Elongated tails are exaggerated ornaments observed in various bird species, and their functional and evolutionary dynamics have attracted considerable attention. Empirical studies consistently show that sexual selection is a major drive of tail elongation. However, the genetic basis of this trait remains poorly understood. To address this gap, we performed comparative genomic analyses of 23 bird species, including 7 with extremely long tails and 16 with relative short tails. Genes related to feather development exhibited amino acid convergence replacement (e.g., APC) or displayed faster evolutionary rates (e.g., LEF1, WISP3) in the long-tailed species. Importantly, we identified convergence replacements of amino acids and rapid evolution in genes related to reproductive functions (e.g., PAQR7) and immunity (e.g., ADA), suggesting that elongated tails may serve as honest signals of genetic quality. In conclusion, this study provides genomic evidence supporting the role of sexual selection in the evolution of elongated tails, revealing an intricate interplay between sexually selected traits, fitness, and immune competence.

Evolution of SAMD9 and SAMD9L genes in primates: a complex history of gene loss, gene duplication and pseudogenization.

Circulating tumor DNA (ctDNA) analysis has emerged as a powerful and minimally invasive approach for genomic profiling of metastatic castration-resistant prostate cancer (mCRPC), enabling real-time detection of tumor-derived mutations that guide therapy. Approximately 20% of mCRPC patients harbor alterations in homologous recombination repair (HRR) genes, most commonly BRCA1/2 and ATM, which are actionable with different poly-(ADP-ribose) polymerase inhibitors (PARPIs) used as monotherapy or in combination with androgen receptor signaling inhibitors (ARSIs). A smaller subset of patients with mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-high) tumors may benefit from immune checkpoint blockade with pembrolizumab. Different FDA-approved liquid biopsy assays detect these actionable alterations when tissue biopsies are unavailable or insufficient. This review summarizes current evidence on ctDNA-based genotyping in mCRPC, highlighting clinically actionable mutations, corresponding targeted therapies, and technical and analytical considerations for clinical implementation. By capturing DNA shed from multiple metastatic sites, ctDNA profiling provides a comprehensive view of tumor heterogeneity and enables serial monitoring of molecular evolution. Overall, ctDNA analysis represents a transformative advance in precision oncology, supporting personalized treatment selection and ongoing assessment of therapeutic response in mCRPC.

The adaptation to terrestrial environments from aquatic environments has always been regarded as a major evolutionary transition in fishes, during which it has been accompanied with diverse phenotypic innovations. Mitochondrial energy metabolism fundamentally enables this shift, but the evolutionary trajectory and molecular mechanisms of mitogenomic adaptations to energy demands are poorly characterized. Mudskippers, a group of gobies with amphibious adaptive traits, serve as ideal models for studying energy metabolism during the water-to-land transition. To test whether amphibious adaptation in gobies corresponds to adaptive evolution in mitochondrial OXPHOS genes, we performed an in silico analysis of the 13 OXPHOS genes from the mitochondrial genomes of 33 goby species and two outgroups. The results showed that: (1) No matter ML or BI methods, four subfamilies Amblyopinae, Gobiinae, Gobionellinae, Oxudercinae are paraphyletic origin, except for subfamily Sicydiinae; besides, genus Scartelaos was first confirmed that it is paraphyletic origin. (2) 13 OXPHOS genes have been under the strong selective constraints, yet, the episodic positive selection was also detected, and ND4 and ATP8 evolution has been found to be under the accelerated evolution. Interestingly, (3) Significant divergent selection was detected between amphibious and fully aquatic lineages in 11 of the 13 OXPHOS genes (84%). And (4) the much stronger selective constraints were uncovered in amphibious lineages. To sum up, OXPHOS genes have undergone adaptive evolution with notable divergent patterns associated with the water-to-land transition during transition from water to land. These results provided some new insights into the genetic basis of amphibious adaptation in goby.

The exon junction complex (EJC) is a central mediator of post-transcriptional regulation in eukaryotes. A comprehensive, systematic analysis of EJC core genes has been lacking in Phyllostachys edulis (P. edulis). Here, we identified 147 EJC core genes across 17 plant species spanning the major green plant lineages. Phylogenetic analyses supported each family as a monophyletic clade consistent with established taxonomic relationships. Synteny analyses indicated that segmental duplication is the principal driver of EJC core gene expansion in P. edulis (Moso bamboo). Transcriptome profiling further showed that nearly all PedEJCs were engaged during rapid shoot growth, with PedY14b-D, PedY14c-D, and PedY14d-C displaying the most pronounced expression changes. During shoots’ post-harvest senescence process, PedEIF4A3s, PedY14s, and PedMAGOs were progressively downregulated, whereas PedBTZs were upregulated, indicating distinct module-level responses among EJC subunits. Only a small subset of PedEJCs responds to phytohormones and abiotic stresses. Furthermore, cis-regulatory element composition in promoter region likely shapes PedEJCs transcriptional regulation. Collectively, these findings lay the groundwork for in-depth functional dissection of PedEJCs in Moso bamboo.

Despite improvements in the molecular profiling of pancreatic neuroendocrine tumors (PanNETs), predicting their clinical behavior and response to specific therapies remains challenging. We sought to elucidate the molecular basis underlying the broad phenotypic variations in these neoplasms through a genetic characterization of primary and metastatic PanNETs. Our findings revealed an enrichment of CDKN2A homozygous deletions and TSC2 somatic mutations in metastatic PanNETs when compared to non-metastatic lesions. Tumor evolution analysis further revealed the acquisition of such genetic alterations as late events in the progression of these neoplasms, conferring poor survival outcomes to the affected patients. Biallelic loss of DNA damage repair genes, ATRX and/or DAXX, was associated with a high fraction of the genome altered in PanNETs, with pathogenic alterations affecting those genes also being associated with a homologous recombination deficiency signature. These findings highlight molecular mechanisms driving PanNET progression and underscore the need for further molecular characterization and tumor evolution studies to evaluate targeted therapies for such a challenging disease.

Abstract What are the implications of evolution for cancer epidemiology? Cancers develop through a process of cellular evolution, constrained and shaped by the evolution of the organisms in which they grow. Furthermore, diet, exercise, exposures and the constitutive genotypes of the hosts impact the cellular evolution that drives neoplastic progression and cancer’s response to interventions. An evolutionary approach to cancer epidemiology helps to bridge scales from the molecular causes of cancer and cellular dynamics up to population level phenomena. Until recently, there has been little consideration of the implications of evolution for cancer epidemiology. In April 2025, we held the first workshop on evolutionary cancer epidemiology. We identified at least six ways in which organismal evolution impacts cancer epidemiology: 1) Organismal evolution has led to the evolution of cancer genes in the germline, 2) population bottlenecks have led to the spread of cancer risk alleles like BRCA1 mutations, 3) some species have evolved extremely low cancer rates which may illuminate new mechanisms of cancer suppression, while species with extremely high cancer rates may help us learn about cancer susceptibility, 4) organismal evolution has likely involved tradeoffs between cancer risk and other selective pressures, 5) changes in our environments have led to evolutionary mismatches between our ancestral environments and modern environments, and 6) co-evolution of human biology with microbes have impacted cancer incidence. We also identified at least five ways in which cell level evolution impacts cancer epidemiology: 1) Multiscale models of cell level dynamics help explain cancer incidence patterns, 2) exposures change the selective pressures on somatic cells, 3) the germline genotype also affects the selective pressures and mutational processes in somatic cells, 4) the stochastic and spatially heterogeneous nature of cell level evolution impact the success of cancer screening and biomarkers, and 5) many exposures leave a signature of their role in the types of mutations they cause, allowing us to infer their role in any given tissue. Previous work on all of these topics have demonstrated the power and utility of this approach. The inclusion of evolutionary theory and tools in cancer epidemiology holds the promise of improving cancer risk prediction, prevention, disparities, and management. It may also help to understand the rise in early onset cancers and help to improve cancer screening and clinical trial design. The critical barrier to progress is only a lack of cross-training and collaborations between evolutionary biologists and cancer epidemiologists. We hope to rectify that. Citation Format: Carlo Maley, Katherine Lawson-Michod, Hannah Carter, Kathleen Curtius, Kathleen Houlahan, Nic Fisk, Li Liu, Joseph Lachance, James DeGregori, Charles Swanton, Zachary T. Compton, Athena Aktipis, Robert Hiatt, Arcadi Navarro. Evolutionary cancer epidemiology [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr IA007.

Sexual conflict is pervasive and can favor the evolution of differential gene expression patterns between males and females. The evolution of such sex-biased expression patterns is constrained by pleiotropic functions of differentially expressed genes, such as widespread expression across tissues. We investigated sex-biased gene expression and its relationship to tissue specificity in reproductive and somatic organs in the Northern pipefish, Syngnathus fuscus, a polygynandrous species with extreme paternal care and no evidence of sex chromosomes - conditions ripe for intra-locus sexual conflict. We found patterns of sex-biased expression in the gonads, liver, and gills of the Northern pipefish, with the largest number of sex-biased genes identified in the gonads. In general, sex-biased genes were only more tissue-specific in the reproductive tissues (gonads), but not in either of the somatic tissues (liver or gills). Sex-biased genes with evidence of branch-specific selection were also more tissue specific. We highlight the potential for different sex-specific selection pressures to be acting on each tissue type as there were widespread differences in the protein classes represented by sex-biased genes across both organs and sexes, although sex-biased genes did not experience stronger episodic selection than unbiased genes. Furthermore, our results support the hypothesis that broad expression can constrain the molecular evolution of a gene. The work presented here supports the potential for sex-biased gene expression to act as a mechanism for phenotypic differentiation between the sexes and increases our knowledge of patterns of gene expression in an unusual group of fishes.

Histidine phosphotransfer proteins (HP/Hpts) are key components in the two-component system (TCS) involved in cytokinin signalling. In rice, five Hpt genes have been identified, including two authentic and three pseudo-Hpts. This study focused on isolating and characterizing the OsHpt4/PHP2-like gene from three O. indica rice varieties, and on exploring the evolutionary and regulatory features of the Hpt gene family across Oryza species. Hence, we isolated the OsHpt4/PHP2-like gene (456bp; 151 amino acids) from three O. indica rice varieties- ASD-16 (Parentage- ADT 31/Co39), ADT-54 (Parentage-I.W.Ponni/ Banskathi) and CO-52 (Parentage- BPT 5204/ Co (R) 50) and compared their physicochemical properties. To gain broader insights, a genome-wide analysis was conducted across six Oryza species (Oryza sativa ssp. japonica, Oryza sativa ssp. indica, Oryza rufipogon, Oryza nivara, Oryza glumaepatula, and Oryza barthii), identifying 35 Hpt isoforms. Studies on gene structure and conserved motifs showed that intron and exon organization, as well as motif composition, are well preserved. Phylogenetic analysis grouped Hpts into four main clusters with other monocots. Both segmental and tandem gene duplications contributed to gene family expansion. Promoter analysis revealed cis-elements responsive to phytohormones, abiotic stresses, light, and development. These results offer new insights into the evolution and regulation of Hpt genes in rice, and it paves a strong avenue for future research on stress tolerance and crop improvement.

Annexins are a diverse family of calcium-dependent phospholipid-binding proteins involved in membrane transport, signal transduction, and various stress responses in plants. This study presents a comprehensive phylogenetic analysis of annexin genes across multiple monocot and dicot plant species. The study involved downloading the complete annexin gene sequences from reliable databases. Phylogenetic trees were carefully constructed for individual plant species, followed by a comparative analysis that distinguished the evolutionary approach of annexin genes among monocots and dicots. The analysis revealed significant evolutionary divergence and conserved clades within the annexin gene family, suggesting both lineage-specific expansions and ancient gene duplications. The results of this study provide new insights into the molecular evolution of annexins and highlight their potential role in plant adaptation and resilience. The comprehensive phylogenetic analyses performed in this work not only contribute to the understanding of annexin gene evolution but also lay the foundation for future functional studies aimed at exploiting annexins for crop improvement and stress management.

ABSTRACT In this study, four metal complexes [VL (phen)], [RuL (phen)], [VL (bpy)] and [RuL (bpy)]—were synthesized and structurally characterized using comprehensive analytical and spectral techniques. Density functional theory (DFT) calculations (B3LYP) were employed to examine their electronic properties and reactive sites, while molecular docking studies revealed strong hydrogen‐bonding interactions of the furan, thiazole, bipyridine, and phenanthroline moieties with Mpox and COVID virus receptor proteins. Key metal–ligand interactions, notably oxygen coordinated to vanadium and chlorine coordinated to ruthenium, exhibited high binding affinity. In silico ADMET profiling indicated drug‐like properties but also highlighted potential limitations in oral bioavailability due to high molecular weight, lipophilicity and low solubility. To enhance predictive modelling, a molecular gradient evolution optimizer (MoGEO)—driven artificial neural network (ANN) framework was developed, integrating molecular energy shifts and docking interaction data into the learning process. The ANN‐MoGEO approach achieved superior accuracy in predicting synthesis yields, docking scores and spectral peaks, outperforming conventional optimizers. These findings not only deepen the understanding of Ru (III) and V(V) complexes but also demonstrates ANN‐MoGEO's potential as a powerful tool for molecular property prediction in drug design.

Comparative genomic analyses among closely related species provide an opportunity to assess their evolutionary history. The relatedness between species can depend on a variety of factors, including reproductive isolation, introgression, and incomplete lineage sorting, and this can impact divergence across the genome. Here, we use a combination of long- and short-read sequencing and HI-C scaffolding to assemble genomes for each of the four species in the testacea species group of Drosophila, including D. testacea, D. orientacea, D. neotestacea, and D. putrida, and its outgroup, D. bizonata. First, among species we find many structural rearrangements across the genome as well as a large size difference in the dot chromosome that we infer is due to expansion of repetitive elements. Second, we assess phylogenetic discordance and uncover a difference in the phylogeny inferred from genes on Muller E and the mitogenome relative to the rest of the genome, which may be due to recent hybridization. Lastly, we assess the rate of molecular evolution of genes shared across all species and identify genes evolving at different rates across the phylogeny. Our results present genomic resources for this species group and begin to probe into some of the evolutionary characteristics that contribute to variation in genome structure, while highlighting the need for high-quality genome resources to fully capture and understand the evolutionary history among closely related species.

The nucleotide-binding site (NBS) gene family is central to plant innate immunity. However, a comprehensive understanding of its evolutionary dynamics and functional diversity in maize, particularly within a pan-genomic context, remains limited. We conducted a systematic pan-genomic analysis of the ZmNBS gene family across 26 representative maize inbred lines. Our approach integrated evolutionary genetics, structural variation analysis, and expression profiling to investigate presence-absence variation (PAV), duplication modes, evolutionary rates, and the impact of structural variants (SVs). We observed extensive presence–absence variation (PAV), distinguishing conserved “core” subgroups (ZmNBS31 and ZmNBS17-19) from highly variable ones (ZmNBS1-10 and ZmNBS43-60), thereby supporting a “core-adaptive” model of resistance gene evolution. Duplication mode analysis revealed subtype-specific preferences: canonical CNL/CN genes largely originated from dispersed duplications, while N-type genes were enriched in tandem duplications. Evolutionary rate analysis showed that whole-genome duplication (WGD)-derived genes exhibited strong purifying selection (low Ka/Ks), whereas tandem and proximal duplications (TD/PD) showed signs of relaxed or positive selection. Structural variants (SVs) were associated with altered motif structures and significantly impacted gene expression. Notably, ZmNBS31 emerged as a conserved, highly expressed gene under both stressed and control conditions, underscoring its potential role in basal immunity. Our findings demonstrate how duplication mechanisms, structural variations and differential selection pressures collectively shape the evolution of the ZmNBS gene family. The identification of ZmNBS31 as a candidate for basal immunity, along with our established "core-adaptive" framework, provides valuable insights and a conceptual foundation for identifying and improving broad-spectrum resistance genes in maize breeding programs.

Phylogenomics provides insights into the phylogeny of Liliales and the evolution of colchicine biosynthesis genes.

The neutral theory of molecular evolution, positing that most amino acid substitutions in protein evolution are neutral, is supported by vast comparative genomic data. However, here we report that the key premise of the theory-beneficial mutations are extremely scarce-is violated. Deep mutational scanning data from 12,267 amino acid-altering mutations in 24 prokaryotic and eukaryotic genes reveal that > 1% of these mutations are beneficial, predicting that > 99% of amino acid substitutions would be adaptive. This observation demands a new theory that is compatible with both the high beneficial mutation rate and the comparative genomic data considered consistent with the neutral theory. We propose such a theory named adaptive tracking with antagonistic pleiotropy. In this theory, virtually all beneficial mutations observed are environment specific. Frequent environmental changes and mutational antagonistic pleiotropy across environments render most of the beneficial mutations seen at one time deleterious soon after and hence rarely fixed. Consequently, despite the occurrence of adaptive tracking-continuous adaptation to a changing environment fuelled by beneficial mutations-neutral substitutions prevail. We show that this theory is supported by population genetics simulation, empirical observations and experimental evolution and has implications for the adaptedness of natural populations and the tempo and mode of evolution.

Antibodies play a crucial role in adaptive immunity. They develop as B cell receptors (BCRs): membrane-bound forms of antibodies that are expressed on the surfaces of B cells. BCRs are refined through affinity maturation, a process of somatic hypermutation (SHM) and natural selection, to improve binding to an antigen. Computational models of affinity maturation have developed from two main perspectives: molecular evolution and language modeling. The molecular evolution perspective focuses on nucleotide sequence context to describe mutation and selection; the language modeling perspective involves learning patterns from large data sets of protein sequences. In this paper, we compared models from both perspectives on their ability to predict the course of antibody affinity maturation along phylogenetic trees of BCR sequences. This included models of SHM, models of SHM combined with an estimate of selection, and protein language models. We evaluated these models for large human BCR repertoire data sets, as well as an antigen-specific mouse experiment with a pre-rearranged cognate naive antibody. We demonstrated that precise modeling of SHM, which requires the nucleotide context, provides a substantial amount of predictive power for predicting the course of affinity maturation. Notably, a simple nucleotide-based convolutional neural network modeling SHM outperformed state-of-the-art protein language models, including one trained exclusively on antibody sequences. Furthermore, incorporating estimates of selection based on a custom deep mutational scanning experiment brought only modest improvement in predictive power. To support further research, we introduce EPAM (Evaluating Predictions of Affinity Maturation), a benchmarking framework to integrate evolutionary principles with advances in language modeling, offering a road map for understanding antibody evolution and improving predictive models.

Transitions toward simplified life cycles can reshape evolutionary trajectories, yet their impact on the rate of molecular evolution remains poorly understood. In aphids, host alternation (heteroecy) entails obligate seasonal migration between highly distinct plant hosts - typically woody and herbaceous species - and has been repeatedly lost, giving rise to monoecious species with simplified life cycles. Using comparative genomics across 46 aphid species, we tested whether transitions from heteroecy to monoecy alter evolutionary dynamics at the gene level. We identified 9,304 orthologs and estimated evolutionary rates (dN/dS) and shifts in selection regimes in the diverse Aphidinae subfamily. We found that 715 orthologs evolved faster in monoecious species, primarily due to relaxed selection, while heteroecious species showed signatures of intensified selection. Genes under relaxed selection in monoecious species were enriched for functions related to environmental sensing, signaling, nutritional adjustments, morph determination and migration related - traits likely central for host alternation. These results suggest that the loss of a complex life cycle leads to reduced selective constraints as a consequence of ecological simplification. This study provides a robust evolutionary framework for understanding how life cycle transitions shape molecular evolution and drive gene decay following trait loss.

Epistatic drift in protein evolution.

Evolution of the animal globin superfamily: Insights from the blood clam Anadara granosa.

Carbapenemase-producing Pseudomonas aeruginosa (CRPA) poses a significant challenge to the effectiveness of antimicrobial therapy in patients, further complicated by the emergence of colistin resistance (CLR). This study aimed to provide molecular epidemiological insights into clinical P. aeruginosa strains that produce carbapenemases and exhibit CLR. A total of fifty clinical isolates of CRPA were collected from Milad Hospital in Tehran, Iran. Antimicrobial susceptibility testing and colistin broth disk elution were performed to determine the resistance patterns. PCR assays were conducted to investigate the prevalence of resistance-associated genes, including blaKPC, blaIMP, blaVIM, blaOXA-48, blaNDM, and mcr-1 to -10. Molecular typing using pulsed-field gel electrophoresis (PFGE) was employed to determine the relationship between strains and assess their spread. The study showed that 94% of the tested strains were resistant to imipenem, and 92% were resistant to meropenem. CLR (MIC ≥ 4µg/L) was observed in 14 isolates (28%) using the broth disk elution method, 84% isolates were identified as XDR. The most prevalent carbapenemase identified was the IMP enzyme, present in 24 strains (48%), followed by the VIM, NDM, KPC, and OXA-48 detected in 12 (24%), 5 (10%) and 2 (4%) isolates, respectively. Additionally, the mcr-1 gene was detected in 8% of the isolates, and a co-occurrence of the mcr-1 and mcr-3 genes was observed in 2% of the isolates. No other mcr genes were detected in the studied isolates. All isolates were grouped under eight clusters (A-H). The major one was related to the A cluster with 19 isolates. This study reports, for the first time, the co-occurrence of the mcr-1 and mcr-3 genes. To mitigate the spread of resistant P. aeruginosa and prevent the further evolution of mcr genes, it is crucial to enhance surveillance efforts, strictly adhere to infection prevention protocols, and practice antibiotic stewardship. These measures are essential for controlling the transmission of drug-resistant P. aeruginosa strains and preserving the effectiveness of available treatment options.