Biology subjects

Briones, M. R.

Publications and source records attributed to Briones, M. R..

8 recordsLinked to original sources

bioRxiv2025

Oncogenic HPV types identified in Paleolithic and Chalcolithic human genome sequencing data from Ust'-Ishim and Ötzi

Human papillomaviruses (HPVs) are ancient viruses with diverse lineages infecting epithelial tissues in primates and humans. Although contemporary distribution and clinical importance are well understood, there is limited knowledge about their occurrence among prehistoric human populations. We investigated the presence of HPV in ancient anatomically modern humans (AMHs) by analyzing genome sequencing data from two exceptionally preserved individuals: Ust-Ishim ([~]45,000 years BP) and Otzi the Iceman ([~]5,300 years BP). Using a combination of reference-guided mapping and ancient DNA authentication criteria, we searched for HPV sequences in these ancient genomes. We detected high-confidence papillomavirus fragments in both individuals. Further phylogenetic and comparative analyses revealed that the reconstructed sequences belong to HPV16, the most oncogenic HPV lineage. Our study presents the earliest molecular evidence of HPV16 in anatomically modern humans (AMHs), pushing back its evolutionary history and challenging the idea that HPV16A entered Homo sapiens through Neanderthal interbreeding. Our results suggest that HPV16 was already present in modern humans during the Upper Paleolithic, indicating a long-standing host-virus association independent of Neanderthal transmission.

evolutionary biology↗

bioRxiv2025

SARS-CoV-2 reshapes mA methylation in long non-coding RNAs of human lung cells

N-Methyladenosine (mA) is a key base modification that regulates RNA stability and translation during viral infection. While mA methylation of host mRNAs has been studied in SARS-CoV-2-infected cells, its role in long non-coding RNAs (lncRNAs) is unknown. Here, we analyzed direct RNA sequencing (dRNA-seq) data from infected human lung cells (Calu-3) using a machine learning mA detection framework. We observed a global increase in mA levels across ten antiviral response- associated lncRNAs, with UCA1, GAS5, and NORAD--regulators of interferon (IFN) signaling-- showing the most pronounced changes. This might, in part, explain the attenuated IFN expression observed in infected cells. We identified methylated DRACH motifs in predicted lncRNA duplex-forming regions, which may favor Hoogsteen base-pairing, which destabilize secondary structures and target interaction sites. These results provide new perspectives on how SARS-CoV-2 could impact lncRNAs to modulate host immunity and viral persistence through mA-dependent mechanisms. In BriefPeter et al. show that SARS-CoV-2 infection alters mA methylation of host lncRNAs by analysis of direct RNA sequencing data with machine learning. Key immune-regulatory lncRNAs show mA alterations in RNA pairing regions, suggesting a novel mechanism by which mA may modulate antiviral responses and promote viral persistence. HighlightsO_LIDirect RNA-seq and machine learning reveal mA changes in lncRNAs C_LIO_LISARS-CoV-2 infection changes mA patterns in antiviral response-associated lncRNAs C_LIO_LILncRNAs UCA1, GAS5, and NORAD exhibit pronounced mA remodeling upon infection C_LIO_LImA sites overlap RNA duplex-forming regions in immune-regulatory lncRNAs C_LIO_LImA may impact lncRNA duplexes via Hoogsteen pairing C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/658496v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@eb2e28org.highwire.dtl.DTLVardef@236149org.highwire.dtl.DTLVardef@c82cd3org.highwire.dtl.DTLVardef@1f70f9e_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2023

Reconstructing prehistoric viral genomes from Neanderthal sequencing data

DNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals and therefore, the identification of viral genome remnants in Neanderthal sequence reads is an initial step to address this hypothesis. Here, as proof of concept, we searched for viral remnants in sequence reads of Neanderthal genome data by mapping to adenovirus, herpesvirus and papillomavirus, which are double stranded DNA viruses that may establish lifelong latency and can, produce persistent infections. The reconstructed ancient viral genomes of adenovirus, herpesvirus and papillomavirus revealed conserved segments, with nucleotide identity to extant viral genomes, and variable regions in coding regions with substantial divergence to extant close relatives. Sequence reads mapped to extant viral genomes showed deamination patterns of ancient DNA and that these ancient viral genomes showed divergence consistent with the age of these samples ({approx}50,000 years) and viral evolutionary rates (10-5 to 10-8 substitutions/site/year). Analysis of random effects shows that the Neanderthal mapping to genomes of extant persistent viruses is above the expected by random similarities of short reads. Also, negative control with a nonpersistent DNA virus does not yield statistically significant assemblies. This work demonstrates the feasibility of identifying viral genome remnants in archaeological samples with signal-to-noise assessment.

genomics↗

bioRxiv2021

Direct RNA sequencing reveals SARS-CoV-2 m6A sites and possible differential DRACH motif methylation among variants

The causative agent of COVID-19 pandemic, the SARS-CoV-2 coronavirus, has a 29,903 bases positive-sense single-stranded RNA genome. RNAs exhibit about 100 modified bases that are essential for proper function. Among internal modified bases, the N6-methyladenosine, or m6A, is the most frequent, and is implicated in SARS-CoV-2 immune response evasion. Although the SARS-CoV-2 genome is RNA, almost all genomes sequenced so far are in fact, reverse transcribed complementary DNAs. This process reduces the true complexity of these viral genomes because incorporation of dNTPs hides RNA base modifications. Here, in this perspective paper, we present an initial exploration of the Nanopore direct RNA sequencing to assess the m6A residues in the SARS-CoV-2 sequences of ORF3a, E, M, ORF6, ORF7a, ORF7b, ORF8, N, ORF10 and the 3-untranslated region. We identified 15 m6A methylated positions, of which, 6 are in ORF N. Also, because m6A is associated with the DRACH motif, we compared its distribution in major SARS-CoV-2 variants. Although DRACH is highly conserved among variants we show that variants Beta and Eta have a fourth position C>U change in DRACH at 28,884b that could affect methylation. The Nanopore technology offers a unique opportunity for the study of viral epitranscriptomics. This technique is PCR-free and is not sequencing-by-synthesis, therefore, no PCR bias and synthesis errors are introduced. The modified bases are preserved and assessed directly with no need for chemical treatments or antibodies. This is the first report of direct RNA sequencing of a Brazilian SARS-CoV-2 sample coupled with the identification of modified bases.

genomics↗

bioRxiv2018

Evolution of pathogenic and nonpathogenic yeasts mitochondrial genomes inferred by supertrees and supermatrices with divergence estimates based on relaxed molecular clocks

The evolution of mitochondrial genomes is essential for the adaptation of yeasts to the variation of environmental levels of oxygen. Although Saccharomyces cerevisiae mitochondrial DNA lacks all complex I genes, respiration is possible because alternative NADH dehydrogenases are encoded by NDE1 and NDI1 nuclear genes. The proposed whole genome duplication (WGD) in the yeast ancestor at 150-100 million years ago caused nuclear gene duplications and secondary losses, although its relation to the loss of complex I mitocondrial is unknown. Here we present phylogenomic supertrees and supermatrix tree of 46 mitochondrial genomes showing that the loss of complex I predates WGD and occurred independently in the S. cerevisiae group and the fission yeast Schizosaccharomyces pombe. We also show that the branching patterns do not differ dramatically in supertrees and supermatrix phylogenies. Our inferences indicated consistent relations between conserved mitochondrial chromosomal gene order (synteny) in closely related yeasts. Correlation of mitochondrial molecular clock estimates and atmospheric oxygen variation in the Phanerozoic suggests that the Saccharomyces lineage might have lost the complex I during hypoxic periods near Perminian-Triassic or Triassic-Jurassic mass extinction events, while the Schizosaccharomyces lineage possibly lost the complex I during hypoxic environment periods during Middle Cambrian until Lower Devonian. The loss of mitochondrial complex I during low oxygen might not affect yeast metabolism due to fermentative switch. The return to increased oxygen periods might have favored adaptations to aerobic metabolism. Additionally, we also showed that NDE1 and NDI1 phylogenies indicate evolutionary convergence in yeasts where mitochondrial complex I is absent.

genomics↗

bioRxiv2017

Inhibition of the Platelet-activating factor receptor for the treatment of Amyotrophic Lateral Sclerosis?

Cerebrospinal Fluids (CSF) of Amyotrophic Lateral Sclerosis (ALS) patients have increased levels of the inflammatory cytokine IL-18. Because IL-18 is produced by dendritic cells stimulated by the Platelet-activating factor (PAF), a major neuroinflammatory mediator, it is expected that PAF is involved in ALS. Pilot experimental data on amplification of PAF receptor (PAFR) mRNA by RT-PCR show that PAFR is overexpressed, as compared to age matched controls, in the spinal cords of transgenic ALS mouse model SOD1-G93A, suggesting PAF mediation. Although anti-inflammatory drugs have been tested for ALS before, no clinical trial has been conducted using PAFR specific inhibitors. Therefore, we hypothesize that administration of PAFR inhibitors, such as Ginkgolide B, PCA 4248 and WEB 2086, have potential to function as a novel therapy for ALS, particularly in SOD1 familial ALS forms. Because currently there are only two approved drugs with modest effectiveness for ALS therapy, a search for novel drugs and targets is essential.

neuroscience↗

bioRxiv2017

Differential distribution of Neandertal genomic signatures in human mitochondrial haplogroups

Genetic contributions of Neanderthals to the modern human genome have been evidenced by comparison of present-day human genomes with paleogenomes suggesting that the Neanderthal introgression is higher in Asians and Europeans and lower in Africans. Neanderthal signatures in extant human genomes are attributed to intercrosses between Neanderthals and archaic Anatomically Modern Humans (AMH). Although Neanderthal signatures are well documented in the nuclear genome, it has been proposed that there is no contribution of Neanderthal mitochondrial DNA to contemporary human genomes. Here we show that modern human mitochondrial genomes contain potential 66 Neanderthal signatures, or Neanderthal single nucleotide variants (N-SNVs) being 36 in coding regions of which 7 are nonsynonymous. Also, 7 N-SNVs are associated with traits such as cycling vomiting syndrome, Alzheimers disease, Parkinsons disease and 2 N-SNVs are associated with intelligence quotient. Based on recombination tests, Principal Component Analysis (PCA) and the complete absence of these N-SNVs in 41 archaic AMH mitogenomes we conclude that convergent evolution due to homoplasy and not recombination, explains the presence of N-SNVs in present-day human mitogenomes.

genomics↗

bioRxiv2017

Experimental evolution of Candida albicans under hypoxia and heat shock reveals nuclear genome variants and mitochondrial methylome alterations

Infection by Candida albicans requires its adaption to physical constraints in the human body, such as low oxygen tension (hypoxia), increased temperature (37{degrees}C) and different carbon sources. Previous studies demonstrated that the genetic variability of C. albicans isolates is an important adaptive mechanism, although little is known about the dynamics of this genetic diversity, and the influence of these environmental conditions on its mitochondrial genome (mtDNA). To test the synergistic effect of these stress conditions on C. albicans genome, reference strain SC5314 was subjected to an in vitro evolution scheme under hypoxia and 37{degrees}C, with two different carbon sources (glycerol and dextrose) for up to 48 weeks (approximately 4,000 generations). Experimental evolution results showed no sequence or copy number changes in the mtDNA, although sequence variants were detected on its nuclear genome by Multilocus sequence typing (MLST) and whole genome sequencing (WGS). After 12 weeks of experimental evolution, sample GTH12, grown under hypoxia at 37{degrees}C in glycerol, showed inferior growth and respiratory rates as compared to other conditions tested. Although WGS of GTH12 revealed no variants in its mtDNA, WGS with sodium bisulfite showed a significant reduction in mtDNA methylation in GTH12 in both non-coding and coding regions. Our results provide the first whole mitochondrial genome methylation map of C. albicans and show that environmental conditions promote the selective growth of specific variants and affect the methylation patterns of the mtDNA in a strain-specific manner.

genomics↗