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The ecological and genetic changes that underlie the evolution of host-microbe interactions remain elusive, primarily due to challenges in disentangling the variables that alter microbiome composition. To understand the impact of host habitat, host genetics, and evolutionary history on microbial community structure, we examined gut microbiomes of river- and three cave-adapted morphotypes of the Mexican tetra, Astyanax mexicanus, in their natural environments and under controlled laboratory conditions. Field-collected samples were dominated by very few taxa and showed considerable interindividual variation. We found that lab-reared fish exhibited increased microbiome richness and distinct composition compared to their wild counterparts, underscoring the significant influence of habitat. Most notably, however, we found that morphotypes reared on the same diet throughout life developed distinct microbiomes suggesting that genetic loci resulting from cavefish evolution shape microbiome composition. We observed stable differences in Fusobacteriota abundance between morphotypes and demonstrated that this could be used as a trait for quantitative trait loci mapping to uncover the genetic basis of microbial community structure.
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Physical inactivity is a scourge to human health, promoting metabolic disease and muscle wasting. Interestingly, multiple ecological niches have relaxed investment into physical activity, providing an evolutionary perspective into the effect of adaptive physical inactivity on tissue homeostasis. One such example, the Mexican cavefish Astyanax mexicanus, has lost moderate-to-vigorous activity following cave colonization, reaching basal swim speeds ~3.7-fold slower than their river-dwelling counterpart. This change in behavior is accompanied by a marked shift in body composition, decreasing total muscle mass and increasing fat mass. This shift persisted at the single muscle fiber level via increased lipid and sugar accumulation at the expense of myofibrillar volume. Transcriptomic analysis of laboratory-reared and wild-caught cavefish indicated that this shift is driven by increased expression of pparγ-the master regulator of adipogenesis-with a simultaneous decrease in fast myosin heavy chain expression. Ex vivo and in vivo analysis confirmed that these investment strategies come with a functional trade-off, decreasing cavefish muscle fiber shortening velocity, time to maximal force, and ultimately maximal swimming speed. Despite this, cavefish displayed a striking degree of muscular endurance, reaching maximal swim speeds ~3.5-fold faster than their basal swim speeds. Multi-omic analysis suggested metabolic reprogramming, specifically phosphorylation of Pgm1-Threonine 19, as a key component enhancing cavefish glycogen metabolism and sustained muscle contraction. Collectively, we reveal broad skeletal muscle changes following cave colonization, displaying an adaptive skeletal muscle phenotype reminiscent to mammalian disuse and high-fat models while simultaneously maintaining a unique capacity for sustained muscle contraction via enhanced glycogen metabolism.
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Characidae , Animais , Humanos , Characidae/genética , Evolução Biológica , Glicogênio , Músculos , México , Cavernas , MamíferosRESUMO
Voltage-dependent proton-permeable channels are membrane proteins mediating a number of important physiological functions. Here we report the presence of a gene encoding Hv1 voltage-dependent, proton-permeable channels in two species of reef-building corals. We performed a characterization of their biophysical properties and found that these channels are fast-activating and modulated by the pH gradient in a distinct manner. The biophysical properties of these novel channels make them interesting model systems. We have also developed an allosteric gating model that provides mechanistic insight into the modulation of voltage-dependence by protons. This work also represents the first functional characterization of any ion channel in scleractinian corals. We discuss the implications of the presence of these channels in the membranes of coral cells in the calcification and pH-regulation processes and possible consequences of ocean acidification related to the function of these channels.
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Antozoários/metabolismo , Canais Iônicos/metabolismo , Prótons , Animais , Recifes de Corais , Concentração de Íons de Hidrogênio , Canais Iônicos/genética , Água do Mar/químicaRESUMO
BACKGROUND: The epidermis, as a defensive barrier, is a consistent trait throughout animal evolution. During post-larval development, the zebrafish epidermis thickens by stratification or addition of new cell layers. Epidermal basal stem cells, expressing the transcription factor p63, are known to be involved in this process. Zebrafish post-larval epidermal stratification is a tractable system to study how stem cells participate in organ growth. METHODS: We used immunohistochemistry, in combination with EdU cell proliferation detection, to study zebrafish epidermal stratification. For this procedure, we selected a window of post-larval stages (5-8 mm of standard length or SL, which normalizes age by size). Simultaneously, we used markers for asymmetric cell division and the Notch signaling pathway. RESULTS: We found that epidermal stratification is the consequence of several events, including changes in cell shape, active cell proliferation and asymmetrical cell divisions. We identified a subset of highly proliferative epidermal cells with reduced levels of p63, which differed from the basal stem cells with high levels of p63. Additionally, we described different mechanisms that participate in the stratification process, including the phosphorylation of p63, asymmetric cell division regulated by the Par3 and LGN proteins, and expression of Notch genes.
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Epiderme/crescimento & desenvolvimento , Peixe-Zebra/crescimento & desenvolvimento , Animais , Diferenciação Celular , Células Epidérmicas/citologia , Epiderme/metabolismo , Fosfoproteínas/metabolismo , Transativadores/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismoRESUMO
Studying how different genotypes respond to environmental variation is essential to understand the genetic basis of adaptation. The Mexican tetra, Astyanax mexicanus, has cave and surface-dwelling morphotypes that have adapted to entirely different environments in the wild, and are now successfully maintained in lab conditions. While this has enabled the identification of genetic adaptations underlying a variety of physiological processes, few studies have directly compared morphotypes between lab-reared and natural populations. Such comparative approaches could help dissect the varying effects of environment and morphotype, and determine the extent to which phenomena observed in the lab are generalizable to conditions in the field. To this end, we take a transcriptomic approach to compare the Pachón cavefish and their surface fish counterparts in their natural habitats and the lab environment. We identify key changes in expression of genes implicated in metabolism and physiology between groups of fish, suggesting that morphotype (surface or cave) and environment (natural or lab) both alter gene expression. We find gene expression differences between cave and surface fish in their natural habitats are much larger than differences in expression between morphotypes in the lab environment. However, lab-raised cave and surface fish still exhibit numerous gene expression changes, supporting genetically encoded changes in livers of this species. From this, we conclude that a controlled laboratory environment may serve as an ideal setting to study the genetic underpinnings of metabolic and physiological differences between the cavefish and surface fish.
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Characidae/metabolismo , Transcriptoma/fisiologia , Adaptação Fisiológica/genética , Adaptação Fisiológica/fisiologia , Animais , Cavernas , Characidae/anatomia & histologia , Characidae/genética , Escuridão , Meio Ambiente , Feminino , Perfilação da Expressão Gênica , Luz , Fígado/anatomia & histologia , Fígado/metabolismo , Alinhamento de Sequência , Análise de Sequência de RNA , Transcriptoma/genéticaRESUMO
Understanding the molecular basis of repeatedly evolved phenotypes can yield key insights into the evolutionary process. Quantifying gene flow between populations is especially important in interpreting mechanisms of repeated phenotypic evolution, and genomic analyses have revealed that admixture occurs more frequently between diverging lineages than previously thought. In this study, we resequenced 47 whole genomes of the Mexican tetra from three cave populations, two surface populations and outgroup samples. We confirmed that cave populations are polyphyletic and two Astyanax mexicanus lineages are present in our data set. The two lineages likely diverged much more recently than previous mitochondrial estimates of 5-7 mya. Divergence of cave populations from their phylogenetically closest surface population likely occurred between ~161 and 191 k generations ago. The favoured demographic model for most population pairs accounts for divergence with secondary contact and heterogeneous gene flow across the genome, and we rigorously identified gene flow among all lineages sampled. Therefore, the evolution of cave-related traits occurred more rapidly than previously thought, and trogolomorphic traits are maintained despite gene flow with surface populations. The recency of these estimated divergence events suggests that selection may drive the evolution of cave-derived traits, as opposed to disuse and drift. Finally, we show that a key trogolomorphic phenotype QTL is enriched for genomic regions with low divergence between caves, suggesting that regions important for cave phenotypes may be transferred between caves via gene flow. Our study shows that gene flow must be considered in studies of independent, repeated trait evolution.
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Evolução Biológica , Cavernas , Characidae/genética , Fluxo Gênico , Genética Populacional , Animais , México , Modelos Genéticos , Fenótipo , Filogenia , Locos de Características QuantitativasRESUMO
ABSTRACT Introduction: Alzheimer's disease is a neurodegenerative disorder characterized by the loss of cognitive functions. The prevalence of this disease worldwide is high, and therefore it is important to have a better understanding of the oral health needs and conditions of individuals with this disorder. The present study was carried out in a population with E280A mutation for Alzheimer's disease. The goal was to describe the salivary characteristics of persons with early familial Alzheimer's disease, in order to detect changes in the oral microbiome that can guide the dental management of these patients. Methods: transversal study in 37 participants living in the Metropolitan Area of the city of Medellín, aged 53 ± 6 years in average, in different stages of the disease: mild: 8, moderate: 7, and severe: 22, and evaluated by neuropsychological tests. Salivary samples were collected, evaluating saliva secretion rate and saliva buffer capacity, and conducting microbial analysis of the species most commonly found in the mouth. Results: 45.9% of participants showed a decreased rate of stimulated salivary secretion; salivary buffer capacity was decreased in 83.87% of participants, with average pH values of 3.449 ± 0.89 after the Ericsson test. Buffer capacity was altered in participants with decreased secretion rate and in those with no alteration in salivary secretion rate. High levels of microbial growth were observed, mainly for Streptococcus mutans and Candida albicans. Conclusions: This study suggests that other factors besides the pharmacological ones, like age and disease severity, may affect the salivary rate flow in patients with early familial Alzheimer's disease.
RESUMEN Introducción: la enfermedad de Alzheimer es una alteración neurodegenerativa caracterizada por la pérdida de funciones cognitivas. Existe una alta prevalencia de esta enfermedad a nivel mundial, por lo que resulta oportuno tener una mayor comprensión de las necesidades y condiciones de salud bucal de los sujetos con este desorden. El presente estudio se llevó a cabo en una población con mutación E280A para la enfermedad de Alzheimer. El objetivo consistió en describir las características salivares de las personas con enfermedad de Alzheimer familiar precoz, con el fin de detectar cambios en el microbioma bucal que puedan orientar el manejo odontológico de estos pacientes. Métodos: estudio transversal en 37 participantes que habitan el Área Metropolitana de la ciudad de Medellín, con una edad promedio de 53 ± 6 años, en diferentes estadios de la enfermedad: leve: 8, moderada: 7 y grave: 22, evaluados mediante pruebas neuropsicológicas. Se tomaron muestras salivares, se evaluó la tasa de secreción salivar y la capacidad buffer de la saliva y se efectuó un análisis microbiano de las principales especies presentes en boca. Resultados: el 45,9% de los participantes presentaron una tasa disminuida de secreción salivar estimulada; la capacidad buffer salivar estuvo disminuida en el 83,87% de los participantes, con valores promedios de pH luego de la prueba de Ericsson de 3,449 ± 0,89. La capacidad buffer se encontró alterada tanto en los participantes con tasa de secreción disminuida como en aquellos con tasa de secreción salivar no alterada. Se observó alto crecimiento microbiano, principalmente de Streptococcus mutans y Candida albicans. Conclusiones: este estudio sugiere que pueden existir otros factores, además de los farmacológicos, que afectan la tasa de flujo salivar en los pacientes con enfermedad de Alzheimer familiar precoz, como la edad y la severidad de la enfermedad.
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Saliva , Doença de AlzheimerRESUMO
Chromatin regulation and organization are essential processes that regulate gene activity. The CCCTC-binding factor (CTCF) is a protein with different and important molecular functions related with chromatin dynamics. It is conserved since invertebrates to vertebrates, posing it as a factor with an important role in the physiology. In this work, we aimed to understand the distribution and functional relevance of CTCF during the embryonic development of the zebrafish (Danio rerio). We generated a zebrafish specific anti-Ctcf antibody, and found this protein to be ubiquitous, through different stages and tissues. We used the CRISPR-Cas9 system to induce molecular alterations in the locus. This resulted in early lethality. We delayed the lethality performing knockdown morpholino experiments, and found an aberrant embryo morphology involving malformations in structures through all the length of the embryo. These phenotypes were rescued with human CTCF mRNA injections, showing the specificity of the morpholinos and a partial functional conservation between the fish and the human proteins. Lastly, we found that the pro-apoptotic genes p53 and bbc3/PUMA are deregulated in the ctcf morpholino-injected embryos. In conclusion, CTCF is a ubiquitous factor during the zebrafish development, which regulates the correct formation of different structures of the embryo, and its deregulation impacts on essential cell survival genes. Overall, this work provides a basis to look for the particular functions of CTCF in the different developing tissues and organs of the zebrafish.
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Fator de Ligação a CCCTC/genética , Desenvolvimento Embrionário/genética , Animais , Apoptose/genética , Sistemas CRISPR-Cas/genética , Sobrevivência Celular/genética , Cromatina/genética , Técnicas de Inativação de Genes/métodos , Humanos , RNA Mensageiro/genética , Peixe-ZebraRESUMO
Stem cells have a high potential to impact regenerative medicine. However, stem cells in adult tissues often proliferate at very slow rates. During development, stem cells may change first to a pluripotent and highly proliferative state, known as transit-amplifying cells. Recent advances in the identification and isolation of these undifferentiated and fast-dividing cells could bring new alternatives for cell-based transplants. The skin epidermis has been the target of necessary research about transit-amplifying cells; this work has mainly been performed in mammalian cells, but further work is being pursued in other vertebrate models, such as zebrafish. In this review, we present some insights about the molecular repertoire regulating the transition from stem cells to transit-amplifying cells or playing a role in the transitioning to fully differentiated cells, including gene expression profiles, cell cycle regulation, and cellular asymmetrical events. We also discuss the potential use of this knowledge in effective progenitor cell-based transplants in the treatment of skin injuries and chronic disease.
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Famous for its blind cavefish and Darwin's finches, Latin America is home to some of the richest biodiversity hotspots of our planet. The Latin American fauna and flora inspired and captivated naturalists from the nineteenth and twentieth centuries, including such notable pioneers such as Fritz Müller, Florentino Ameghino, and Léon Croizat who made a significant contribution to the study of embryology and evolutionary thinking. But, what are the historical and present contributions of the Latin American scientific community to Evo-Devo? Here, we provide the first comprehensive overview of the Evo-Devo laboratories based in Latin America and describe current lines of research based on endemic species, focusing on body plans and patterning, systematics, physiology, computational modeling approaches, ecology, and domestication. Literature searches reveal that Evo-Devo in Latin America is still in its early days; while showing encouraging indicators of productivity, it has not stabilized yet, because it relies on few and sparsely distributed laboratories. Coping with the rapid changes in national scientific policies and contributing to solve social and health issues specific to each region are among the main challenges faced by Latin American researchers. The 2015 inaugural meeting of the Pan-American Society for Evolutionary Developmental Biology played a pivotal role in bringing together Latin American researchers eager to initiate and consolidate regional and worldwide collaborative networks. Such networks will undoubtedly advance research on the extremely high genetic and phenotypic biodiversity of Latin America, bound to be an almost infinite source of amazement and fascinating findings for the Evo-Devo community.