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Sirenians of the superorder Afrotheria were the first mammals to transition from land to water and are the only herbivorous marine mammals. Here, we generated a chromosome-level dugong (Dugong dugon) genome. A comparison of our assembly with other afrotherian genomes reveals possible molecular adaptations to aquatic life by sirenians, including a shift in daily activity patterns (circadian clock) and tolerance to a high-iodine plant diet mediated through changes in the iodide transporter NIS (SLC5A5) and its co-transporters. Functional in vitro assays confirm that sirenian amino acid substitutions alter the properties of the circadian clock protein PER2 and NIS. Sirenians show evidence of convergent regression of integumentary system (skin and its appendages) genes with cetaceans. Our analysis also uncovers gene losses that may be maladaptive in a modern environment, including a candidate gene (KCNK18) for sirenian cold stress syndrome likely lost during their evolutionary shift in daily activity patterns. Genomes from nine Australian locations and the functionally extinct Okinawan population confirm and date a genetic break ~10.7 thousand years ago on the Australian east coast and provide evidence of an associated ecotype, and highlight the need for whole-genome resequencing data from dugong populations worldwide for conservation and genetic management.
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Genoma , Mamíferos , Animais , Genoma/genética , Mamíferos/genética , Filogenia , Evolução Molecular , Organismos Aquáticos/genética , Austrália , Relógios Circadianos/genética , Evolução BiológicaRESUMO
Caloric restriction (CR) is known to extend lifespan across different species and holds great promise for preventing human age-onset pathologies. However, two major challenges exist. First, despite extensive research, the mechanisms of lifespan extension in response to CR remain elusive. Second, genetic differences causing variations in response to CR and genetic factors contributing to variability of CR response on lifespan are largely unknown. Here, we took advantage of natural genetic variation across 46 diploid wild yeast isolates of Saccharomyces species and the lifespan variation under CR conditions to uncover the molecular factors associated with CR response types. We identified genes and metabolic pathways differentially regulated in CR-responsive versus non-responsive strains. Our analysis revealed that altered mitochondrial function and activation of GCN4-mediated environmental stress response are inevitably linked to lifespan variation in response to CR and a unique mitochondrial metabolite might be utilized as a predictive marker for CR response rate. In sum, our data suggests that the effects of CR on longevity may not be universal, even among the closely related species or strains of a single species. Since mitochondrial-mediated signaling pathways are evolutionarily conserved, the dissection of related genetic pathways will be relevant to understanding the mechanism by which CR elicits its longevity effect.
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The common ancestor of all vertebrates had a highly sophisticated nervous system, but questions remain about the evolution of vertebrate neural cell types. The amphioxus, a chordate that diverged before the origin of vertebrates, can inform vertebrate evolution. Here we develop and analyse a single-cell RNA-sequencing dataset from seven amphioxus embryo stages to understand chordate cell type evolution and to study vertebrate neural cell type origins. We identified many new amphioxus cell types, including homologues to the vertebrate hypothalamus and neurohypophysis, rooting the evolutionary origin of these structures. On the basis of ancestor-descendant reconstruction of cell trajectories of the amphioxus and other species, we inferred expression dynamics of transcription factor genes throughout embryogenesis and identified three ancient developmental routes forming chordate neurons. We characterized cell specification at the mechanistic level and generated mutant lines to examine the function of five key transcription factors involved in neural specification. Our results show three developmental origins for the vertebrate nervous system: an anterior FoxQ2-dependent mechanism that is deeply conserved in invertebrates, a less-conserved route leading to more posterior neurons in the vertebrate spinal cord and a mechanism for specifying neuromesoderm progenitors that is restricted to chordates. The evolution of neuromesoderm progenitors may have led to a dramatic shift in posterior neural and mesodermal cell fate decisions and the body elongation process in a stem chordate.
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Caloric restriction (CR) is known to extend lifespan across different species and holds great promise for preventing human age-onset pathologies. However, two major challenges exist. First, despite extensive research, the mechanisms of lifespan extension in response to CR remain elusive. Second, genetic differences causing variations in response to CR and genetic factors contributing to variability of CR response on lifespan are largely unknown. Here, we took advantage of natural genetic variation across 46 diploid wild yeast isolates of Saccharomyces species and the lifespan variation under CR conditions to uncover the molecular factors associated with CR response types. We identified genes and metabolic pathways differentially regulated in CR-responsive versus non-responsive strains. Our analysis revealed that altered mitochondrial function and activation of GCN4-mediated environmental stress response are inevitably linked to lifespan variation in response to CR and a unique mitochondrial metabolite might be utilized as a predictive marker for CR response rate. In sum, our data suggests that the effects of CR on longevity may not be universal, even among the closely related species or strains of a single species. Since mitochondrial-mediated signaling pathways are evolutionarily conserved, the dissection of related genetic pathways will be relevant to understanding the mechanism by which CR elicits its longevity effect.
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PFDMO2OA (C8 HFPO-TA), a novel substitute for perfluorooctanoic acid (PFOA), has been frequently detected in surface waters. However, information on its toxicity remains scarce. In the present study, zebrafish embryos were exposed to varying concentrations of PFDMO2OA, ranging from 80 to 800 mg/L, until 120 h post-fertilization (hpf) to explore its potential developmental toxicities. The LC50 value for mortality was 505.9 mg/L, comparable to that of PFOA (over 500 mg/L), suggesting a lack of safety of PFDMO2OA compared to PFOA. At 120 hpf, PFDMO2OA exposure led to various malformations in embryos, including uninflated swim bladder, yolk sac oedema, spinal deformation, and pigmentation changes, with pericardial oedema being prominent. Analysis using O-dianisidine stain indicated a decline in erythrocytes over time. Transcriptome analysis further revealed the cardiovascular toxicity caused by PFDMO2OA at the molecular level. Time-course differential analysis pointed to the apoptosis dependent on disrupted mitochondrial function as a significant contributor to erythrocyte disappearance, as confirmed by the TUNEL stain. Therefore, the present findings suggest that PFDMO2OA induces developmental malformations and cardiovascular toxicities in zebrafish embryos, demonstrating a toxic potency comparable to that of PFOA. The results further highlight the significance of evaluating the health risks associated with PFDMO2OA.
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Embrião não Mamífero , Fluorocarbonos , Propionatos , Peixe-Zebra , Animais , Peixe-Zebra/genética , Embrião não Mamífero/anormalidades , Perfilação da Expressão Gênica , EdemaRESUMO
Molecular investigations have gathered a diverse set of mammals-predominantly African natives like elephants, hyraxes, and aardvarks-into a clade known as Afrotheria. Nevertheless, the precise phylogenetic relationships among these species remain contentious. Here, we sourced orthologous markers and ultraconserved elements to discern the interordinal connections among Afrotherian mammals. Our phylogenetic analyses bolster the common origin of Afroinsectiphilia and Paenungulata, and propose Afrosoricida as the closer relative to Macroscelidea rather than Tubulidentata, while also challenging the notion of Sirenia and Hyracoidea as sister taxa. The approximately unbiased test and the gene concordance factor uniformly recognized the alliance of Proboscidea with Hyracoidea as the dominant topology within Paenungulata. Investigation into sites with extremly high phylogenetic signal unveiled their potential to intensify conflicts in the Paenungulata topology. Subsequent exploration suggested that incomplete lineage sorting was predominantly responsible for the observed contentious relationships, whereas introgression exerted a subsidiary influence. The divergence times estimated in our study hint at the Cretaceous-Paleogene (K-Pg) extinction event as a catalyst for Afrotherian diversification. Overall, our findings deliver a tentative but insightful overview of Afrotheria phylogeny and divergence, elucidating these relationships through the lens of phylogenomics.
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Afrotheria , Mamíferos , Animais , Filogenia , Mamíferos/genéticaRESUMO
The incidence of prostate cancer (PCa), the most prevalent malignancy, is currently at the forefront. RNA modification is a subfield of the booming field of epigenetics. To date, more than 170 types of RNA modifications have been described, and N6-methyladenosine (m6A) is the most abundant and well-characterized internal modification of mRNAs involved in various aspects of cancer progression. METTL3, the first identified key methyltransferase, regulates human mRNA and non-coding RNA expression in an m6A-dependent manner. This review elucidates the biological function and role of METTL3 in PCa and discusses the implications of METTL3 as a potential therapeutic target for future research directions and clinical applications.
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Metiltransferases , Neoplasias da Próstata , Masculino , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , RNARESUMO
Despite their use as substitutes for perfluorooctanoic acid, the potential toxicities of hexafluoropropylene oxide dimer acid (HFPO-DA, commercial name: GenX) and its analogs (PFDMOHxA, PFDMO2HpA, and PFDMO2OA) remain poorly understood. To assess the hepatotoxicity of these chemicals on females, each chemical was orally administered to female C57BL/6 mice at the dosage of 0.5 mg/kg/d for 28 d. The contribution of peroxisome proliferator-activated receptors (PPARα and γ) and other nuclear receptors involving in these toxic effects of GenX and its analogs were identified by employing two PPAR knockout mice (PPARα-/- and PPARγΔHep) in this study. Results showed that the hepatotoxicity of these chemicals increased in the order of GenX < PFDMOHxA < PFDMO2HpA < PFDMO2OA. The increases of relative liver weight and liver injury markers were significantly much lower in PPARα-/- mice than in PPARα+/+ mice after GenX analog exposure, while no significant differences were observed between PPARγΔHep and its corresponding wildtype groups (PPARγF/F mice), indicating that GenX analog induce hepatotoxicity mainly via PPARα instead of PPARγ. The PPARα-dependent complement pathways were inhibited in PFDMO2HpA and PFDMO2OA exposed PPARα+/+ mice, which might be responsible for the observed liver inflammation. In PPARα-/- mice, hepatomegaly and increased liver lipid content were observed in PFDMO2HpA and PFDMO2OA treated groups. The activated pregnane X receptor (PXR) and constitutive activated receptor (CAR) pathways in the liver of PPARα-/- mice, which were highlighted by bioinformatics analysis, provided a reasonable explanation for hepatomegaly in the absence of PPARα. Our results indicate that GenX analogs could induce more serious hepatotoxicity than GenX whether there is a PPARα receptor or not. These chemicals, especially PFDMO2HpA and PFDMO2OA, may not be appropriate PFOA alternatives.
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Doença Hepática Induzida por Substâncias e Drogas , Fluorocarbonos , Propionatos , Camundongos , Feminino , Animais , Hepatomegalia/induzido quimicamente , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR gama/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fluorocarbonos/toxicidade , Fluorocarbonos/metabolismo , Camundongos Knockout , Doença Hepática Induzida por Substâncias e Drogas/genéticaRESUMO
Ustiloxins is a mycotoxin produced by the metabolism of Rice false smut. Studies have shown that Ustiloxins may be toxic to animals, but there is still a lack of toxicological evidence. The liver, as the main organ for the biotransformation of foreign chemicals, may be the direct target organ of Ustiloxins toxicity. In this study, we found that cell viability decreased in a dose- and time-dependent manner when BNL CL.2 cells were treated with different concentrations of Ustiloxins (0, 5, 10, 20, 30, 40, 60, 80, 100, 150 and 200 µg/mL) for 24 and 48 h. In addition, scanning electron microscope observation showed that the cell membrane of the experimental group was damaged, with the appearance of apoptotic bodies. Moreover, the ROS and GSH levels were significantly increased in cells exposed to Ustiloxins. We analyzed the key action targets of Ustiloxins on hepatocyte injury using full-length transcriptomics. A total of 1099 differentially expressed genes were screened, of which 473 genes were up-regulated, and 626 genes were down-regulated. Besides, we also found that the expression of MCM7 and CDC45 in BNL CL.2 cells treated with Ustiloxins decreased, and the expression of CCl-2, CYP1b1, CYP4f13, and GSTM1 increased according to qRT-PCR. Ustiloxins might change CYP450 and GST-related genes, affect DNA replication and cell cycle, and lead to oxidative stress and liver cell injury.
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Oryza , Peptídeos Cíclicos , Animais , Peptídeos Cíclicos/toxicidade , Perfilação da Expressão Gênica , Hepatócitos , Fígado/químicaRESUMO
RNA modification is a post-transcriptional level of regulation that is widely distributed in all types of RNAs, including mRNA, tRNA, rRNA, miRNA, and lncRNA, where N6-methyladenine (m6A) is the most abundant mRNA methylation modification. Significant evidence has depicted that m6A modifications are closely related to human diseases, especially cancer, and play pivotal roles in RNA transcription, splicing, stabilization, and translation processes. The most common urological cancers include prostate, bladder, kidney, and testicular cancers, accounting for a certain proportion of human cancers, with an ever-increasing incidence and mortality. The recurrence, systemic metastasis, poor prognosis, and drug resistance of urologic tumors have prompted the identification of new therapeutic targets and mechanisms. Research on m6A modifications may provide new solutions to the current puzzles. In this review, we provide a comprehensive overview of the key roles played by RNA modifications, especially m6A modifications, in urologic cancers, as well as recent research advances in diagnostics and molecularly targeted therapies.
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The timing of mammalian diversification in relation to the Cretaceous-Paleogene (KPg) mass extinction continues to be a subject of substantial debate. Previous studies have either focused on limited taxonomic samples with available whole-genome data or relied on short sequence alignments coupled with extensive species samples. In the present study, we improved an existing dataset from the landmark study of Meredith et al. (2011) by filling in missing fragments and further generated another dataset containing 120 taxa and 98 exonic markers. Using these two datasets, we then constructed phylogenies for extant mammalian families, providing improved resolution of many conflicting relationships. Moreover, the timetrees generated, which were calibrated using appropriate molecular clock models and multiple fossil records, indicated that the interordinal diversification of placental mammals initiated before the Late Cretaceous period. Additionally, intraordinal diversification of both extant placental and marsupial lineages accelerated after the KPg boundary, supporting the hypothesis that the availability of numerous vacant ecological niches subsequent to the mass extinction event facilitated rapid diversification. Thus, our results support a scenario of placental radiation characterized by both basal cladogenesis and active interordinal divergences spanning from the Late Cretaceous into the Paleogene.
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Marsupiais , Placenta , Humanos , Feminino , Gravidez , Animais , Filogenia , Marsupiais/genética , Alinhamento de Sequência/veterinária , Mamíferos/genética , Evolução BiológicaRESUMO
Background: The emerging mutants of the 2019-nCoV coronavirus are posing unprecedented challenges to the pandemic prevention. A thorough, understanding of the mutational characterization responsible for the pathogenic mechanisms of mutations in 2019-nCoV-Spike is indispensable for developing effective drugs and new vaccines. Methods: We employed computational methods and viral infection assays to examine the interaction pattern and binding affinity between ACE2 and both single- and multi-mutants of the Spike proteins. Results: Using data from the CNCB-NGDC databank and analysis of the 2019-nCoV-Spike/ACE2 interface crystal structure, we identified 31 amino acids that may significantly contribute to viral infectivity. Subsequently, we performed molecular dynamics simulations for 589 single-mutants that emerged from the nonsynonymous substitutions of the aforementioned 31 residues. Ultimately, we discovered 8 single-mutants that exhibited significantly higher binding affinities (<-65.00 kcal/mol) to ACE2 compared with the wild-type Spike protein (-55.07 kcal/mol). The random combination of these 8 single-mutants yielded 184 multi-mutants, of which 60 multi-mutants exhibit markedly enhanced binding affinities (<-65.00 kcal/mol). Moreover, the binding free energy analyses of all 773 mutants (including 589 single- and 184 multi-mutants) revealed that Y449R and S494R had a synergistic effect on the binding affinity with other mutants, which were confirmed by virus infection assays of six randomly selected multi-mutants. More importantly, the findings of virus infection assay further validated a strong association between the binding free energy of Spike/ACE2 complex and the viral infectivity. Conclusions: These findings will greatly contribute to the future surveillance of viruses and rational design of therapeutics.
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The genus Macaca includes 23 species assigned into 4 to 7 groups. It exhibits the largest geographic range and represents the most successful example of adaptive radiation of nonhuman primates. However, intrageneric phylogenetic relationships among species remain controversial and have not been resolved so far. In this study, we conducted a phylogenomic analysis on 16 newly generated and 8 published macaque genomes. We found strong evidence supporting the division of this genus into 7 species groups. Incomplete lineage sorting (ILS) was the primary factor contributing to the discordance observed among gene trees; however, we also found evidence of hybridization events, specifically between the ancestral arctoides/sinica and silenus/nigra lineages that resulted in the hybrid formation of the fascicularis/mulatta group. Combined with fossil data, our phylogenomic data were used to establish a scenario for macaque radiation. These findings provide insights into ILS and potential ancient introgression events that were involved in the radiation of macaques, which will lead to a better understanding of the rapid speciation occurring in nonhuman primates.
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Genoma , Macaca , Animais , Filogenia , Macaca/genética , Hibridização GenéticaRESUMO
Lifespan varies significantly among mammals, with more than 100-fold difference between the shortest and longest living species. This natural difference may uncover the evolutionary forces and molecular features that define longevity. To understand the relationship between gene expression variation and longevity, we conducted a comparative transcriptomics analysis of liver, kidney, and brain tissues of 103 mammalian species. We found that few genes exhibit common expression patterns with longevity in the three organs analyzed. However, pathways related to translation fidelity, such as nonsense-mediated decay and eukaryotic translation elongation, correlated with longevity across mammals. Analyses of selection pressure found that selection intensity related to the direction of longevity-correlated genes is inconsistent across organs. Furthermore, expression of methionine restriction-related genes correlated with longevity and was under strong selection in long-lived mammals, suggesting that a common strategy is utilized by natural selection and artificial intervention to control lifespan. Our results indicate that lifespan regulation via gene expression is driven through polygenic and indirect natural selection.
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Longevidade , Mamíferos , Animais , Mamíferos/classificação , Mamíferos/genética , Mamíferos/crescimento & desenvolvimento , Mamíferos/metabolismo , Longevidade/genética , Perfilação da Expressão Gênica , Expressão Gênica , Fígado/metabolismo , Encéfalo/metabolismo , Rim/metabolismo , Humanos , Masculino , FemininoRESUMO
Urological tumors, such as prostate cancer, renal cell carcinoma, and bladder cancer, have shown a significant rise in prevalence in recent years and account for a significant proportion of malignant tumors. It has been established that metastasis to distant organs caused by urological tumors is the main cause of death, although the mechanisms underlying metastasis have not been fully elucidated. The fibronectin receptor integrin α5ß1 reportedly plays an important role in distant metastasis and is closely related to tumor development. It is widely thought to be an important cancer mediator by interacting with different ligands, mediating tumor adhesion, invasion, and migration, and leading to immune escape. In this paper, we expound on the relationship and regulatory mechanisms of integrin α5ß1 in these three cancers. In addition, the clinical applications of integrin α5ß1 in these cancers, especially against treatment resistance, are discussed. Last but not least, the possibility of integrin α5ß1 as a potential target for treatment is examined, with new ideas for future research being proposed.
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The naked mole rat (Heterocephalus glaber), bats (e.g., genus Myotis), and elephants (family Elephantidae) are known as long-lived mammals and are assumed to be excellent cancer antagonists. However, whether there are common genetic changes underpinning cancer resistance in these long-lived species is yet to be fully established. Here, we newly generated a high-quality chromosome-level Asian elephant (Elephas maximus) genome and identified that the expanded gene families in elephants are involved in Ras-associated and base excision repair pathways. Moreover, we performed comparative genomic analyses of 12 mammals and examined genes with signatures of positive selection in elephants, naked mole rat, and greater horseshoe bat. Residues at positively selected sites of CDR2L and ALDH6A1 in these long-lived mammals enhanced the inhibition of tumor cell migration compared to those in short-lived relatives. Overall, our study provides a new genome resource and a preliminary survey of common genetic changes in long-lived mammals.
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Elefantes , Neoplasias , Animais , Elefantes/genética , Mamíferos/genética , Neoplasias/genética , Genômica , Cromossomos , Ratos-Toupeira/genéticaRESUMO
As the only mammalian group capable of powered flight, bats have many unique biological traits. Previous comparative genomic studies in bats have focused on long-term evolution. However, the micro-evolutionary processes driving recent evolution are largely under-explored. Using resequencing data from 50 black flying foxes (Pteropus alecto), one of the model species for bats, we find that black flying fox has much higher genetic diversity and lower levels of linkage disequilibrium than most of the mammalian species. Demographic inference reveals strong population fluctuations (>100 fold) coinciding with multiple historical events including the last glacial change and Toba super eruption, suggesting that the black flying fox is a very resilient species with strong recovery abilities. While long-term adaptation in the black flying fox is enriched in metabolic genes, recent adaptation in the black flying fox has a unique landscape where recently selected genes are not strongly enriched in any functional category. The demographic history and mode of adaptation suggest that black flying fox might be a well-adapted species with strong evolutionary resilience. Taken together, this study unravels a vibrant landscape of recent evolution for the black flying fox and sheds light on several unique evolutionary processes for bats comparing to other mammalian groups.
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Quirópteros , Animais , Quirópteros/genética , Metagenômica , Genômica , Análise de Sequência de DNA , DemografiaRESUMO
Perfluorooctane sulfonate (PFOS) and Nafion by-product 2 (H-PFMO2OSA) induce hepatotoxicity in male mice via activation of the peroxisome proliferator-activated receptor α (PPARα) pathway; however, accumulating evidence suggests that PPARα-independent pathways also play a vital role in hepatotoxicity after exposure to per- and polyfluoroalkyl substances (PFASs). Thus, to assess the hepatotoxicity of PFOS and H-PFMO2OSA more comprehensively, adult male wild-type (WT) and PPARα knockout (PPARα-KO) mice were exposed to PFOS and H-PFMO2OSA (1 or 5 mg/kg/d) for 28 d via oral gavage. Results showed that although elevations in alanine transaminase (ALT) and aspartate aminotransferase (AST) were alleviated in PPARα-KO mice, liver injury, including liver enlargement and necrosis, was still observed after PFOS and H-PFMO2OSA exposure. Liver transcriptome analysis identified fewer differentially expressed genes (DEGs) in the PPARα-KO mice than in the WT mice, but more DEGs associated with the bile acid secretion pathway after PFOS and H-PFMO2OSA treatment. Total bile acid content in the liver was increased in the 1 and 5 mg/kg/d PFOS-exposed and 5 mg/kg/d H-PFMO2OSA-exposed PPARα-KO mice. Furthermore, in PPARα-KO mice, proteins showing changes in transcription and translation levels after PFOS and H-PFMO2OSA exposure were involved in the synthesis, transportation, reabsorption, and excretion of bile acids. Thus, exposure to PFOS and H-PFMO2OSA in male PPARα-KO mice may disturb bile acid metabolism, which is not under the control of PPARα.
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Ácidos Alcanossulfônicos , Doença Hepática Induzida por Substâncias e Drogas , Fluorocarbonos , Camundongos , Masculino , Animais , PPAR alfa/genética , PPAR alfa/metabolismo , Fígado/metabolismo , Fluorocarbonos/toxicidade , Fluorocarbonos/metabolismo , Ácidos Alcanossulfônicos/toxicidade , Ácidos Alcanossulfônicos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ácidos e Sais Biliares/metabolismoRESUMO
Although previous studies have reported an association between maternal serum perfluoroalkyl substance (PFAS) exposure and gestational diabetes mellitus (GDM) risk, results have been inconsistent. Few studies have focused on the combined effects of emerging and legacy PFASs on glucose homeostasis while humans are always exposed to multiple PFASs simultaneously. Moreover, the potential pathways by which PFAS exposure induces GDM are unclear. A total of 295 GDM cases and 295 controls were enrolled from a prospective cohort of 2700 pregnant women in Shanghai, China. In total, 16 PFASs were determined in maternal spot serum samples in early pregnancy. We used conditional logistic regression, multiple linear regression, and Bayesian kernel machine regression (BKMR) to examine individual and joint effects of PFAS exposure on GDM risk and oral glucose tolerance test outcomes. The mediating effects of maternal serum biochemical parameters, including thyroid and liver function were further assessed. Maternal perfluorooctanoic acid (PFOA) exposure was associated with an increased risk of GDM (odds ratio (OR) = 1.68; 95% confidence interval (95% CI): 1.10, 2.57), consistent with higher concentrations in GDM cases than controls. Based on mediation analysis, an increase in the free triiodothyronine to free thyroxine ratio partially explained the effect of this association. For continuous glycemic outcomes, positive associations were observed between several PFASs and 1-h and 2-h glucose levels. In BKMR, PFAS mixture exposure showed a positive trend with GDM incidence, although the CIs were wide. These associations were more pronounced among women with normal pre-pregnancy body mass index (BMI). Mixed PFAS congeners may affect glucose homeostasis by increasing 1-h glucose levels, with perfluorononanoic acid found to be a main contributor. Exposure to PFASs was associated with increased risk of GDM and disturbance in glucose homeostasis, especially in normal weight women. The PFAS-associated disruption of maternal thyroid function may alter glucose homeostasis.
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Ácidos Alcanossulfônicos , Diabetes Gestacional , Poluentes Ambientais , Fluorocarbonos , Humanos , Gravidez , Feminino , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Gestantes , Estudos Prospectivos , Estudos de Casos e Controles , Teorema de Bayes , China/epidemiologia , Fluorocarbonos/toxicidade , Glucose , Ácidos Alcanossulfônicos/toxicidadeRESUMO
BACKGROUND: Although the extreme environmental adaptation of organisms is a hot topic in evolutionary biology, genetic adaptation to high-altitude environment remains poorly characterized in ectothermic animals. Squamates are among the most diverse terrestrial vertebrates, with tremendous ecological plasticity and karyotype diversity, and are a unique model system to investigate the genetic footprints of adaptation. RESULTS: We report the first chromosome-level assembly of the Mongolian racerunner (Eremias argus) and our comparative genomics analyses found that multiple chromosome fissions/fusions events are unique to lizards. We further sequenced the genomes of 61 Mongolian racerunner individuals that were collected from altitudes ranging from ~ 80 to ~ 2600 m above sea level (m.a.s.l.). Population genomic analyses revealed many novel genomic regions under strong selective sweeps in populations endemic to high altitudes. Genes embedded in those genomic regions are mainly associated with energy metabolism and DNA damage repair pathways. Moreover, we identified and validated two substitutions of PHF14 that may enhance the lizards' tolerance to hypoxia at high altitudes. CONCLUSIONS: Our study reveals the molecular mechanism of high-altitude adaptation in ectothermic animal using lizard as a research subject and provides a high-quality lizard genomic resource for future research.