneuraminic acid and applications in information encryption and anti-counterfeiting

N-acetylneuraminic acid (NANA) can be used as a biomarker for many types of cancers. Currently, there are various methods for detecting NANA but showing some shortcomings that limit the real-time diagnosis of cancer. In contrast, fluorescence analysis has obvious advantages such as low cost, fast response time, and easy operation, and it also enables visual detection for real-time cancer monitoring. Therefore, the establishment of an efficient and rapid detection method is essential for the early prevention and treatment of the disease. Based on the properties of layered rare-earth hydroxide (LRH), we synthesized a dual-emission fluorescent material (NDC/SDS-LEuH), and further fabricated a fluorescent nanoprobe (ANP) for the detection of NANA. The probe has the advantages of high sensitivity (LOD = 32.9 μM) and high selectivity with fast response. During the sensing process, the dual emission of the probe shows opposite changes due to the photoinduced electron transfer (PET) effect and the interaction between NANA and the probe. The color changes of the system can be observed under UV irradiation. Therefore, a visual platform was developed to detect NANA with a LOD of 0.09 mM. In addition, a probe hydrogel was prepared, which can be applied in the anti-counterfeiting to improve the difficulty of counterfeiting and the security of anti-counterfeiting. The probe achieves ratiometric fluorescence detection of NANA, which reduces background interference and improves the accuracy of detection. A visual detection platform was fabricated to realize the real-time detection. In addition, the prepared probe hydrogel showed the potential applications in anti-counterfeiting, which provided new ideas for the design and application of anti-counterfeiting materials.

Manipulation of natural transformation by AbaR-type islands promotes fixation of antibiotic resistance in Acinetobacter baumannii

The opportunistic pathogen Acinetobacter baumannii, carries variants of A. baumannii resistance islands (AbaR)-type genomic islands conferring multidrug resistance. Their pervasiveness in the species has remained enigmatic. The dissemination of AbaRs is intricately linked to their horizontal transfer via natural transformation, a process through which bacteria can import and recombine exogenous DNA, effecting allelic recombination, genetic acquisition, and deletion. In experimental populations of the closely related pathogenic Acinetobacter nosocomialis, we quantified the rates at which these natural transformation events occur between individuals. When integrated into a model of population dynamics, they lead to the swift removal of AbaRs from the population, contrasting with the high prevalence of AbaRs in genomes. Yet, genomic analyses show that nearly all AbaRs specifically disrupt comM, a gene encoding a helicase critical for natural transformation. We found that such disruption impedes gene acquisition, and deletion, while moderately impacting acquisition of single nucleotide polymorphism. A mathematical evolutionary model demonstrates that AbaRs inserted into comM gain a selective advantage over AbaRs inserted in sites that do not inhibit or completely inhibit transformation, in line with the genomic observations. The persistence of AbaRs can be ascribed to their integration into a specific gene, diminishing the likelihood of their removal from the bacterial genome. This integration preserves the acquisition and elimination of alleles, enabling the host bacterium-and thus its AbaR-to adapt to unpredictable environments and persist over the long term. This work underscores how manipulation of natural transformation by mobile genetic elements can drive the prevalence of multidrug resistance.

Attention as selection for action defended

AbstractAttention has become an important focal point of recent work in ethics and epistemology, yet philosophers continue to be noncommittal about what attention is. In this paper, I defend attention as selection for action in a weak form, namely that selection for action is sufficient for attention. I show that selection for action in this conception captures how we, the folk, experience it and how the cognitive scientist studies it. That is, selection for action pulls empirical and folk‐psychology together. Accordingly, philosophers who take seriously either source have reason to work with selection for action as their starting conception of attention. This conception provides a way to bridge empirical and philosophical concerns where attention is central. The theoretical advantages of selection for action have been obscured by the common opinion that it is easily refuted. I defend the position against many of the published objections and then deploy it to provide a foundation for the intuitive, but inchoate, idea of attention being gradable, something of which there can be more or less. An analysis of the gradability of attention is then applied to consider recent work on the harms due to a surplus of attention.

Yawning In Sync: Implications For Social Cohesion In Horses

Abstract The increasing interest in the study of spontaneous (SY) and contagious yawning (CY) was so far focussed on several taxa, especially primates. Here, we focused on SY and CY in horses, a suitable species due to their complex social dynamics that has been largely overlooked in research on these phenomena. By analysing videos of 48 horses on pasture, we identified two yawning morphologies: Covered (YCT) and Uncovered Teeth (YUCT). Using EquiFACS, we quantitatively demonstrated that YCT and YUCT differ in terms of muscle recruitment. Moreover, we provide the first evidence for the presence of CY by comparing two different conditions: chewing-yawn-chewing versus chewing-chewing-chewing. Supporting the Social Modulation hypothesis, in our mares, CY was more prominent among subjects sharing good relationships. Moreover, subjects responded more rapidly to kin compared to non-kin and kin frequently grooming each other responded even more rapidly to each other yawns. The high familiar yawn sensitivity can provide selective advantages increasing behavioural synchronization and group cohesion.

Persistent Educational Advantages of Asian Immigrants’ Children, 1940 to 2015–2019

The educational achievements of Asian American children, especially those from lower backgrounds, are substantially higher than other ethnoracial groups. Hyper-selectivity theory finds the origin of such an advantage in the double selectivity of Asian immigrants after the passage of the 1965 Immigration Act and the formation of cross-class community resources. Utilizing the 1940 linked full-count Census, 1940–2000 decennial censuses, and the 2008–2012 and 2015–2019 American Community Survey, this study tracks changes in the educational advantages of Asian immigrants’ children. Our results show that in contrast to the anticipated dependence of the educational achievements of Asian immigrants’ children on structural conditions, the educational advantages of Asian immigrants’ children have remained remarkably persistent over time and across geographical locations. The influx of highly educated Asian immigrants is not associated with an increase in the educational advantages of lower-background Asian Americans. The implications of these findings are discussed.

Efficient removal and recovery of lead from high arsenic antimony oxide powder

The existence of Pb in crude antimony oxide powder(CAOP) hinders the further smelting and recovery of Sb and leads to some environmental problems. Therefore, the selective removal of Pb from CAOP is important for the production of high-purity antimony products. In this work, Pb in CAOP is removed by HNO3 leaching, achieving purification of CAOP. Then H2SO4 is used to recover Pb from the HNO3 leaching solution. The Pb leaching efficiency reaches 98.9 %, resulting in a decrease in the Pb content from 4.56 % to 0.20 % in CAOP. The Sb leaching efficiency is controlled at around 5.0 %. These confirm HNO3 has good selectivity. The HNO3 disrupts the molecular structure of the raw materials during the leaching, resulting in the conversion of Sb2O3 and As2O3 into insoluble AsSbO4. By adding H2SO4 to the leaching solution, the Pb precipitation efficiency reaches 93.6 %. After Pb removal, the leaching solution can be re-used for the leaching of Pb, while the residue can be directly returned to the pyrometallurgical system. The reaction mechanism and a novel approach for removing Pb from CAOP are proposed, which have the advantages of high selectivity, effective Pb separation, and recoverable HNO3.

Chitosan based fluorescent probe with AIE property for detection of Fe3+ and bacteria

Fluorescent probe with aggregation-induced emission (AIE) property has been widely used because of the advantages of high sensitivity, good selectivity and non-destructive testing. The development of fluorescent probe with good biocompatibility, photostability and biodegradability is of great significance in biomedicine and environmental detection. Herein, a novel type of fluorophore CS-TPE for detection of Fe3+ and bacteria was prepared by the Schiff base reaction of chitosan (CS) and 4-(1,2,2-triphenylethenyl) benzaldehyde (TPE-CHO). The fluorescence response mechanism of CS-TPE system was investigated by various characterization techniques. CS-TPE had an obvious AIE behavior with strong blue-green emissions at 473 nm and reaches the highest photoluminescence (PL) emission in 90 % H2O/ethanol mixtures. CS-TPE fluorescent probe exhibited sensitive quenching response to Fe3+, which can be used as a biosensor for detecting the concentration of Fe3+ with short response time (5 min), low detection limit (0.998 μM) and wide detection range (10–300 μM). Meanwhile, CS-TPE exhibited good antibacterial performance for S. aureus and E. coli. It is expected to realize the real-time fluorescence monitoring of metal ion detection and antibacterial process.

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.