Current BiologyPub Date : 2025-01-06Epub Date: 2024-12-04DOI: 10.1016/j.cub.2024.10.069
Stephanie N Caty, Aurora Alvarez-Buylla, Cooper Vasek, Elicio E Tapia, Nora A Martin, Theresa McLaughlin, Chloe L Golde, Peter K Weber, Xavier Mayali, Luis A Coloma, Megan M Morris, Lauren A O'Connell
{"title":"Alkaloids are associated with increased microbial diversity and metabolic function in poison frogs.","authors":"Stephanie N Caty, Aurora Alvarez-Buylla, Cooper Vasek, Elicio E Tapia, Nora A Martin, Theresa McLaughlin, Chloe L Golde, Peter K Weber, Xavier Mayali, Luis A Coloma, Megan M Morris, Lauren A O'Connell","doi":"10.1016/j.cub.2024.10.069","DOIUrl":"10.1016/j.cub.2024.10.069","url":null,"abstract":"<p><p>Shifts in host-associated microbiomes can impact both host and microbes.<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>4</sup><sup>,</sup><sup>5</sup><sup>,</sup><sup>6</sup> It is of interest to understand how perturbations, like the introduction of exogenous chemicals,<sup>7</sup><sup>,</sup><sup>8</sup><sup>,</sup><sup>9</sup><sup>,</sup><sup>10</sup><sup>,</sup><sup>11</sup><sup>,</sup><sup>12</sup><sup>,</sup><sup>13</sup> impact microbiomes. In poison frogs (family Dendrobatidae), the skin microbiome is exposed to alkaloids that the frogs sequester for defense.<sup>14</sup><sup>,</sup><sup>15</sup><sup>,</sup><sup>16</sup><sup>,</sup><sup>17</sup><sup>,</sup><sup>18</sup><sup>,</sup><sup>19</sup> These alkaloids are antimicrobial<sup>20</sup><sup>,</sup><sup>21</sup><sup>,</sup><sup>22</sup>; however, their effect on the frogs' skin microbiome is unknown. To test this, we characterized microbial communities from field-collected dendrobatid frogs. Then, we conducted a laboratory experiment to monitor the effect of the alkaloid decahydroquinoline (DHQ) on the microbiome of two frog species with contrasting alkaloid loads in nature. In both datasets, we found that alkaloid-exposed microbiomes were more phylogenetically diverse, with an increase in diversity among rare taxa. To better understand the isolate-specific response to alkaloids, we cultured microbial isolates from poison frog skin and found that many isolates exhibited enhanced growth or were not impacted by the addition of DHQ. To further explore the microbial response to alkaloids, we sequenced the metagenomes from high- and low-alkaloid frogs and observed a greater diversity of genes associated with nitrogen and carbon metabolism in high-alkaloid frogs. From these data, we hypothesized that some strains may metabolize the alkaloids. We used stable isotope tracing coupled to nanoSIMS (nanoscale secondary ion mass spectrometry), which supported the idea that some of these isolates are able to metabolize DHQ. Together, these data suggest that poison frog alkaloids open new niches for skin-associated microbes with specific adaptations, such as alkaloid metabolism, that enable survival in this environment.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"187-197.e8"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06Epub Date: 2024-12-05DOI: 10.1016/j.cub.2024.10.075
Guifré Torruella, Luis Javier Galindo, David Moreira, Purificación López-García
{"title":"Phylogenomics of neglected flagellated protists supports a revised eukaryotic tree of life.","authors":"Guifré Torruella, Luis Javier Galindo, David Moreira, Purificación López-García","doi":"10.1016/j.cub.2024.10.075","DOIUrl":"10.1016/j.cub.2024.10.075","url":null,"abstract":"<p><p>Eukaryotes evolved from prokaryotic predecessors in the early Proterozoic<sup>1</sup><sup>,</sup><sup>2</sup> and radiated from their already complex last common ancestor,<sup>3</sup> diversifying into several supergroups with unresolved deep evolutionary connections.<sup>4</sup> They evolved extremely diverse lifestyles, playing crucial roles in the carbon cycle.<sup>5</sup><sup>,</sup><sup>6</sup> Heterotrophic flagellates are arguably the most diverse eukaryotes<sup>4</sup><sup>,</sup><sup>7</sup><sup>,</sup><sup>8</sup><sup>,</sup><sup>9</sup> and often occupy basal positions in phylogenetic trees. However, many of them remain undersampled<sup>4</sup><sup>,</sup><sup>10</sup> and/or incertae sedis.<sup>4</sup><sup>,</sup><sup>11</sup><sup>,</sup><sup>12</sup><sup>,</sup><sup>13</sup><sup>,</sup><sup>14</sup><sup>,</sup><sup>15</sup><sup>,</sup><sup>16</sup><sup>,</sup><sup>17</sup><sup>,</sup><sup>18</sup> Progressive improvement of phylogenomic methods and a wider protist sampling have reshaped and consolidated major clades in the eukaryotic tree.<sup>13</sup><sup>,</sup><sup>14</sup><sup>,</sup><sup>15</sup><sup>,</sup><sup>16</sup><sup>,</sup><sup>17</sup><sup>,</sup><sup>18</sup><sup>,</sup><sup>19</sup> This is illustrated by the Opimoda,<sup>14</sup> one of the largest eukaryotic supergroups (Amoebozoa, Ancyromonadida, Apusomonadida, Breviatea, CRuMs [Collodictyon-Rigifila-Mantamonas], Malawimonadida, and Opisthokonta-including animals and fungi).<sup>4</sup><sup>,</sup><sup>14</sup><sup>,</sup><sup>19</sup><sup>,</sup><sup>20</sup><sup>,</sup><sup>21</sup><sup>,</sup><sup>22</sup> However, their deepest evolutionary relationships still remain uncertain. Here, we sequenced transcriptomes of poorly studied flagellates<sup>23</sup><sup>,</sup><sup>24</sup> (14 apusomonads,<sup>25</sup><sup>,</sup><sup>26</sup> 7 ancyromonads,<sup>27</sup> and 1 cultured Mediterranean strain of Meteora sporadica<sup>17</sup>) and conducted comprehensive phylogenomics analyses with an expanded taxon sampling of early-branching protists. Our findings support the monophyly of Opimoda, with CRuMs being sister to the Amorphea (amoebozoans, breviates, apusomonads, and opisthokonts) and ancyromonads and malawimonads forming a moderately supported clade. By mapping key complex phenotypic traits onto this phylogenetic framework, we infer an opimodan biflagellate ancestor with an excavate-like feeding groove, which ancyromonads subsequently lost. Although breviates and apusomonads retained the ancestral biflagellate state, some early-diverging Amorphea lost one or both flagella, facilitating the evolution of amoeboid morphologies, novel feeding modes, and palintomic cell division resulting in multinucleated cells. These innovations likely facilitated the subsequent evolution of fungal and metazoan multicellularity.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"198-207.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06Epub Date: 2024-12-02DOI: 10.1016/j.cub.2024.11.006
Shaun F Morrison, Georgina Cano, Shelby L Hernan, Pierfrancesco Chiavetta, Domenico Tupone
{"title":"Inhibition of the hypothalamic ventromedial periventricular area activates a dynorphin pathway-dependent thermoregulatory inversion in rats.","authors":"Shaun F Morrison, Georgina Cano, Shelby L Hernan, Pierfrancesco Chiavetta, Domenico Tupone","doi":"10.1016/j.cub.2024.11.006","DOIUrl":"10.1016/j.cub.2024.11.006","url":null,"abstract":"<p><p>To maintain core body temperature in mammals, CNS thermoregulatory networks respond to cold exposure by increasing brown adipose tissue and shivering thermogenesis. However, in hibernation or torpor, this canonical thermoregulatory response is replaced by a new, emerging paradigm, thermoregulatory inversion (TI), an alternative homeostatic state in which cold exposure inhibits thermogenesis and warm exposure stimulates thermogenesis. Here, we demonstrate that in the non-torpid rat, either exclusion of the canonical thermoregulatory integrator in the preoptic hypothalamus or inhibition of neurons in the ventromedial periventricular area (VMPeA) induces the TI state through an alternative thermoregulatory pathway. Within this pathway, we have identified a dynorphinergic input to the dorsomedial hypothalamus from the dorsolateral parabrachial nucleus that plays a critical role in mediating the cold-evoked inhibition of thermogenesis during TI. Our results reveal a novel thermosensory reflex circuit within the mammalian CNS thermoregulatory pathways and support the potential for pharmacologically inducing the TI state to elicit therapeutic hypothermia in non-hibernating species, including humans.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"59-76.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A language model of problem solving in humans and macaque monkeys.","authors":"Qianli Yang, Zhihua Zhu, Ruoguang Si, Yunwei Li, Jiaxiang Zhang, Tianming Yang","doi":"10.1016/j.cub.2024.10.074","DOIUrl":"10.1016/j.cub.2024.10.074","url":null,"abstract":"<p><p>Human intelligence is characterized by the remarkable ability to solve complex problems by planning a sequence of actions that takes us from an initial state to a desired goal state. Quantifying and comparing problem-solving capabilities across species and finding their evolutionary roots are critical for understanding how the brain carries out this intricate process. We introduce the Language of Problem Solving (LoPS) model as a novel quantitative framework that investigates the structure of problem-solving behavior through a language model. We applied the model to an adapted classic Pac-Man game as a cross-species behavioral paradigm to test both humans and macaque monkeys. The LoPS model extracted the latent structure, or grammar, embedded in the agents' gameplay, revealing the non-Markovian temporal dependency structure of their problem-solving behavior and the hierarchical structures of problem solving in both species. The complexity of LoPS grammar correlated with individuals' game performance and reflected the difference in problem-solving capacity between humans and monkeys. Both species evolved their LoPS grammars during learning, progressing from simpler to more complex ones, suggesting that the structure of problem solving is not fixed but evolves to support more sophisticated and efficient problem solving. Our study provides insights into how humans and monkeys break down problem solving into compositional units and navigate complex tasks, deepening our understanding of human intelligence and its evolution and establishing a foundation for future investigations of the neural mechanisms of problem solving.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"11-20.e10"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06Epub Date: 2024-12-03DOI: 10.1016/j.cub.2024.10.067
Merybeth Fernandez Triana, Felipe Andreazza, Nadia Melo, Rickard Ignell, Ali Afify, Yuan Li, Dan-Dan Zhang, Christopher J Potter, Ke Dong, Marcus C Stensmyr
{"title":"Grapefruit-derived nootkatone potentiates GABAergic signaling and acts as a dual-action mosquito repellent and insecticide.","authors":"Merybeth Fernandez Triana, Felipe Andreazza, Nadia Melo, Rickard Ignell, Ali Afify, Yuan Li, Dan-Dan Zhang, Christopher J Potter, Ke Dong, Marcus C Stensmyr","doi":"10.1016/j.cub.2024.10.067","DOIUrl":"10.1016/j.cub.2024.10.067","url":null,"abstract":"<p><p>Humanity has long battled mosquitoes and the diseases they transmit-a struggle intensified by climate change and globalization, which have expanded mosquito ranges and the spread of associated diseases.<sup>1</sup> Additionally, widespread insecticide resistance has reduced the efficacy of current control methods, necessitating new solutions.<sup>2</sup><sup>,</sup><sup>3</sup> Nootkatone, a natural compound found in grapefruit, shows promise as both a mosquito repellent and an insecticide.<sup>4</sup><sup>,</sup><sup>5</sup> However, its mechanism of action remains unclear. Our study demonstrates that nootkatone acts as a potent spatial and contact repellent against multiple mosquito species. Nootkatone-induced spatial aversion, which is influenced by human odor, is in Aedes aegypti partially mediated by Orco- and ionotropic receptor (IR)-positive neurons, while contact aversion is robust and likely mediated via the proboscis and independent of TRPA1 and IRs. We further find that nootkatone potentiates γ-aminobutyric acid (GABA)-mediated signaling by modulating the broadly expressed major insect GABA-gated chloride channel resistant to dieldrin (Rdl). At low doses, the chemosensory-mediated spatial and contact repellency is likely strengthened by nootkatone's disruption of synaptic transmission in select mosquito sensory neurons. At higher doses, nootkatone induces paralysis and death, presumably through broad-range synaptic transmission disruption. These findings reveal nootkatone's unique mode of action and highlight its potential as an effective mosquito control agent. Its dual role as a repellent and an insecticide, combined with low-to-no toxicity to humans and a pleasant smell, underscores nootkatone's promise as a future tool in mosquito control efforts.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"177-186.e6"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06DOI: 10.1016/j.cub.2024.11.073
Sebastian Klavinskis-Whiting, Emil Fristed, Yosef Singer, M Florencia Iacaruso, Andrew J King, Nicol S Harper
{"title":"Prediction of future input explains lateral connectivity in primary visual cortex.","authors":"Sebastian Klavinskis-Whiting, Emil Fristed, Yosef Singer, M Florencia Iacaruso, Andrew J King, Nicol S Harper","doi":"10.1016/j.cub.2024.11.073","DOIUrl":"https://doi.org/10.1016/j.cub.2024.11.073","url":null,"abstract":"<p><p>Neurons in primary visual cortex (V1) show a remarkable functional specificity in their pre- and postsynaptic partners. Recent work has revealed a variety of wiring biases describing how the short- and long-range connections of V1 neurons relate to their tuning properties. However, it is less clear whether these connectivity rules are based on some underlying principle of cortical organization. Here, we show that the functional specificity of V1 connections emerges naturally in a recurrent neural network optimized to predict upcoming sensory inputs for natural visual stimuli. This temporal prediction model reproduces the complex relationships between the connectivity of V1 neurons and their orientation and direction preferences, the tendency of highly connected neurons to respond more similarly to natural movies, and differences in the functional connectivity of excitatory and inhibitory V1 populations. Together, these findings provide a principled explanation for the functional and anatomical properties of early sensory cortex.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06DOI: 10.1016/j.cub.2024.11.067
Christophe Guérin, Anne-Betty N'Diaye, Laurène Gressin, Alex Mogilner, Manuel Théry, Laurent Blanchoin, Alexandra Colin
{"title":"Balancing limited resources in actin network competition.","authors":"Christophe Guérin, Anne-Betty N'Diaye, Laurène Gressin, Alex Mogilner, Manuel Théry, Laurent Blanchoin, Alexandra Colin","doi":"10.1016/j.cub.2024.11.067","DOIUrl":"https://doi.org/10.1016/j.cub.2024.11.067","url":null,"abstract":"<p><p>In cells, multiple actin networks coexist in a dynamic manner. These networks compete for a common pool of actin monomers and actin-binding proteins. Interestingly, all of these networks manage to coexist despite the strong competition for resources. Moreover, the coexistence of networks with various strengths is key to cell adaptation to external changes. However, a comprehensive view of how these networks coexist in this competitive environment, where resources are limited, is still lacking. To address this question, we used a reconstituted system, in closed microwells, consisting of beads propelled by actin polymerization or micropatterns functionalized with lipids capable of initiating polymerization close to a membrane. This system enabled us to build dynamic actin architectures, competing for a limited pool of proteins, over a period of hours. We demonstrated the importance of protein turnover for the coexistence of actin networks, showing that it ensures resource distribution between weak and strong networks. However, when competition becomes too intense, turnover alone is insufficient, leading to a selection process that favors the strongest networks. Consequently, we emphasize the importance of competition strength, which is defined by the turnover rate, the amount of available protein, and the number of competing structures. More generally, this work illustrates how turnover allows biological populations with various competition strengths to coexist despite resource constraints.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06Epub Date: 2024-12-10DOI: 10.1016/j.cub.2024.11.021
Julian A Bustamante, Nathan D Miller, Edgar P Spalding
{"title":"Separate sites of action for cry1 and phot1 blue-light receptors in the Arabidopsis hypocotyl.","authors":"Julian A Bustamante, Nathan D Miller, Edgar P Spalding","doi":"10.1016/j.cub.2024.11.021","DOIUrl":"10.1016/j.cub.2024.11.021","url":null,"abstract":"<p><p>Rapid cell expansion pushes the Arabidopsis hypocotyl (juvenile stem) through the soil until blue light, acting first through phototropin 1 (phot1) and then through cryptochrome 1 (cry1), suppresses elongation to produce a length characteristic of established, photosynthetically capable seedlings. To determine where these two different blue-light receptors act to suppress hypocotyl elongation, we measured relative elemental growth rate, specifically along the hypocotyl midline at 5-min intervals before and during blue light, using a machine-learning-based image analysis pipeline designed specifically for this kinematic analysis of growth. In darkness, hypocotyl material expanded most rapidly (approximately 4% h<sup>-1</sup>) in a broad zone approximately 1 mm below the apical terminus of the hypocotyl (cotyledonary node). Blue light, acting through phot1, rapidly inhibited expansion in this zone, while simultaneously stimulating unexpanded cells in a very narrow, more apical region. Nuclear cry1, and not its cytoplasmic pool, counteracted the phot1-initiated expansion of the small cells in this apical region, preventing them from entering the more basal elongation zone. In a cry1 mutant, expansion of these apical cells proceeded unchecked, reaching rates as high as 6% h<sup>-1</sup> to produce the iconic cry1 long-hypocotyl phenotype. The new spatial information shows where to focus future cell and molecular studies of cry1 and phot1 signaling mechanisms and, ecologically, indicates that a seedling may use an apical reservoir of elongation potential to reenter a lit environment should a natural darkening event such as soil disturbance deactivate cry1.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"100-108.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06Epub Date: 2024-11-27DOI: 10.1016/j.cub.2024.10.070
Shinuo Weng, Masaya Hayashi, Yasuhiro Inoue, John B Wallingford
{"title":"Planar polarized force propagation integrates cell behavior with tissue shaping during convergent extension.","authors":"Shinuo Weng, Masaya Hayashi, Yasuhiro Inoue, John B Wallingford","doi":"10.1016/j.cub.2024.10.070","DOIUrl":"10.1016/j.cub.2024.10.070","url":null,"abstract":"<p><p>Convergent extension (CE) is an evolutionarily conserved developmental process that elongates tissues and organs via collective cell movements known as cell intercalation. Here, we sought to understand the mechanisms connecting cell behaviors and tissue shaping. We focus on an often-overlooked aspect of cell intercalation, the resolution of 4-cell vertices. Our data reveal that imbalanced cellular forces are involved in a timely vertex resolution, which, in turn, enables the propagation of such cellular forces, facilitating the propagation of tissue-scale CE. Conversely, delayed vertex resolution leads to a subtle but significant change in tissue-wide cell packing and exerts a profound impact by blocking force propagation, resulting in CE propagation defects. Our findings propose a collaborative nature of local cell intercalations in propagating tissue-wide CE. It unveils a multiscale biomechanical synergy underpinning the cellular mechanisms that orchestrate tissue morphogenesis during CE.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"1-10.e3"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current BiologyPub Date : 2025-01-06Epub Date: 2024-12-12DOI: 10.1016/j.cub.2024.11.027
Qing Li, Pierre Faux, Emma Wentworth Winchester, Guangrui Yang, Yingjie Chen, Luis Miguel Ramírez, Macarena Fuentes-Guajardo, Lauriane Poloni, Emilie Steimetz, Rolando Gonzalez-José, Victor Acuña, Maria-Cátira Bortolini, Giovanni Poletti, Carla Gallo, Francisco Rothhammer, Winston Rojas, Youyi Zheng, James C Cox, Vaishali Patel, Matthew P Hoffman, Li Ding, Chenchen Peng, Justin Cotney, Nicolas Navarro, Timothy C Cox, Miguel Delgado, Kaustubh Adhikari, Andrés Ruiz-Linares
{"title":"PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans.","authors":"Qing Li, Pierre Faux, Emma Wentworth Winchester, Guangrui Yang, Yingjie Chen, Luis Miguel Ramírez, Macarena Fuentes-Guajardo, Lauriane Poloni, Emilie Steimetz, Rolando Gonzalez-José, Victor Acuña, Maria-Cátira Bortolini, Giovanni Poletti, Carla Gallo, Francisco Rothhammer, Winston Rojas, Youyi Zheng, James C Cox, Vaishali Patel, Matthew P Hoffman, Li Ding, Chenchen Peng, Justin Cotney, Nicolas Navarro, Timothy C Cox, Miguel Delgado, Kaustubh Adhikari, Andrés Ruiz-Linares","doi":"10.1016/j.cub.2024.11.027","DOIUrl":"10.1016/j.cub.2024.11.027","url":null,"abstract":"<p><p>Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR, a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candidate genes. One is ∼61 kb from PITX2, a major determinant of tooth development. Another overlaps HS3ST3A1, a paralogous neighbor of HS3ST3B1, a tooth enamel knot factor. We document the expression of Pitx2 and Hs3st3a1 in enamel knot and dental epithelial cells of developing mouse incisors. Furthermore, associated SNPs in PITX2 and HS3ST3A1 overlap enhancers active in these cells, suggesting a role for these SNPs in gene regulation during dental development. In addition, we document that Pitx2 and Hs3st3a1/Hs3st3b1 knockout mice show alterations in dental morphology. Finally, we find that associated SNPs in HS3ST3A1 are in a DNA tract introgressed from Neanderthals, consistent with an involvement of HS3ST3A1 in tooth size variation during human evolution.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"131-144.e6"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}