Mutations in mitochondrial genes can disrupt key cellular functions and contribute to the development of various complex diseases. The pandemic of COVID-19, caused by the SARS-CoV-2 infection, has been associated as the cause of certain mitochondrial dysfunctions, including physiological and genetic due to infection processes as increased release of reactive oxygen species (ROS), formation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, mitophagy impairment and mitochondrial apoptotic pathway. This review compiled the main interactions between SARS-CoV-2 infection and mitochondria, highlighting mainly the genetic and immunological mechanisms that contribute to the progression of the disease and how the persistence of this inflammatory and dysfunctional state can lead to cardiac, muscular and neurological sequelae, characterizing the post COVID-19 condition.
Abstract Mercury is among the worst global pollutants being a significant public health concern in the Amazon, primarily due to contaminated fish intake. The relationship between mercury body burden and genetic polymorphisms in GSTP1 (rs1695), PON1 (rs662), MT1A (rs11076161), and SEPP1 (rs7579) genes was analyzed in Amazonian riverine populations, with a rapid and cost-effective approach by selecting individuals at both extremes of the exposure spectrum. Genotyping revealed significant associations for GSTP1 and PON1 polymorphisms: the G allele of GSTP1 and the CC genotype of PON1 were more frequent among highly exposed individuals, suggesting reduced detoxification efficiency. Additionally, although non-significant, a higher prevalence of the GG and CC genotypes were observed for MT1A and SEPP1, respectively, in the high-exposure group, pointing to the need for further investigation. These findings enhance our understanding of how genetic variation influences individual susceptibility to mercury accumulation in the Amazon and can support public health prevention strategies and the early identification of high-risk individuals within these vulnerable populations. Furthermore, this study underscores the importance of considering gene-environment interactions in environmental health assessments and highlights the need for public health strategies tailored to the genetic and socio-environmental contexts of vulnerable Amazonian communities.
Abstract Water scarcity impacts soybean cultivation and productivity globally. The ability of plants to withstand drought stress involves complex molecular and physiological mechanisms that facilitate the restoration and maintenance of cellular homeostasis. This study identified genes associated with carbohydrate metabolism and GABA shunt pathway that respond to water deficit in two soybean varieties. These varieties exhibited contrasting responses to water scarcity, and were subjected to two distinct cropping systems. In the drought-tolerant variety, a strategy for conferring tolerance was observed through the pre-emptive priming of the drought response. By applying multivariate analysis, we identified a pivotal gene, GmBAM-like 1, which responds to water scarcity. GmBAM-like 1 encodes a β-amylase and showed rapid activation and elevated expression levels in root tissues of the tolerant variety, suggesting its potential involvement in the drought tolerance response. Transgenic Arabidopsis plants overexpressing GmBAM-like 1 demonstrated enhanced tolerance to salt and osmotic stress, as evidenced by increased survival and germination rates. Additionally, after drought stress, these plants showed higher transpiration rates, larger leaf area, and greater relative water content upon rehydration. These findings demonstrate the potential of integrating the GmBAM-like 1 gene into plant breeding programs to develop cultivars with improved tolerance to water, salt, and osmotic stresses.
Abstract Virus-induced gene silencing (VIGS) has evolved from a conceptual demonstration of antiviral defense into a pivotal reverse-genetics platform for plant functional genomics. By exploiting engineered DNA- or RNA-based viral vectors, VIGS enables rapid, sequence-specific transcript knockdown through RNA-mediated degradation of target transcripts. Recent refinements in vector design, inoculation strategies, and viral species selection, such as TRV, BSMV, and FoMV, have expanded its application to previously recalcitrant plants, including major crops and emerging weed models. In weeds, functional genomics remains particularly challenging due to high genetic variability, limited genomic resources, and incompatibility with conventional viral vectors and transformation systems. In this context, VIGS provides a tractable approach to investigate genes associated with herbicide resistance, metabolic adaptation, and stress tolerance. Beyond weed biology, its application to studies of immune signaling, hormonal crosstalk, and secondary metabolism highlights VIGS as a versatile biotechnology for elucidating gene function and supporting next-generation strategies in plant improvement and integrated pest management.
Abstract Gastric adenocarcinoma (GAC) is characterized by molecular heterogeneity that limits early detection and targeted treatment. We applied weighted gene coexpression network analysis (WGCNA) to paired RNA-seq data from 119 GAC and peritumoral tissue (PTT) samples and identified six coexpression modules with distinct biological identities. Four modules were positively correlated with GAC and two were negatively correlated. Among the 30 hub genes evaluated, several outperformed established clinical biomarkers in accuracy. Specifically, SPARC (AUC = 0.89), COL3A1 (0.87), and COL1A2 (0.85) exceeded MUC5AC (0.76), VEGFA (0.68), and ERBB2 (0.64). Validation in the TCGA-STAD cohort confirmed concordant expression trends for MEblack (5/5 genes) and MEmagenta (4/5), with an overall fold-change correlation of ρ = 0.58 (p = 6.96 × 10⁻⁴). Immune deconvolution delineated two opposing microenvironmental axes, with an adaptive-immune-epithelial program (MEblack) associated with B-cell abundance, and a fibroblast-collagen program (MEmagenta) associated with cancer-associated fibroblast enrichment. DepMap CRISPR screening identified ribosomal hub genes as cell-intrinsic dependencies in gastric cancer cell lines. Among all hub genes, SPARC, COL3A1, COL1A2, GKN1, and GKN2 emerged as the potential biomarker candidates, with SPARC additionally showing a validated unfavorable prognostic association in STAD.
Abstract The cytochrome c oxidase subunit I (COI), widely adopted as a DNA barcode for Metazoa, exhibits distinct variation levels in different regions within the gene. We investigated the efficacy of combining three arthropod-specific primers to enhance the detection of dietary niches, as opposed to relying on a single primer. This study utilized bat guano collected in bat caves from the Amazon and Caatinga biomes in Brazil. The UEA2-UEA3, UEA3-UEA4, and UEA5-UEA6 primer pairs recovered distinct proportions of Arthropoda (10%, 57%, and 42%, respectively) and exhibited considerable levels of unassigned reads (29%, 33%, and 42%, respectively) and non-target sequences (61%, 10%, and 16%, respectively). The UEA2-UEA3 primarily recovered Chiroptera (57%) but demonstrated the highest taxonomic coverage and richness for Arthropoda. On the other hand, UEA3-UEA4 and UEA5-UEA6 showed the highest α-diversity for Arthropoda; however, UEA5-UEA6 predominantly recovered Lepidoptera (40%) with the highest number of unique Arthropoda genera (45%), while UEA3-UEA4 mostly assigned to Lepidoptera and Diptera. Our results suggest the use of more than one primer pair and show that the analysis of only one primer pair can generate biased outputs. The choice primer is a crucial step in eDNA studies, especially for complex samples such as bat guano.
Rhamphichthys (Gymnotiformes), a genus with uncertain taxonomy due to rarity and morphological similarity, exhibits greater diversity in the Amazon Basin. Phylogenetic analysis of COI data from specimens collected in the Amazon Basin, in Guamá River (Belém and Barcarena), Caripetuba River, and Anequara River (Abaetetuba) and deposited in the collection of the Museu Paraense Emílio Goeldi identified two major monophyletic clades within Rhamphichthys, encompassing R. pantherinus and R. rostratus. Cytogenetic analysis of 24 specimens, both with 2n=50 but differing fundamental number (FN) and karyotype formula (KF), enabled their differentiation. Although 2n=50 is likely ancestral, karyotype constitution varies among species. By combining cytogenetic and molecular data, we reclassified the previously described Rhamphichthys "marmoratus" (2n=50, FN=94, KF=44m/sm+6st/a) as R. heleios, and previous R. rostratus (2n=50, FN=92, KF=42m/sm+8st/a) as R. pantherinus. This study provides the first cytogenetic data for the real R. rostratus species and reports novel B chromosomes within the Rhamphichthyidae family.
Abstract For much of the 20th century, our understanding of genetics and evolution was predominantly shaped by intensive studies of a few model organisms such as Drosophila melanogaster, Caenorhabditis elegans, and Mus musculus. While these species provided fundamental insights, their laboratory-adapted characteristics potentially made them evolutionary outliers. The advent of next-generation sequencing technologies and sophisticated bioinformatic tools has increased accessibility of genomic research, enabling comprehensive studies of diverse non-model organisms across the tree of life. This expansion has substantially transformed our understanding of molecular evolution, revealing, for example, that convergent evolution operates through multiple mechanisms across different organizational levels, that speciation is a genomically heterogeneous process involving structural variants and adaptive introgression, and that genome architecture exhibits extensive variation in size, content, and organization. Using aquatic mammals as exemplars, we illustrate how comparative genomics of non-model species illuminates the molecular basis of convergent and divergent adaptations. This paradigm shift demonstrates that understanding evolution’s general principles and creative solutions requires embracing life’s full diversity.
Abstract Genomics has rapidly become one of the most transformative scientific approaches in modern conservation biology. As biodiversity faces increasing threats from climate change, habitat degradation, invasive species, and other human impacts, the use of genomics is providing conservation scientists with unprecedented tools to monitor biodiversity, manage endangered species, and anticipate ecological challenges. This review synthesizes recent advances in genomic applications for wildlife conservation, focusing on high-resolution whole-genome sequencing, comparative genomics, population genomics, local adaptation and environmental DNA (eDNA). The review concludes with a forward-looking discussion on integrating genomics, biodiversity monitoring, and conservation practices into a new era of comprehensive and continuous surveillance of threatened populations across diverse ecosystems.
Abstract Recurrent drought episodes, increasingly intensified by climate change, pose a growing threat to global food security by severely limiting crop productivity. Major latex-like proteins (MLPs) play crucial roles in drought tolerance, acting as regulators of stress responses. However, their involvement in adaptation to recurrent drought stress remains poorly understood. In this study, we investigated the transcriptional dynamics of MLP genes during repeated dehydration and rehydration cycles in Arachis duranensis, a tropical wild species highly resilient to drought. In silico expression profiling of 36 A. duranensis MLP genes revealed their broad involvement in recurrent drought responses, with most patterns consistent with the ‘revised-response’ category of dehydration memory genes. qRT-PCR analysis further confirmed the activation of the abscisic acid (ABA) signaling pathway during recurrent drought in A. duranensis. Functional characterization of the candidate memory gene AdMLP11 in transgenic tobacco showed that its overexpression enhances tolerance to moderate and severe recurrent drought, likely through its role as a positive regulator of phytohormone-mediated defense pathways. These findings provide novel insights into the role of MLPs in transcriptional memory and drought adaptation in wild Arachis, highlighting AdMLP11 as a promising target for biotechnological strategies to develop climate-resilient crops.
Abstract The Cichlidae family, especially the South American genus Cichla, is notable for its rapid diversification and ecological impacts following introductions outside its native range. In this study, we first describe the mitogenomes of three Cichla species. The mitogenome of Cichla piquiti was sequenced from a sample collected at Serra da Mesa Lake, located in the state of Goiás, Brazil. Additionally, the mitogenomes of Cichla monoculus and Cichla temensis were assembled using public data. The mitogenomes were assembled using NovoPlasty, and comparative analyses were performed, including those of the Cichla ocellaris mitogenome data. The mitogenomes ranged from 16,526 bp (C. monoculus) to 16,536 bp (C. piquiti), exhibiting a conserved genomic structure with 13 protein-coding genes, 22 tRNAs, and two rRNAs. These mitogenomes were validated by reconstructing phylogenetic relationships within the Cichlinae subfamily. We identified nucleotide composition biases and observed high nucleotide diversity in the D-loop region. Phylogenetic analysis based on complete mitogenome data indicated that Cichla species form a clade with C. ocellaris, a sister clade to Retroculini. This study provides new mitogenomic insights into Cichla, offering valuable genomic resources for species identification and ecological monitoring.
Over the past two decades, molecular data have revealed a complex evolutionary history for the Neotropical felid genus Leopardus. A particularly problematic subset has been the L. tigrinus complex, which has been demonstrated to comprise more than one species. Recent molecular data indicated that it is not even monophyletic, comprising distinct Leopardus lineages with a similar morphology, which likely underlies the assumption that they formed a single species. To further investigate its composition and evolutionary history, we generated mtDNA data from multiple individuals sampled in Andean regions of Colombia and Peru. The Colombian samples formed a well-supported clade that was the sister-group of the Costa Rican lineage. Remarkably, the Peruvian L. tigrinus samples formed a different clade, placed at a distinct location within the Leopardus phylogeny, as a sister-group to (L. pardalis + L. wiedii). This unexpected result extends the inference of non-monophyly of the L. tigrinus complex, and raises the possibility that additional taxonomic entities may be contained in this genus.
Abstract Ancient DNA research has expanded dramatically in recent years, transforming reconstructions of how and when humans settled the American continent. In this review, we synthesize evidence for genetic temporal continuity and discontinuity in Native American population history using mitochondrial DNA (mtDNA) from ancient and contemporary individuals. We systematically surveyed studies indexed in PubMed, ResearchGate, and Google Scholar, extending earlier compilations with publications through October 2025. For each population, we compiled sample sizes, mtDNA haplogroup frequencies, geographic coordinates, and associated archaeological and chronological information. These data were used to map the spatial distribution of founding mtDNA lineages, examine regional trajectories of haplogroup frequencies, and characterize patterns of mitochondrial population structure. Geographic distance showed a statistically detectable but limited association with mtDNA differentiation. Time-ordered haplogroup frequency series revealed region-specific dynamics, including long-term persistence of maternal lineages as well as marked episodes of turnover, some coincident with major cultural transitions. Genetic data were obtained from 315 studies. The dataset for contemporary populations included 23,315 individuals from 322 populations, while ancient DNA data included 4,192 individuals associated with 211 archaeological populations. Together, these data provide a comprehensive synthesis of mtDNA-based temporal and spatial patterns relevant to the peopling of the American continent.
The snakelike phenotype is characterized by limb reduction and body elongation, and independently evolved in several vertebrate lineages. This phenotype is often interpreted as adaptive to fossoriality or use of complex habitats. Limblessness and fossoriality might impose different energetic requirements for locomotion, affecting selective rates on mitochondrial genes. Previous studies identified signals of differential selection in mitochondrial genes of limbless lizards and fossorial rodents. However, it remains unclear which of these factors most intensely shapes mitochondrial genome evolution in Squamata. Amphisbaenia is a key group to answer this question, as it is one of the largest lineages of limbless and fossorial squamates. Here we report a new complete mitochondrial genome of Amphisbaena alba and address the relationships between limblessness and fossoriality in the evolution of mitochondrial genes in Squamata. The full length of the A. alba mitochondrial genome was 16,800 bp (13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs and the control region). We performed selective tests, allowing different rates for clades with limbless and fossorial species separately. Fossorial species have significant changes in selective rates in more mitochondrial genes than the limbless species, a result suggesting fossoriality as a prevalent factor shaping selective pressures on mitochondrial genes.
The complex interaction between nutrition, epigenetics, and epigenomics in non-communicable diseases (NCDs) such as cardiovascular diseases, obesity, type 2 diabetes mellitus (T2DM), and cancer highlights the crucial role of nutrition as an environmental factor influencing gene expression through epigenetic mechanisms such as DNA methylation, histone modifications, and regulation through non-coding RNAs (ncRNAs). The aim of this review is to explore the importance of interactions between nutrition-epigenetics interactions in the pathogenesis of NCDs and in the development of personalized prevention and treatment strategies. These nutriepigenetic and nutriepigenomic processes are fundamental for understanding the underlying molecular mechanisms of NCDs development. Diet plays a central role in modulating gene expression, and studies indicate how nutrients and bioactive compounds in food can directly affect epigenetic patterns, influencing the risk and progression of NCDs. For example, dietary effects on DNA methylation and miRNA expression have been associated with changes in susceptibility to cardiovascular diseases, obesity, and T2DM. Additionally, phytochemicals such as curcumin, genistein, quercetin, equol, among others found in certain foods can epigenetically modulate gene expression, playing a role in cancer prevention. The complexity of nutriepigenetic and nutriepigenomic systems highlights the need for a personalized approach to disease prevention and treatment. Understanding how diet influences epigenetic patterns can provide crucial insights for the development of more targeted and effective therapeutic strategies, ultimately underscoring the growing translational value of nutriepigenetics and nutriepigenomics in advancing precision medicine and informing population-level interventions, reinforcing their clinical, preventive, and societal impact in mitigating the burden of NCDs.
Metastasis is not a de novo functional module innovation but rather the pathological redeployment of deeply conserved biological programs. Here, we reconstruct the evolutionary landscape of biological functions involved in the early stages of the metastatic cascade, including cell adhesion, extracellular matrix organization (ECM), regulation of metallopeptidase activity, cell junction organization, epithelial-mesenchymal transition (EMT), and cellular extravasation alongside the physiological constraints that suppress them (Metastasis Suppressor Genes). Using phyletic pattern reconstruction of 787 orthologs across 473 Clusters of Orthologous Groups with the Bridge algorithm, we identified a divergence between the evolutionary timelines of metastasis-enabling programs and metastasis suppressors. Our results indicate that the molecular systems associated with the structural capacity for tumor dissemination are evolutionary ancient. ECM organization traces to the Human-Discoba last common ancestor, EMT to Ctenophora, cell adhesion to Sauropsida, and cellular extravasation to Actinopterygii. In contrast, mechanisms responsible for suppressing genomically unstable cells during continuous tissue renewal emerged later, peaking in the vertebrate lineage. These findings support the Serial Atavism Model and suggest that metastasis arises from the progressive erosion of recently evolved regulatory constraints, allowing the reactivation of ancestral cellular programs that predate complex multicellularity.
Abstract Obesity is a global public health issue, increasingly affecting young adults. Its association with other diseases highlights the urgency of developing prevention strategies. Genetic factors play a significant role in susceptibility to obesity, making the identification of risk-associated variants essential for prevention strategies. Therefore, this study aimed to analyze LEP, LEPR, and FTO variants as potential genetic risk factors for obesity in Brazilians aged 18-35 years. The participants were classified with, or without obesity/overweight. Genotyping was performed by ASO-PCR, RFLP, and DNA sequencing. A questionnaire was applied to collect anthropometric data, and personal and family medical history. Preliminary analyses indicated that obesity was significantly associated with individuals over 25 years of age; therefore, to specifically investigate early-onset obesity, the primary genetic association analyses were restricted to the 18-25 age group. A significant association was found between the LEP rs7799039 variant and BMI ≥ 25 Kg/m², and LEP rs17151919 was strongly associated with BMI ≥ 30 Kg/m² in this age group. These findings underscore the importance of identifying genetic variants that increase the risk of obesity in young adults and suggest contributing to the development of more effective and personalized prevention strategies, integrating knowledge from genetics, medicine, and nutrition.
Given the challenges posed by the 2019 coronavirus disease (COVID-19), understanding the role of the microbiota is crucial. The analysis of this microbial community in the body not only expands our understanding of health, but also provides insights into the interaction between viruses, microbiota, and the human host. In this study, we aimed to identify possible variations in bacterial diversity caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The study involved 45 volunteers, divided into the Positive Group (PG) consisting of 14 patients and the Negative Group (NG) consisting of 31 individuals. Both groups were stratified by biological sex to ensure sample homogeneity. Samples were collected using nasopharyngeal and oropharyngeal swabs, and total DNA was extracted and stored. The V4 region of the 16S rRNA gene was sequenced, and bioinformatics tools were used to assess the composition and diversity of the respiratory microbiota. In our results, the most abundant bacterial phyla were: Firmicutes, Bacteroidetes, and Proteobacteria. There was a notable reduction in the frequency of Firmicutes in the PG, suggesting a potential compromise in the immune response to viral infection. Beta diversity analysis did not reveal significant variations between the communities of the groups. Additionally, the analysis indicated subtle changes in some taxa, such as an increase in the abundance of Neisseriaceae in patients affected by COVID-19. These findings contribute to a deeper understanding of the complex interaction between the virus, the microbiota, and the host during infection with SARS-CoV-2, highlighting the importance of the respiratory microbiota in the context of COVID-19.
Mucopolysaccharidosis type IIIB (MPS IIIB, or Sanfilippo syndrome type B) is a lysosomal storage disorder caused by variants in the NAGLU gene, leading to heparan sulfate accumulation. This study analyzed 27 MPS IIIB Brazilian patients diagnosed via the MPS Brazil Network (2014-2022). Diagnosis involved biochemical tests [NAGLU enzyme activity, urinary glycosaminoglycans (GAG)], showing expected low activity of the enzyme and high concentration of GAGs. Molecular analysis of the NAGLU gene by Sanger sequencing or Targeted Next-Generation Sequencing confirmed the diagnosis. Forty-nine variants were found across patient alleles, comprising twenty-two different variants. Two variants were described for the first time: p.Gly79Arg and p.Leu598Pro (both missense). In silico tools predicted the novel variants as damaging/deleterious. The study identified 90.7% of the expected mutant alleles, observing variant heterogeneity and a higher frequency of missense variants. This characterization enhances understanding of the Brazilian MPS IIIB genetic landscape and is instrumental to the design of diagnostic and screening strategies.
Abstract Lung cancer is a highly prevalent disease and the leading cause of cancer-related deaths worldwide. Among non-small cell lung carcinomas (NSCLC), adenocarcinoma is one of the most common subtypes. This retrospective study aimed to analyze the prevalence of epidermal growth factor receptor (EGFR) mutations and programmed death-ligand 1 (PD-L1) expression in patients with confirmed lung adenocarcinoma, based on pathology reports from 2019 to 2024. Patients were assessed by sex, age, PD-L1 expression, and presence of EGFR and ALK mutations. A total of 895 patients were included, mostly male, with an average age of 65.85 years. EGFR mutations were identified in 24.4% of the cases, predominantly exon 19 deletions (50.2%), with women accounting for 70.3% of those mutations. PD-L1 expression, determined by the tumor proportion score (TPS), was high (TPS ≥ 50%) in 28.9%, low (1 ≤ TPS ≤ 49%) in 26.3%, and absent (TPS < 1%) in 44.8% of patients. ALK mutations were found in 5.1% of cases, mostly among younger individuals. Findings on EGFR mutations were consistent with the national and international literature. However, PD-L1 expression rates were higher than those typically reported in Brazilian studies, highlighting regional variation in biomarker prevalence.
