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1.
Nature ; 598(7880): 327-331, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34588693

RESUMO

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).


Assuntos
Células da Medula Óssea/citologia , Medula Óssea , Síndrome de Down/sangue , Síndrome de Down/imunologia , Feto/citologia , Hematopoese , Sistema Imunitário/citologia , Linfócitos B/citologia , Células Dendríticas/citologia , Síndrome de Down/metabolismo , Síndrome de Down/patologia , Células Endoteliais/patologia , Eosinófilos/citologia , Células Eritroides/citologia , Granulócitos/citologia , Humanos , Imunidade , Células Mieloides/citologia , Células Estromais/citologia
2.
Immunity ; 54(11): 2650-2669.e14, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34592166

RESUMO

Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.


Assuntos
COVID-19/imunologia , Interferon-alfa/imunologia , Células Matadoras Naturais/imunologia , SARS-CoV-2/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Sequência de Bases , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Interferon-alfa/sangue , Fibrose Pulmonar/patologia , RNA-Seq , Índice de Gravidade de Doença , Transcriptoma/genética , Reino Unido , Estados Unidos
3.
Nature ; 597(7875): 250-255, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34497389

RESUMO

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.


Assuntos
Envelhecimento , Sistema Nervoso Entérico/citologia , Feto/citologia , Saúde , Intestinos/citologia , Intestinos/crescimento & desenvolvimento , Linfonodos/citologia , Linfonodos/crescimento & desenvolvimento , Adulto , Animais , Criança , Doença de Crohn/patologia , Conjuntos de Dados como Assunto , Sistema Nervoso Entérico/anatomia & histologia , Sistema Nervoso Entérico/embriologia , Sistema Nervoso Entérico/crescimento & desenvolvimento , Células Epiteliais/citologia , Feminino , Feto/anatomia & histologia , Feto/embriologia , Humanos , Intestinos/embriologia , Intestinos/inervação , Linfonodos/embriologia , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Organogênese , Receptores de IgG/metabolismo , Transdução de Sinais , Análise Espaço-Temporal , Fatores de Tempo
4.
Nat Med ; 27(5): 904-916, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33879890

RESUMO

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.


Assuntos
COVID-19/imunologia , Proteoma , SARS-CoV-2/imunologia , Análise de Célula Única/métodos , Transcriptoma , Estudos Transversais , Humanos , Monócitos/imunologia , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia
5.
Eur J Immunol ; 51(4): 764-772, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33569778

RESUMO

The development of the human immune system during embryonic and fetal life has historically been difficult to research due to limited access to human tissue. Experimental animal models have been widely used to study development but cellular and molecular programmes may not be conserved across species. The advent of multiomic single-cell technologies and an increase in human developmental tissue biobank resources have facilitated single-cell multiomic studies focused on human immune development. A critical question in the near future is "How do we best reconcile scientific findings across multiple omic modalities, developmental time, and organismic space?" In this review, we discuss the application of single-cell multiomic technologies to unravel the major cellular lineages in the prenatal human immune system. We also identify key areas where the combined power of multiomics technologies can be leveraged to address specific immunological gaps in our current knowledge and explore new research horizons in human development.


Assuntos
Desenvolvimento Embrionário/imunologia , Epigenômica/métodos , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Proteômica/métodos , Análise de Célula Única/métodos , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/imunologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
6.
Science ; 371(6527)2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33479125

RESUMO

The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.


Assuntos
Dermatite Atópica/embriologia , Dermatite Atópica/patologia , Psoríase/embriologia , Psoríase/patologia , Pele/embriologia , Animais , Atlas como Assunto , Movimento Celular , Conjuntos de Dados como Assunto , Células Dendríticas/imunologia , Dermatite Atópica/imunologia , Fármacos Dermatológicos/farmacologia , Humanos , Imunidade Inata/genética , Metotrexato/farmacologia , Camundongos , Fagócitos/imunologia , Psoríase/imunologia , Análise de Célula Única , Pele/citologia , Pele/imunologia , Linfócitos T/imunologia , Transcriptoma
7.
Can Urol Assoc J ; 15(8): E386-E392, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33410740

RESUMO

INTRODUCTION: This study aims to assess the longer-term functional, anatomical, and metabolic outcomes of patients who underwent Studer neobladder (SNB) urinary diversion. METHODS: A retrospective review of patients who underwent SNB at a single center from 1995-2017 (n=116) was performed. Demographics, comorbidities, pathological data, and longer-term functional, anatomical, and metabolic outcomes were collected from hospital records. The primary outcome was voiding function of patients at most recent followup. Secondary outcomes included postoperative complications, renal function, nephrolithiasis, infections, and metabolic outcomes. RESULTS: Excluding those with incomplete followup data, 72 patients with a minimum followup of one year were included for analysis. Median followup was 70±11 months, with 52.8% of patients having ≥5 years of followup. Clean intermittent catheterization (CIC) was used by 22.2% of patient at most recent followup, which was mostly necessitated by bladder overdistension, deteriorating renal function, or recurrent urosepsis despite timed voiding. Patients experienced more daytime and nighttime urinary incontinence in the early postoperative setting, which improved over time. Generally, renal function declined over time; poorer long-term renal function was predicted by hydronephrosis within one year (p=0.002). CONCLUSIONS: Longer-term followup of SNB reveals significant but manageable complications. Gradual decline in renal function was common. Strict adherence to bladder emptying protocols (e.g., timed voiding or CIC) may reduce incidence of renal deterioration, metabolic disorders, and urinary dysfunction. Early onset (<1 year) of hydronephrosis may indicate a need for intervention to preserve long-term renal function.

8.
Science ; 367(6480)2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32079746

RESUMO

The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα+ T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development.


Assuntos
Atlas como Assunto , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Timo/crescimento & desenvolvimento , Timo/imunologia , Linfócitos T CD8-Positivos/citologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Fibroblastos/citologia , Fibroblastos/imunologia , Humanos , RNA-Seq/métodos , Receptores de Antígenos de Linfócitos T/metabolismo , Análise de Célula Única/métodos , Timo/citologia
9.
Nature ; 574(7778): 365-371, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597962

RESUMO

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.


Assuntos
Feto/citologia , Hematopoese , Fígado/citologia , Fígado/embriologia , Células Sanguíneas/citologia , Microambiente Celular , Feminino , Feto/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Fígado/metabolismo , Tecido Linfoide/citologia , Análise de Célula Única , Células-Tronco/metabolismo
10.
Science ; 365(6460): 1461-1466, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31604275

RESUMO

Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney. We reveal anatomically defined expression patterns of immune genes within the epithelial compartment, with antimicrobial peptide transcripts evident in pelvic epithelium in the mature, but not fetal, kidney. A network of tissue-resident myeloid and lymphoid immune cells was evident in both fetal and mature kidney, with postnatal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial-immune cross-talk orchestrated localization of antibacterial macrophages and neutrophils to the regions of the kidney most susceptible to infection. Overall, our study provides a global overview of how the immune landscape of the human kidney is zonated to counter the dominant immunological challenge.


Assuntos
Rim/imunologia , Macrófagos/citologia , Neutrófilos/citologia , Adulto , Animais , Células Epiteliais/citologia , Feminino , Feto , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Rim/anatomia & histologia , Rim/citologia , Linfócitos/citologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células Mieloides/citologia , RNA-Seq , Análise de Célula Única , Infecções Urinárias/imunologia
11.
Assist Technol ; 31(4): 220-230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29370581

RESUMO

This study compared the effectiveness of two assistive technologies to accommodate the word reading skills of four middle school students with reading learning disabilities. Kurzweil 3000 is a continuous text-to-speech (TTS) computer software program that allows students to follow along on a computer monitor while passages are read aloud. A reading pen is a discontinuous TTS assistive technology (AT) device that allows students to scan and hear selected words read aloud. An adapted alternating treatments design was implemented to compare the effects of listening-while-reading using continuous TTS AT, discontinuous TTS AT, and silently reading without accommodation on reading comprehension accuracy and rate. Results indicate that in three of the four participants, continuous TTS technology led to the greatest improvements in both comprehension accuracy and rate when compared to silent reading with effect sizes reaching 0.70 and 0.99, respectively. The fourth participant demonstrated the highest comprehension accuracy and rate in the discontinuous TTS condition. The discontinuous TTS condition led to the lowest comprehension rates across all four students. Additionally, participants generally found the continuous TTS AT to be the more acceptable of the two accommodations. Discussion focuses on possible theoretical explanations for the results and implications for future research.


Assuntos
Compreensão , Leitura , Equipamentos de Autoajuda , Adolescente , Humanos , Mid-Atlantic Region , Estudantes
12.
Nature ; 563(7731): 347-353, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30429548

RESUMO

During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblast-decidual interactions underlie common diseases of pregnancy, including pre-eclampsia and stillbirth. Here we profile the transcriptomes of about 70,000 single cells from first-trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decidua reveals subsets of perivascular and stromal cells that are located in distinct decidual layers. There are three major subsets of decidual natural killer cells that have distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. Our data identify many regulatory interactions that prevent harmful innate or adaptive immune responses in this environment. Our single-cell atlas of the maternal-fetal interface reveals the cellular organization of the decidua and placenta, and the interactions that are critical for placentation and reproductive success.


Assuntos
Comunicação Celular , Feto/citologia , Histocompatibilidade Materno-Fetal/imunologia , Placenta/citologia , Placenta/metabolismo , Gravidez/imunologia , Análise de Célula Única , Comunicação Celular/imunologia , Diferenciação Celular/genética , Decídua/citologia , Decídua/imunologia , Decídua/metabolismo , Feminino , Feto/imunologia , Feto/metabolismo , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Ligantes , Placenta/imunologia , RNA Citoplasmático Pequeno/genética , Análise de Sequência de RNA , Células Estromais/citologia , Células Estromais/metabolismo , Transcriptoma , Trofoblastos/citologia , Trofoblastos/imunologia , Trofoblastos/metabolismo
13.
Nature ; 563(7730): 197-202, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30356220

RESUMO

As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response.


Assuntos
Células/metabolismo , Evolução Molecular , Imunidade Inata/genética , Imunidade Inata/imunologia , Especificidade de Órgãos/genética , Especificidade da Espécie , Transcrição Genética/genética , Animais , Células/citologia , Citocinas/genética , Humanos , Regiões Promotoras Genéticas/genética
14.
Science ; 361(6402): 594-599, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-30093597

RESUMO

Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.


Assuntos
Neoplasias Renais/genética , Neoplasias Renais/patologia , Rim/metabolismo , Transcriptoma , Adulto , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Criança , Variação Genética , Humanos , Rim/embriologia , Neoplasias Renais/classificação , Análise de Célula Única , Tumor de Wilms/classificação , Tumor de Wilms/genética , Tumor de Wilms/patologia
15.
Science ; 356(6335)2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28428369

RESUMO

Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease.


Assuntos
Células Dendríticas/classificação , Monócitos/classificação , Linfócitos T/imunologia , Adulto , Apresentação do Antígeno , Classificação , Células Dendríticas/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Ativação Linfocitária , Masculino , Monitorização Imunológica , Monócitos/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Análise de Sequência de RNA , Análise de Célula Única , Transcriptoma , Adulto Jovem
16.
PLoS One ; 12(1): e0169944, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28107476

RESUMO

Human-induced global warming and species introductions are rapidly altering the composition and functioning of Earth's marine ecosystems. Ascidians (Phylum Chordata, Subphylum Tunicata, Class Ascidiacea) are likely to play an increasingly greater role in marine communities. The colonial ascidian B. schlosseri is a cryptic species complex comprising five genetically divergent clades (A-E). Clade A is a global species, and Clade E has so far been identified in European waters only. Using the largest mitochondrial cytochrome oxidase I datasets yet assembled, we determine the origin and dispersal history of these species. Nucleotide diversity and Approximate Bayesian Computation analyses support a Pacific origin for Clade A, with two likely dispersal scenarios that both show the northwestern Atlantic populations establishing early in the history of the species. Both Discrete Phylogeographic Analysis and Approximate Bayesian Computation support an origin of Clade E on the French side of the English Channel. An unsampled lineage evolved from the French lineage, which reflects the conclusion from the median joining network that not all Clade E lineages have been sampled. This unsampled lineage gave rise to the haplotypes on the English side of the English Channel, which were the ancestors to the Mediterranean and Bay of Biscay populations. Clade E has a wider geographic range than previously thought, and shows evidence of recent range expansion. Both Clade A and Clade E should be considered widespread species: Clade A globally and Clade E within Europe.


Assuntos
Urocordados/classificação , Animais , Teorema de Bayes , Haplótipos , Filogenia , Polimorfismo Genético , Urocordados/genética
17.
Dev Comp Immunol ; 69: 60-74, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28024871

RESUMO

Allorecognition is the capability of an organism to recognize its own or related tissues. The colonial ascidian Botryllus schlosseri, which comprises five genetically distinct and divergent species (Clades A-E), contains two adjacent genes that control allorecognition: fuhcsec and fuhctm. These genes have been characterized extensively in Clade A and are highly polymorphic. Using alleles from 10 populations across the range of Clade A, we investigated the type and strength of selection maintaining this variation. Both fuhc genes exhibit higher within-population variation and lower population differentiation measures (FST) than neutral loci. The fuhc genes contain a substantial number of codons with >95% posterior probability of dN/dS > 1. fuhcsec and fuhctm also have polymorphisms shared between Clade A and Clade E that were present prior to speciation (trans-species polymorphisms). These results provide robust evidence that the fuhc genes are evolving under balancing selection.


Assuntos
Especiação Genética , Antígenos de Histocompatibilidade/metabolismo , Sistema Imunitário , Seleção Genética , Urocordados/imunologia , Animais , Evolução Molecular , Genética Populacional , Histocompatibilidade/genética , Antígenos de Histocompatibilidade/genética , Imunidade/genética , Polimorfismo Genético , Tolerância a Antígenos Próprios
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