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Biology subjects

Wen, M.

Publications and source records attributed to Wen, M..

At least 19 recordsLinked to original sources

Flavonoid chronotherapy normalizes circadian dynamics and sleep architecture in mice with painful nerve injury

Neuropathic pain (NP) is linked to disrupted sleep and circadian abnormalities upon painful peripheral nerve injury. By performing spared nerve injury (SNI) in circadian reporter PER2::LUC mice, we characterized the real-time changes in rhythmicity of the core clock gene Per2 in the pain-regulating dorsal root ganglia (DRG), and the sleep-wake cycle using wireless EEG/EMG under NP conditions. We further evaluated whether the clock-resynchronizing flavonoids, nobiletin (2 mg/kg/day) and tangeretin (1.8 mg/kg/day), administered continuously via osmotic minipumps for two weeks, could restore circadian dynamics and alleviate pain-related behaviour. Both flavonoids alleviated SNI-induced dynamic hypersensitivity in PER2::LUC mice on post-surgical day 14. SNI increased the amplitude of Per2 rhythms in the DRGs, which was restored to pre-surgical levels by administration of flavonoids. In addition, tangeretin showed sleep-restoring properties upon SNI by alleviating disturbances in NREM sleep and wakefulness. These results support targeting circadian disruption as a potential chronotherapeutic approach to alleviate NP.

neuroscience↗

Sex specificity of inhibitory gating deficits in individuals with high autistic traits

Empirical evidence from traditional inhibitory control tasks regarding inhibitory deficits in high autistic traits has been mixed, indicating that this issue remains controversial. Although sex differences are widely documented in autistic cognitive profiles, their role in inhibitory gating mechanisms remains underexplored. Given that the expression of inhibitory gating deficits may be modulated by the social versus non-social nature of stimuli, and no prior study has investigated this topic by integrating both sex differences and stimulus domain, we addressed these two questions with the attribute amnesia paradigm. We manipulated stimulus type (non-social vs. social). In Experiment 1, participants performed a location task with animal drawings as targets and were unexpectedly asked to report animal identity on a surprise trial. High autistic trait females showed significantly higher accuracy on the surprise trial than all other groups, reflecting a failure to actively filter out task-irrelevant non-social information, that is, a reduced inhibitory gating efficiency. In Experiment 2, using face stimuli and a self-vs. other-face design, this gating deficit was no longer expressed: all groups performed at chance levels on the identity judgment, regardless of autistic trait level, sex, or face type. This dissociation aligns with a dual-mechanism framework: the inhibitory gating deficit in high autistic trait females is specific to non-social stimuli and masked by camouflaging for social ones. This study demonstrates that the inhibitory gating deficit in high autistic trait females is not a global impairment but rather a stimulus-dependent one, highlighting the need to consider sex and stimulus type.

neuroscience↗

Selective encoding failure of self-face identity in subthreshold depression

Subthreshold depression is associated with significant functional impairment and elevated risk of major depressive disorder. A negative self-concept may disrupt the implicit positive association evoked by ones own face, impairing incidental encoding of self-relevant information. Whether subthreshold depression involves a selective deficit in encoding self-face identity remains unclear. The attribute amnesia paradigm is well suited to address this question because it can dissociate attentional selection from working memory encoding. Using this paradigm, we examined the issue across two experiments. Experiment 1 employed nonsocial stimuli (animal drawings) and confirmed an intact attribute amnesia effect in subthreshold depression (n = 30) comparable to healthy controls (n = 30), ruling out a generalized encoding deficit. Experiment 2 replaced targets with faces (self or other) and revealed a selective enhancement of the attribute amnesia effect for self-face identity in subthreshold depression. Specifically, on the surprise trial, accuracy for self-face identity dropped to near-chance levels in the subthreshold depression group, whereas no such deficit emerged for other-faces or in controls. Encoding recovered rapidly once explicit memory expectations were introduced, indicating intact basic encoding capacity. These findings suggest that subthreshold depression is associated with a specific impairment in incidentally encoding self-face identity. This impairment likely stems from a negative self-concept that weakens self-face salience under incidental encoding conditions. By capturing this selective encoding failure, the present study reveals that the self-processing deficit in subthreshold depression can arise at the gating stage between attention and working memory consolidation.

neuroscience↗

From ambiguous object to illusory faces: EEG decoding reveals a dynamic cascade of face pareidolia

Face pareidolia, perceiving faces in inanimate objects, provides a unique window into how the brain constructs perceptual meaning from ambiguous visual input. In this work, we investigated the neural dynamics of face pareidolia, testing the hypothesis that it emerges from a temporal cascade that integrates global (low spatial frequency, LSF) and local (high spatial frequency, HSF) visual information. With a pareidolia detection task, we combined event-related potentials (ERP), multivariate pattern analysis (MVPA), and representational similarity analysis (RSA) to map the evolving neural code for illusory face perception. Behaviorally, participants experienced pareidolia from both LSF and HSF stimuli, but the percept was strongest for broadband images containing both frequency bands. Electrophysiological results revealed a clear temporal progression. Early processing (<150 ms) was driven by low-level attributes, with distinct P100/N100 components and neural representations for LSF and HSF signals. A critical shift occurred around 145 ms, after which MVPA decoding could reliably distinguish between images perceived as faces and those that were not. Concurrently, RSA showed that the geometry of neural representations shifted to reflect participants subjective face-likeness ratings, rather than the initial physical properties of the stimuli. This transition to a higher-order, subjective evaluation was marked by a later N250 component, whose amplitude indexed the cognitive load of integrating the visual cues. Together, these findings demonstrate that face pareidolia is a dynamic neural cascade, from early sensory encoding to higher-order perceptual evaluation, driven by the integration of global configuration and local features of visual stimuli. Our results illuminate how the brain transforms ambiguous input into meaningful social perception, offering insight into the temporal dynamics of visual awareness.

neuroscience↗

Spatiotemporal Regulatory Logics of Mouse Gastrulation

Spatiotemporal coordination of cellular and molecular events is crucial for cell fate commitment during mouse gastrulation. However, the high-precision mechanisms governing the timing and spatial dynamics remain poorly understood. Here, we present a time-series single-cell multi-omic dataset from the mouse gastrulating embryos and construct a hierarchical gene regulatory landscape. Integrating this with real three-dimensional transcriptomic coordinate, we created ST-MAGIC and ST-MAGIC (+) atlas, dissecting the spatiotemporal logics of regulatory networks and signaling responsiveness underpinning the lineage commitment at gastrulation. Specifically, we delineated the multi-omic basis for left-right symmetry breaking events in the gastrula and also revealed the spatiotemporal molecular relay for axial mesendoderm lineage, where early and intermediate transcription factors first open the chromatin regions and setup the responsiveness to signaling, followed by terminal factors to consolidate the transcriptomic architecture. In summary, our study presents a spatiotemporal regulatory logic framework of mouse gastrulation, that advances our understanding of mammalian embryogenesis.

developmental biology↗

The transcripts of a gastrula-premarked enhancer prime posterior tissue development through cross-talk with morphogen effector

The regulatory mechanisms governing cell fate determination, particularly lineage diversification during mammalian embryonic development, remain poorly understood with in-depth regulatory paradigms yet to be fully elucidated. Here, leveraging the epigenetic landscape of mouse gastrula, we identified p-Enh, a pre-marked enhancer in primitive streak region, as pivotal regulator for posterior tissue development in mouse embryos. Morphological and single-cell transcriptomic analyses confirmed embryonic lethality phenotype with disrupted posterior tissue development trajectories in p-Enh-KO embryos. Molecularly, apart from regulating the neighboring coding-gene Cdx2 in cis, our findings suggest that p-Enh also modulate the global transcriptome and epigenomic landscape, which might through the transient production of eRNA in trans. Further investigation revealed p-Enh participate in the regulatory cascades of TGF-{beta} signaling. Chemical modulation of TGF-{beta} signaling can largely rescue the posterior development deficiency in in vitro gastruloids through a Cdx2-independent mechanism. Thus, we propose a potential model in which the broadly distributed p-Enh transcripts within the nucleus could serve as essential cross-modular coordinators, priming the posterior development of mouse embryo.

developmental biology↗

Genomic locus of lncRNA-Gm26793 forms an inter-chromosomal molecular lock with Cubn to ensure proper stem cell differentiation and mouse embryogenesis

Inter-chromosomal interactions play a crucial role in 3D genome organization, yet the organizational principles and functional significances remain elusive. In general, long non-coding RNA (lncRNA) loci and transcripts are frequently associated with transcriptional programs modulated by long-range chromatin interactions. Here, we identified a novel lncRNA named Gm26793, which is abundantly distributed in the primitive streak and mesodermal cells of E7.5 mouse gastrula. Through genetic ablation of Gm26793, we observed a preferential responsiveness to primitive endoderm lineage during stem cell differentiation, as well as enhanced occurrence of transient and degenerative state cells in early mouse embryos when the cell fate segregates between epiblast and primitive endoderm. Mechanistically, we revealed the genomic locus of Gm26793, rather than the lncRNA transcript or adjacent gene governs the cell fate preference towards primitive endoderm. Concretely, Gm26793 locus (Chr 7) forms an inter-chromosomal molecular lock with Cubn (Chr 2), restraining the expression of Cubn and maintaining a natural epigenetic landscape, thus ensuring the proper lineage specification in vitro and in vivo. In order to reinforce this lock, CTCF and cohesin complex serves as a ring to fasten the inter-chromosomal contact. Overall, our study provides a clear paradigm that inter-chromosomal interaction collaborates with architectural factors to stabilize nuclear conformation and guarantee faithful gene expression during stem cell differentiation and mammalian embryogenesis.

developmental biology↗

Exploration of an enzyme-product mapping approach for plant-derived diterpene synthases

Plant-derived diterpene synthases (PdiTPSs) play a critical role in the formation of structurally and functionally diverse diterpenoids. However, the relationship between PdiTPSs and the specificity or promiscuity of their products remains unclear. To explore this correlation, the sequences of 199 functionally characterized PdiTPSs and their corresponding 3D structures were collected and manually corrected. Using this compiled annotated database, the correlations among PdiTPSs sequences, domains, structures and their corresponding products were comprehensively analyzed. However, utilizing sequence similarity network (SSN), phylogenetic trees, and structural topology features alone was insufficient for effective functional classification of PdiTPSs as these methods could not establish a clear mapping between the enzymes and products. Surprisingly, residues verified to play a function through mutagenesis experiments were located within 8[A] of the substrate. Aromatic residues surrounding the substrate exhibited selectivity towards its chemical structure. Specifically, tryptophan (W) was preferentially located around the linear substrate geranylgeranyl pyrophosphate (GGPP), while phenylalanine (F) and tyrosine (Y) were preferentially located around the initial cyclized diterpene intermediate. This analysis revealed the functional space of residues surrounding the substrate of PdiTPSs, most of which have not been experimentally explored. These findings provide guidance for screening specific residues for mutation studies to change the catalytic products of PdiTPSs, allowing us to better understand the correlation between PdiTPSs and their products.

plant biology↗

A Cellular Platform for Production of C4 Monomers

Living organisms carry out a wide range of remarkable functions, including the synthesis of thousands of simple and complex chemical structures for cellular growth and maintenance. The manipulation of this reaction network has allowed for the genetic engineering of cells for targeted chemical synthesis, but it remains challenging to alter the program underlying their fundamental chemical behavior. By taking advantage of the unique ability of living systems to use evolution to find solutions to complex problems, we have achieved ~95% theoretical yield of three C4 commodity chemicals, n-butanol, 1,3-butanediol, and 4-hydroxy-2-butanone. Genomic sequencing of the evolved strains identified pcnB and rpoBC as two gene loci that are able to alter carbon flow by remodeling the transcriptional landscape of the cell, highlighting the potential of synthetic pathways as a tool to identify metabolic control points.

synthetic biology↗

Self-regulation of PIN1-driven auxin transport by cell surface-based auxin signaling in Arabidopsis

PIN-FORMED (PIN)-driven auxin transport contributes to establishing and maintaining a dynamic auxin concentration gradient alongside plant tissues, which drives the majority of developmental processes in plants. To maintain developmental plasticity in ever-changing environments, plants have evolved self-organizing feedback machinery between auxin signaling and its transport, which has been shown to play essential roles in many fundamental plant processes. However, the molecular mechanism behind this mutual regulation has not yet been clarified. Here, we identified a cell surface-triggered auxin signaling that regulates the PIN1-mediated auxin efflux and further developmental patterning in Arabidopsis. Auxin was able to stimulate PIN1 phosphorylation in plants through transmembrane kinases (TMKs), key components in auxin signaling, at the plasma membrane. TMK1 and TMK4 directly interacted with and phosphorylated PIN1 and functioned redundantly in the regulation of PIN1 polarity in plant cells. The phosphorylation sites in PIN1 proteins, targeted by both auxin and TMKs, were required for PIN1 trafficking and polarity, which further controlled auxin responses and downstream developmental patterning in Arabidopsis. Therefore, our findings provide a direct mechanism for the self-regulation between auxin signaling and transport that drives the auxin flows and proper development in plants.

plant biology↗

Genome structures resolve the early diversification of teleost fishes

Accurate species phylogenies are a prerequisite for evolutionary research. Teleosts are by far the largest and the most diversified group of extant vertebrates, but relationships among the three oldest lineages of extant teleosts remain unresolved. Based on seven high-quality new genome assemblies in Elopomorpha (tarpons, eels), we revisited the topology of the deepest branches of the teleost phylogeny using independent gene sequence and chromosomal rearrangement phylogenomic approaches. These analyses converged to a single scenario that unambiguously places the Elopomorpha and Osteoglossomorpha (bony-tongues) in a monophyletic group sister to all other teleosts, i.e., the Clupeocephala lineage. This finding resolves over 50 years of controversy on the evolutionary relationships of these lineages and highlights the power of combining different levels of genome-wide information to solve complex phylogenies. One-Sentence SummaryWhole-genome analyses place Elopomorpha (tarpons, eels) and Osteoglossomorpha (bony-tongues) as sister groups at the deepest branching of crown teleosts.

evolutionary biology↗

An ancient truncated duplication of the anti-Mullerian hormone receptor type 2 gene is a potential conserved master sex determinant in the Pangasiidae catfish family

The evolution of sex determination (SD) mechanisms in teleost fishes is amazingly dynamic, as reflected by the variety of different master sex-determining genes identified, even sometimes among closely related species. Pangasiids are a group of economically important catfishes in many South-Asian countries, but little is known about their sex determination system. Here, we generated novel genomic resources for 12 Pangasiid species and provided a first characterization of their SD system. Based on an Oxford Nanopore long-read chromosome-scale high quality genome assembly of the striped catfish Pangasianodon hypophthalmus, we identified a duplication of the anti-Mullerian hormone receptor type II gene (amhr2), which was further characterized as being sex-linked in males and expressed only in testicular samples. These first results point to a male-specific duplication on the Y chromosome (amhr2by) of the autosomal amhr2a. Sequence annotation revealed that the P. hypophthalmus Amhr2by is truncated in its N-terminal domain, lacking the cysteine-rich extracellular part of the receptor that is crucial for ligand binding, suggesting a potential route for its neofunctionalization. Short-read genome sequencing and reference-guided assembly of 11 additional Pangasiid species, along with sex-linkage studies, revealed that this truncated amhr2by duplication is also conserved as a male-specific gene in many Pangasiids. Reconstructions of the amhr2 phylogeny suggested that amhr2by arose from an ancient duplication / insertion event at the root of the Siluroidei radiation that is dated around 100 million years ago. Altogether these results bring multiple lines of evidence supporting that amhr2by is an ancient and conserved master sex-determining gene in Pangasiid catfishes, a finding that highlights the recurrent usage of the transforming growth factor {beta} pathway in teleost sex determination and brings another empirical case towards the understanding of the dynamics or stability of sex determination systems.

genomics↗

Large-scale field phenotyping using backpack LiDAR and GUI-based CropQuant-3D to measure structural responses to different nitrogen treatments in wheat

Plant phenomics is widely recognised as a key area to bridge the gap between traits of agricultural importance and genomic information. A wide range of field-based phenotyping solutions have been developed, from aerial-based to ground-based fixed gantry platforms and handheld devices. Nevertheless, several disadvantages of these current systems have been identified by the research community concerning mobility, affordability, throughput, accuracy, scalability, as well as the ability to analyse big data collected. Here, we present a novel phenotyping solution that combines a commercial backpack LiDAR device and our graphical user interface (GUI) based software called CropQuant-3D, which has been applied to phenotyping of wheat and associated 3D trait analysis. To our knowledge, this is the first use of backpack LiDAR for field-based plant research, which can acquire millions of 3D points to represent spatial features of crops. A key feature of the innovation is the GUI software that can extract plot-based traits from large, complex point clouds with limited computing time and power. We describe how we combined backpack LiDAR and CropQuant-3D to accurately quantify crop height and complex 3D traits such as variation in canopy structure, which was not possible to measure through other approaches. Also, we demonstrate the methodological advance and biological relevance of our work in a case study that examines the response of wheat varieties to three different levels of nitrogen fertilisation in field experiments. The results indicate that the combined solution can differentiate significant genotype and treatment effects on key morphological traits, with strong correlations with conventional manual measurements. Hence, we believe that the combined solution presented here could consistently quantify key traits at a larger scale and more quickly than heretofore possible, indicating the system could be used as a reliable research tool in large-scale and multi-location field phenotyping for crop research and breeding activities. We exhibit the systems capability in addressing challenges in mobility, throughput, and scalability, contributing to the resolution of the phenotyping bottleneck. Furthermore, with the fast maturity of LiDAR technologies, technical advances in image analysis, and open software solutions, it is likely that the solution presented here has the potential for further development in accuracy and affordability, helping us fully exploit available genomic resources.

bioinformatics↗

Amphipathic Bax core dimer forms part of apoptotic pore wall in the mitochondrial membrane

Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. They may embed in the cytosolic leaflet of the lipid bilayer generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, they may comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determine a high-resolution structure of the Bax core region that forms a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but creating polar interactions between charged residues and lipid heads. Structure-guided mutations demonstrate the importance of both protein-lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.

biophysics↗

RADSex: a computational workflow to study sex determination using Restriction Site-Associated DNA Sequencing data

The study of sex determination and sex chromosome organisation in non-model species has long been technically challenging, but new sequencing methodologies are now enabling precise and high-throughput identification of sex-specific genomic sequences. In particular, Restriction Site-Associated DNA Sequencing (RAD-Seq) is being extensively applied to explore sex determination systems in many plant and animal species. However, software designed to specifically search for sex-biased markers using RAD-Seq data is lacking. Here, we present RADSex, a computational analysis workflow designed to study the genetic basis of sex determination using RAD-Seq data. RADSex is simple to use, requires few computational resources, makes no prior assumptions about type of sex-determination system or structure of the sex locus, and offers convenient visualization through a dedicated R package. To demonstrate the functionality of RADSex, we re-analyzed a published dataset of Japanese medaka, Oryzias latipes, where we uncovered a previously unknown Y chromosome polymorphism. We then used RADSex to analyze new RAD-Seq datasets from 15 fish species spanning multiple systematic orders. We identified the sex determination system and sex-specific markers in six of these species, five of which had no known sex-markers prior to this study. We show that RADSex greatly facilitates the study of sex determination systems in non-model species and outperforms the commonly used RAD-Seq analysis software STACKS. RADSex in speed, resource usage, ease of application, and visualization options. Furthermore, our analysis of new datasets from 15 species provides new insights on sex determination in fish.

bioinformatics↗

Sex chromosome and sex locus characterization in the goldfish, Carassius auratus

BackgroundGoldfish is an important model for various areas of research, including neural development and behavior and a species of significant importance in aquaculture, especially as an ornamental species. It has a male heterogametic (XX/XY) sex determination system that relies on both genetic and environmental factors, with high temperatures being able to produce female-to-male sex reversal. Little, however, is currently known on the molecular basis of genetic sex determination in this important cyprinid model. We used sequencing approaches to better characterize sex determination and sex-chromosomes in goldfish. ResultsOur results confirmed that sex determination in goldfish is a mix of environmental and genetic factors and that its sex determination system is male heterogametic (XX/XY). Using reduced representation (RAD-seq) and whole genome (pool-seq) approaches, we characterized sex-linked polymorphisms and developed male specific genetic markers. These male specific markers were used to distinguish sex-reversed XX neomales from XY males and to demonstrate that XX female-to-male sex reversal could even occur at a relatively low rearing temperature (18{degrees}C), for which sex reversal has been previously shown to be close to zero. We also characterized a relatively large non-recombining region ([~]11.7 Mb) on goldfish linkage group 22 (LG22) that contained a high-density of male-biased genetic polymorphisms. This large LG22 region harbors 373 genes, including a single candidate as a potential master sex gene, i.e., the anti-Mullerian hormone gene (amh). However, no sex-linked polymorphisms were detected in the goldfish amh gene or its 5 kb proximal promoter sequence. ConclusionsThese results show that goldfish have a relatively large sex locus on LG22, which is likely the goldfish Y chromosome. The presence of a few XX males even at low temperature also suggests that other environmental factors in addition to temperature could trigger female-to-male sex reversal. Finally, we also developed sex-linked genetic markers in goldfish, which will be important for future research on sex determination and aquaculture applications in this species.

genomics↗

Structural characterization of the N-terminal domain of the Dictyostelium discoideum mitochondrial calcium uniporter

The mitochondrial calcium uniporter (MCU) plays a critical role in the mitochondrial calcium uptake into the matrix. In metazoans, the uniporter is a tightly regulated multi-component system including the pore-forming subunit MCU and several regulators (MICU1, MICU2, EMRE). The calcium-conducting activity of metazoan MCU requires the single-transmembrane protein EMRE. Dictyostelium discoideum (Dd), however, developed a simplified uniporter for which the pore-forming MCU (DdMCU) alone is necessary and sufficient for calcium influx. Here, we report a crystal structure of the N-terminal domain (NTD) of DdMCU at 1.7 [A] resolution. The DdMCU-NTD contains four helices and two strands arranged in a fold that is completely different from the known structures of other MCU-NTD homologs. Biochemical and biophysical analyses of DdMCU-NTD in solution indicated that the domain exists as oligomers, most probably as a pentamer or hexamer. Mutagenesis showed that the acidic residues Asp60, Glu72 and Glu74, which appeared to mediate the parallel interface as observed in the crystal structure, participated in the self-assembly of DdMCU-NTD. Intriguingly, the oligomeric complex readily dissociated to lower-order oligomers in the presence of calcium. We propose that the calcium-triggered dissociation of NTD regulates the channel activity of DdMCU by a yet unknown mechanism.

biophysics↗

Characterization of a Y-specific duplication/insertion of the anti-Mullerian hormone type II receptor gene based on a chromosome-scale genome assembly of yellow perch, Perca flavescens

BackgroundYellow perch, Perca flavescens, is an ecologically and commercially important species native to a large portion of the northern United States and southern Canada. It is also a promising candidate species for aquaculture. No yellow perch reference genome, however, has been available to facilitate improvements in both fisheries and aquaculture management practices.\n\nFindingsBy combining Oxford Nanopore Technologies long-reads, 10X genomics Illumina short linked reads and a chromosome contact map produced with Hi-C, we generated a high-continuity chromosome scale yellow perch genome assembly of 877.4 Mb. It contains, in agreement with the known diploid chromosome yellow perch count, 24 chromosome-size scaffolds covering 98.8% of the complete assembly (N50 = 37.4 Mb, L50 = 11). Genome annotation identified 41.7% (366 Mb) of repeated elements and 24,486 genes including 16,579 genes (76.3%) significantly matching with proteins in public databases. We also provide a first characterization of the yellow perch sex determination locus that contains a male-specific duplicate of the anti-Mullerian hormone type II receptor gene (amhr2by) inserted at the proximal end of the Y chromosome (chromosome 9). Using this sex-specific information, we developed a simple PCR genotyping test which accurately differentiates XY genetic males (amhr2by+) from XX genetic females (amhr2by-).\n\nConclusionsOur high-quality genome assembly is an important genomic resource for future studies on yellow perch ecology, toxicology, fisheries, and aquaculture research. In addition, the characterization of the amhr2by gene as a candidate sex determining gene in yellow perch provides a new example of the recurrent implication of the transforming growth factor beta pathway in fish sex determination, and highlights gene duplication as an important genomic mechanism for the emergence of new master sex determination genes.

genomics↗