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PubMed2025

Genetic effect of the Ph1 locus on transcriptome atlas of anther development-related genes, meiotic chromosome behavior and agronomic traits in bread wheat.

Proper spatiotemporal expression of meiosis-related genes (MRGs) and other male-microsporogenesis/microgametogenesis-related genes (MMRGs) is crucial for normal anther development, yet their expression patterns remain largely unknown in wheat. The Ph1 locus in wheat is known to contain the Ph1 gene that plays a dual role in promoting pairing between homologous chromosomes but repressing pairing between homoeologous chromosomes, but its genetic function is still unclear. Here, we investigated these issues by conducting a comprehensive transcriptome analysis during wheat anther development in Chinese Spring (CS) and its ph1b deletion mutant under greenhouse and field conditions. Our results revealed that MRGs and MMRGs are predominantly expressed during pre-meiosis stages, with MMRGs also being highly expressed in meiotic-II. Gene co-expression analysis showed that C2H2 and B3 transcriptional factors (TFs) are associated with MRGs, and MYB regulators interacted mainly with MMRGs during microgametogenesis. Deletion of genes within the Ph1 locus failed to induce compensatory transcriptional activation of their homoeologous counterparts, while genes outside the Ph1 locus showed environmental-specific responses, especially during meiotic-II and mature pollen stages. Notably, early disjunction of bivalent chromosomes is a primary factor leading to defective meiocytes during metaphase I. Furthermore, the ph1b deletion mutant exhibited a substantially delayed heading date, potentially contributing to environment-stable and environment-specific alterations in fertility and grain-related traits. Our study highlights the significant impact of the Ph1 locus on the transcriptome during anther development, and a previously unheeded effect on meiotic chromosome pairing and agronomic traits, suggesting potential for genetic manipulations within the Ph1 locus for wheat improvement.

Triticum↗
PubMed2026

Genomic introgressions from wild relatives in the wheat genome alter meiotic dynamics in inter-varietal hybrids.

The use of wild relatives to introduce original diversity in the genome of bread wheat (Triticum aestivum L.) is an interesting approach to face the challenges of sustainable agriculture and the impact of climate change on wheat production. However, the influence of these wild-species introgressions on meiosis in inter-varietal wheat hybrids remains poorly understood. We analyzed the French wheat variety Renan (Re) carrying Aegilops ventricosa (Aev)-derived 2AS/2NS and 7DL/7DvL introgressions, the reference cultivar Chinese Spring (CS), which lacks these introgressions, and their inter-varietal hybrid Chinese Spring × Renan (CSRe). This analysis combined cytogenetic approaches with the assessment of reproductive performance. Furthermore, we generated a cytological atlas of meiosis in wild tetraploid Aev, quantifying bivalent configurations and chiasma frequency. We observed a reduced pollen viability and a slight decrease in floret fertility in the hybrid CSRe. Exploration of the meiotic behavior showed that CSRe exhibited increased numbers of rod bivalents and univalents, leading to a reduced average chiasma number and frequent chromosome bridges and fragmentations, whereas the parental lines maintained stable chromosome pairing. These rearrangements indicate that homologous chromosome pairing and recombination are affected in CSRe. We applied introgression-specific oligo-Fluorescent In Situ Hybridization to localize alien segments in CSRe, providing a novel strategy to investigate the meiotic behavior of introgressed regions. The 2AS/2NS introgressed segments in CSRe were frequently located on rod bivalents or univalents, while 7DL/7DvL segments consistently formed ring bivalents. Our results provide a foundation for guiding alien gene introgression and for understanding the behavior of chromosomes with introgressions in the wheat genome.

Meiosis↗
PubMed2026

Supergene control of chiral development in mirror-image flowers.

How genes determine the development of chiral structures is a fascinating question. The reciprocal placement of female and male organs on opposite sides of mirror-image flowers promotes efficient cross-pollination. Here, we identified that in butterfly lilies, female and male organs deflect by a combination of genetically controlled chirality and gravitropism, orienting left and right with respect to an external rather than internal reference axis. We found coordinated organ placement to be controlled by a hemizygous supergene containing two candidate causal loci, MIR156-R and YUCCA-R, that are responsible for opposite female and male organ orientation, respectively. The resulting differential placement of pollen carrying the two supergene alleles on pollinators' bodies leads to their transfer to the stigmas of flowers with opposite handedness and maintenance of the reproductive polymorphism.

Alleles↗
PubMed2026

Feeding the disease: The impact of nutritional supplementation on Nosema (Vairimorpha) infection in honey bees (Apis mellifera).

Honey bees (Apis mellifera) experience variable colony losses across regions and years, with infectious diseases representing a key component of colony health challenges. Among the most prevalent pathogens are the microsporidian parasites Nosema apis and Nosema ceranae, whose impacts on host survival and transmission vary widely depending on context. While nutritional supplementation is commonly used to support honey bee health, its effects on Nosema infection outcomes remain unclear. Here, we experimentally tested whether dietary enrichment alters survival and infection intensity following exposure to a mixed Nosema inoculum. Newly emerged worker bees were challenged with Nosema spores and maintained on either a basic sucrose diet or the same diet supplemented with a commercial pollen substitute. Dietary enrichment significantly increased both mortality risk and infection intensity in Nosema-infected bees, while having no detectable effect on survival in uninfected controls. These results indicate that supplementation can, counter intuitively, exacerbate nosemosis by promoting parasite replication rather than enhancing host resistance. Our findings highlight the importance of distinguishing nutritional effects on host tolerance versus resistance, and caution that interventions intended to improve bee nutrition may inadvertently increase pathogen production and transmission potential under certain conditions.

Animals↗
PubMed2026

Denisovans from southwestern China and their subsistence strategies.

Growing fossil and genomic evidence has substantially advanced our understanding of Denisovans' evolutionary history1-9, yet their technological behaviours and subsistence strategies remain poorly documented. Here we present a comprehensive analysis of hominin fossils and associated archaeological remains from Bianfu Cave, Yunnan Province, southwestern China. The hominin fossils are dated to about 167-134 thousand years ago (ka), whereas the cultural sequence spanned from about 190 ka to 70 ka, representing one of the longest cultural records most parsimoniously attributed to Denisovans-identified through enamel-dentine junction morphology and palaeoproteomic analyses10. The new fossils include four teeth that expand the known dental variation of this group, two cranial fragments and a radius. Faunal and pollen records indicate a conifer-dominated forest or forest-steppe environment across Marine Isotope Stages 6 to 4. The inhabitants of Bianfu Cave practised specialized hunting of medium- to large-bodied prey and used a technological strategy characterized by expedient core reduction and tool production, alongside pervasive use of unmodified bones. This pattern suggests an adaptive system prioritizing the exploitation of object affordance over intensive tool manufacture. Bianfu Cave provides unprecedented insights into Denisovan biology, behaviour and ecology in eastern Asia and points to a substantial genetic and cultural legacy in later populations in Southeast Asia and Oceania.

Journal Article↗
PubMed2026

Resolving taxonomic complexity in the genus Boechera (Brassicaceae) using the Boechera Microsatellite Website: a case study of the rare triploid B. bodiensis.

BACKGROUND AND AIMS: The genus Boechera (rock cress) comprises ∼75 sexual diploid taxa and >355 genetically distinct hybrid lineages, many of which reproduce asexually through apomixis. This complex reproductive landscape poses substantial challenges for taxonomy, similar to those encountered in genera such as Taraxacum, Hieracium, Poa and Rubus. The Boechera Microsatellite Website (BMW) offers an extensive database and analytical tools that are proving instrumental in resolving these difficulties. Here, we demonstrate the utility of the BMW through analysis of Boechera bodiensis, a rare and poorly understood species endemic to the western Great Basin of the USA. METHODS: First described as Arabis bodiensis by Rollins in 1982, this taxon is sparsely represented in herbaria and has long been considered a candidate for protection under the Endangered Species Act. However, its taxonomic identity has remained uncertain owing to morphological similarities with other 'Arabis' (Boechera) taxa. We integrate microsatellite DNA data from the BMW with morphological analyses to provide a clearer understanding of the taxonomic status, distribution and evolutionary origins of B. bodiensis. KEY RESULTS: Pollen studies reveal that B. bodiensis is a diplosporous apomict. Microsatellite genotyping of the holotype confirms it to be triploid, containing three subgenomes derived from Boechera cobrensis, B. fernaldiana and B. sparsiflora. Expanded microsatellite surveys detect this triploid genotype at 22 additional sites, primarily in Mono County, CA, USA. Morphological analyses of genetically verified specimens identify a consistent set of characters that distinguish B. bodiensis from co-occurring congeners. CONCLUSIONS: The BMW enables high-resolution analyses of genome composition, reproductive mode and hybrid origins, making it a powerful tool for resolving taxonomic complexity in Boechera. Our case study of B. bodiensis highlights the effectiveness of combining molecular and morphological data to clarify species boundaries, inform conservation assessments and refine nomenclatural understanding in this notoriously difficult genus.

Microsatellite Repeats↗
PubMed2026

A high-quality draft genome assembly of Johnsongrass illuminates relationships between polyploidization, crop-wild hybridization, and reproductive biology.

Johnsongrass [Sorghum halepense (L.) Pers.] is an allopolyploid, rhizomatous, perennial grass species and one of the most troublesome weeds in global agriculture. We assembled the first Johnsongrass genome to clarify poorly understood genetic factors influencing variable rates of crop-wild hybridization with cultivated sorghum [S. bicolor (L.) Moench]. The draft genome assembly has a total size of 3.26 Gb and BUSCO completeness of 95.3%. We also report the first evolutionary analysis of INHIBITION OF ALIEN POLLEN (IAP), the only known cross-(in)compatibility locus in the genus. Our results reveal an evolutionary history of genome instability, including the loss of distinct parental subgenomes, and suggest that Nebraska accession 'J-37,' the genome donor, is a segmental allotetraploid that may function as a diploid or aneuploid during meiosis. Genome instability could explain observations of variable ploidies in Johnsongrass and facilitate ongoing hybridization with sorghum where gamete ploidies and IAP alleles match. Given this information, we provide a suggested research framework for studying evolution and gene expression in the Sorghum genus where crop-wild hybridization occurs and for predicting the potential for hybridization between specific crossing partners. Collectively, this work will bolster efforts to study and manage reproductive biology in other crop-wild polyploid complexes.

Sorghum↗
PubMed2025

PSIA: A Comprehensive Knowledgebase of Plant Self-incompatibility.

Self-incompatibility (SI) is an important genetic mechanism in angiosperms that prevents inbreeding and promotes outcrossing, with significant implications for crop breeding, including genetic diversity, hybrid seed production, and yield optimization. In eudicots, SI is typically governed by a single S-locus containing tightly linked pistil and pollen S-determinant genes. Despite major advances in SI research, a centralized, comprehensive resource for SI-related genomic data remains lacking. To address this gap, we developed the Plant Self-Incompatibility Atlas (PSIA), a systematically curated knowledgebase providing an extensive compilation of plant SI, including genomic resources for SI species, S gene annotations, molecular mechanisms, phylogenetic relationships, and comparative genomic analyses. The current release of PSIA includes over 500 genome assemblies from 469 SI species. Using known S genes as queries, we manually identified and rigorously curated 3700 S genes. PSIA provides detailed S-locus information from assembled genomes of SI species and offers an interactive platform for browsing, BLAST searches, S gene analysis, and data retrieval. Additionally, PSIA serves as a unique platform for comparative genomic studies of S-loci, facilitating exploration of the dynamic processes underlying the origin, loss, and regain of SI. As a comprehensive and user-friendly resource, PSIA will greatly advance our understanding of angiosperm SI and serve as a valuable tool for crop breeding and hybrid seed production. PSIA is freely available at http://www.plantsi.cn.

Self-Incompatibility in Flowering Plants↗
PubMed2025

Sex-dependent influence of LMAN1 on allergen-induced airway hyperresponsiveness.

Allergic asthma is a chronic inflammatory disease of the airways characterized by a type 2-high adaptive immune response towards common aeroantigens such as dust mite, pollen, and animal dander. Despite the advances made toward translation of various biologics into the clinic, the limited efficacy of these therapies in certain populations, combined with the ineligibility of some patients for treatment (clinically or economically), have led to the continued need for the development of more widely effective allergic asthma therapies. Our lab previously identified lectin mannose-binding 1 (LMAN1) as a novel receptor for house dust mite (HDM) and showed that in vitro, LMAN1 downregulated inflammatory NF-κB signaling in DCs in response to HDM. In this follow-up work, we investigated the in vivo relevance of LMAN1 by subjecting LMAN1 knockout (KO) mice and wild type (WT) littermate controls to a model of HDM-induced allergic asthma. Surprisingly, we discovered that loss of LMAN1 led to opposing effects on airway hyperresponsiveness (AHR), which were dependent on the sex of the mice. HDM-treated female LMAN1 KO mice showed increased AHR, while HDM-treated male KO mice showed decreased AHR, compared with their WT counterparts. We further identified the features of HDM-induced asthma which may account for the gender-biased effects of LMAN1 on lung function. This work not only highlights the complexity of the loss of LMAN1 in vivo but also suggests that such sex-dependent responses should be taken into consideration when pursuing LMAN1 as a therapeutic target for treatment of allergic asthma.

Animals↗
PubMed2026

Haplotype-resolved genome of Forsythia suspensa reveals the reticulate evolution in Oleaceae and a novel gene cluster regulating stamen development.

The olive family (Oleaceae) comprises numerous species of economic, horticultural, and medicinal importance. Despite its significance, the evolutionary history of this complex family remains enigmatic. Here, we generated a high-quality haplotype-resolved genome of Forsythia suspensa, a distylous species that occupies a key phylogenetic position in Oleaceae. The 2 haplotypes exhibit significant allelic divergence with potential allele-specific regulation. We reconstructed the polyploidization history of Oleaceae by confirming and precisely dating a shared whole-genome triplication and an independent whole-genome duplication event. We revealed a complex reticulate evolution that gave rise to the tribe Oleeae: an initial hybridization between Forsythieae (♂) and Jasmineae (♀), a subsequent backcrossing event, and a final whole-genome duplication. We identified a novel tandemly duplicated pectin methylesterase inhibitor gene cluster that regulates filament length and pollen size via restricting cell elongation in the long-styled morph. Dosage augmentation via stepwise cluster formation (0.99 to 3.83 Mya) may contribute to maintaining stamen traits of the long-styled morph. These FsPMEIs are co-expressed with many cell wall-related genes, suggesting a functional link in cell wall modification. Our study reveals the reticulate evolution in Oleaceae and a novel gene cluster controlling stamen development in F. suspensa and provides valuable haplotype-resolved genomic resources for heterostylous species, offering novel framework and molecular pathways to understand plant adaptive evolution.

Forsythia↗
PubMed2026

Analyzing Meiosis in Maize.

Meiosis is central to sexual reproduction and the main source of genetic diversity in plants. Understanding how meiotic processes are regulated has direct relevance to agriculture. As meiotic recombination is the vehicle of plant breeding, gaining the ability to influence recombination patterns can accelerate crop improvement. Maize is a powerful model for studying plant meiosis, thanks to its large chromosomes, well-developed genetics, and the availability of diverse cytogenetic and molecular tools. Insights gained from maize studies can extend to other species. In this review, we describe a variety of approaches for examining meiosis and meiotic recombination in maize. Cytological techniques, including protein immunolocalization and fluorescence in situ hybridization (FISH), enable visualization of chromosome structure and behavior, as well as crossover (CO) formation. Chromatin immunoprecipitation (ChIP) is used in meiosis research to determine locations of recombination proteins, identify recombination sites, and elucidate chromatin features, such as histone modifications. Quantification of COs at specific genomic sites through pollen typing by droplet digital PCR allows precise high-resolution measurement of recombination rates. Combining cytology, protein localization, and molecular assays provides a multiscale picture of meiosis, linking molecular mechanisms to chromosome behavior and, ultimately, to genetic variation.

Journal Article↗
PubMed2025

Patterns of Genomic Divergence and Introgression in Two Primulina Hybrid Zones.

Hybrid zones have long been promoted as natural laboratories for understanding the mechanisms of speciation. Multiple or replicated hybrid zones are particularly informative, as they allow for assessing the consistency of genomic divergence and introgression across different environmental contexts and demographic histories, thereby improving our understanding of the factors that drive or hinder speciation on a broader scale. Here, using whole-genome resequencing data, we compare the patterns of genomic divergence and introgression in two Primulina hybrid zones. We found that genomic divergence in both hybrid zones is largely shaped by neutral processes, with only a few genomic regions showing signatures of balancing or lineage-specific selection. Genomic cline analyses identified numerous SNPs that showed significantly steeper clines and biased centres than the genome-wide expectation in both hybrid zones, consistent with the existence of reproductive barriers. Within regions of restricted gene flow, we identified 21 genes shared between the two hybrid zones. Annotation of gene function revealed that several genes are involved in reproductive processes. In addition, many zone-specific outlier loci were linked to genes associated with pollen and flower development, suggesting that these barriers may contribute to reproductive isolation under localised ecological conditions. Overall, these findings suggest that while certain reproductive barriers remain consistent across independent hybrid zones, others may be contingent on local environmental contexts. Our results demonstrate that both general and zone-specific mechanisms contribute to reproductive isolation in Primulina, providing empirical evidence that some genomic barriers recur across independent hybrid zones while others arise through localised adaptation.

Lamiales↗
PubMed2026

The combination of morphogenic regulators BABY BOOM and GRF-GIF improves maize transformation efficiency and promotes leaf regeneration.

Transformation is an indispensable tool for plant genetics and functional genomics. Although stable transformation in maize is no longer a major obstacle, there remains a need for accessible and efficient methods for academic laboratories. Here, we present the GGB system, a rapid and efficient approach optimized for immature embryo transformation in B104 and other maize lines. This system combines two distinct morphogenetic regulators, the wheat GRF4-GIF1 chimera and the maize BABY BOOM (BBM) transcription factor (hence the name "GGB") with a modified QuickCorn protocol, enabling regeneration of transformed maize plantlets in c. 2 months with an efficiency 7-fold higher than when compared to either morphogenic factor used in isolation. Expression of both regulators did not significantly affect development, eliminating the need to excise them after regeneration. However, transmission of the transgenic GGB construct through pollen was significantly reduced, potentially aiding transgenic line containment. We show that the GGB system is adaptable for CRISPR-Cas9 editing and reporter line generation. Furthermore, stable GGB transformants exhibited high leaf regeneration capacity via somatic embryogenesis. RNA-seq time-course profiling of GGB leaf cultures identified additional factors that could promote regeneration and led to the discovery of asparagine and trehalose as additional media components that significantly enhanced leaf regeneration.

Zea mays↗
PubMed2026

Generational variation and stabilization in resynthesized allotetraploid Brassica juncea derived from diploid progenitors B. rapa and B. nigra.

BACKGROUND: Polyploidy is a major driver of plant evolution and crop improvement, generating novel variation in morphology, physiology, and agronomic traits. Brassica juncea (AABB, 2n = 36), a natural allotetraploid derived from B. rapa (AA) and B. nigra (BB), is an important oilseed and vegetable crop; however, its narrow genetic base limits further breeding gains. Resynthesized B. juncea (RBJ), developed from known progenitors, provides a tractable system to investigate polyploid stabilization, trait diversification, and generational variation. This study evaluated RBJ across nine generations (F1-S8) to elucidate generational variation in morphological, molecular, cytological, and oil content traits during progressive stabilization. RESULTS: Substantial variation was observed for key yield-related traits, including siliqua length, seeds per siliqua, and thousand-seed weight. High estimates of heritability, genotypic variance, and genetic advance indicated their potential utility in selection based improvement. Comparative analyses revealed a clear generational progression, characterized by relatively enhanced performance in early generations, increased recombination-driven variability in intermediate generations, and the partial stabilization of several traits in later generations. Generation mean analysis suggested the involvement of additive, dominance, and epistatic gene effects in trait inheritance. Molecular analysis using SSR markers confirmed the amphidiploid origin and genomic integrity of RBJ generations. Cytological assessments, pollen viability assays, and flow cytometric analysis collectively demonstrated stable chromosome numbers, improved fertility, and maintenance of ploidy stability across successive generations. CONCLUSIONS: The study provides valuable insights into the generational variation and stabilization of morphological, molecular, and oil content traits in resynthesized B. juncea. The findings suggest that variability arising from polyploidization and interspecific hybridization undergoes gradual reorganization across successive generations, leading to increased trait stabilization and more consistent expression of selected agronomic characteristics. Collectively, these results contribute to the understanding of early stabilization processes in RBJ, highlighting resynthesized polyploids as useful systems for studying variation and stabilization in allopolyploid crops.

Mustard Plant↗
PubMed2026

Evaluating three alternative scenarios for the origin of a disjunct Arctium tomentosum population in the Pyrenees.

BACKGROUND: Disjunctions in species distributions offer natural experiments for investigating the mechanisms underlying distributional breaks, such as range contraction, long-distance pollen transport, or long-distance seed dispersal. Here, we document and characterise a floristic novelty in the Pyrenean and Iberian regions, and use it as a case study to investigate the processes underlying disjunct species distributions. Our analysis focuses on Arctium L. (burdocks), a genus native to Eurasia comprising several cosmopolitan weedy species. It is characterised by hooked capitula that facilitate epizoochorous dispersal. METHODS: To clarify the taxonomic identity of a previously undocumented Pyrenean population resembling A. tomentosum, we adopted an integrative approach, combining distribution information, morphology, genome size, repetitive DNA analysis and chloroplast data across the four known European species. Additionally, we conducted a comparative study of functional capitulum traits, predispersal fruit predation, and associated entomofauna for the newly discovered population and nearby A. minus populations. RESULTS: The discovered population constitutes a floristic novelty for the region and is identified as A. tomentosum, exhibiting signatures of past introgression from A. minus, as indicated by cytonuclear discordance. We evaluated three alternative scenarios to explain its origin: (i) persistence as a relict from a previously wider distribution, (ii) long-distance pollination by migrating insects, and (iii) long-distance seed dispersal from an A. tomentosum population with a history of past introgression. Of these, only the third is consistent with the available evidence. These results highlight the complexity of interpreting disjunct species distributions and underscore the value of integrative approaches for resolving population identity, origin, dispersal, and persistence across environments.

Arctium↗
PubMed2026

Alternatively spliced killer-protector system confers S19-mediated hybrid male sterility in rice.

Hybrid sterility limits the use of strong interspecific heterosis and S19 is a major locus that confers hybrid sterility between Oryza sativa (Asian cultivated rice) and Oryza glaberrima (African cultivated rice). However, the S19 is not yet cloned and its underlying mechanism remains elusive. In this study, we identify two closely linked genes (S19A1 and S19A7) specific to African rice allele that encode a killer-protector module at the S19 locus. Two alternatively spliced transcripts expressed from the killer gene S19A1 (S19A1.1 and S19A1.2) encode mitochondria-targeted cytotoxic proteins that cause toxicity diversity for somatic and/or gametic cell death, respectively. However, S19A7 interacts with S19A1.1 and S19A1.2, blocking their cytotoxic effect. Because the Asian rice S19 allele lacks S19A1 and S19A7, male gametes that carry this allele are selectively aborted in Asian-African F1 hybrids. Knockout of S19A1 can overcome S19-mediated hybrid sterility. Haplotype analysis reveals that the functional S19 allele is absent in non-AA-genome Oryza species and likely emerged in the O. barthii-O. glaberrima lineage through a multi-step evolutionary process. Our findings provide insight into the genetic mechanisms responsible for hybrid sterility between Asian and African rice and suggest genetic and biotechnological strategies for the use of interspecific heterosis in rice.

Oryza↗
PubMed2025

The new frontier in understanding human and mammalian brain development.

Neurodevelopmental disorders that cause cognitive, behavioural or motor impairments affect around 15% of children and adolescents worldwide1, with diagnoses of profound autism and attention deficit hyperactivity disorder increasing in the USA and contributing to a major economic burden2,3. Yet the origins and mechanisms of these conditions remain poorly understood, limiting progress in therapies. Comprehensive cell atlases of the developing human brain, alongside those of model organisms such as mice and non-human primates, are now providing high-resolution measures of gene expression, cell-type abundance and spatial distribution. In this Perspective, we highlight recent studies that have identified novel developmental cell populations, revealed conserved and divergent patterns of cell genesis, migration and maturation across species, and begun testing hypotheses that link them to processes ranging from transcriptional control of cell fate specification to the emergence of complex behaviours. We present remaining conceptual and technical challenges and provide an outlook on how further studies of human and mammalian brain development can empower a deeper understanding of neurodevelopmental and neuropsychiatric disorders. Future efforts expanding to additional developmental stages, including adolescence, as well as whole-brain, multimodal and cross-species integration, will yield new insights into how development shapes the brain. These atlases promise to serve as essential references for unravelling mechanisms of brain function and disease vulnerability, and for advancing precision medicine.

Humans↗
PubMed2025

Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.

The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release. We identify human-specific gene expression changes related to axonal transport of mitochondria and reactive oxygen species buffering and candidate cis- and trans-regulatory mechanisms underlying gene expression divergence. Our findings are consistent with a model of evolved neuroprotection in response to tradeoffs related to brain expansion and could contribute to the discovery of therapeutic targets and strategies for treating disorders involving the dopaminergic system.

Brain evolution↗