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Talavera, A.

Publications and source records attributed to Talavera, A..

14 recordsLinked to original sources

Hic sunt dracones: ancient DNA from the extinct palaeofauna of the tiny Mediterranean archipelago of Columbretes and its implications for human visitation

The Columbretes archipelago in the Mediterranean is an example of deep isolation and sporadic human interaction during the Holocene. We recovered ancient DNA from 2,600-year-old microfauna and historical museum specimens to investigate the island's extinct fauna. Despite challenging preservation conditions, we successfully recovered mitogenomes from historical Vipera latastei specimens, and partial mitogenomes from snake, skink, and lizard subfossils. Phylogenetic analyses confirm the extinct Columbretes snake as Vipera latastei, sharing a haplotype with the historical specimen and clustering with modern populations from northeastern Iberia, validating its provenance and suggesting a single mitochondrial lineage since isolation. The extinct skink, Chalcides bedriagai, also shows affinities with eastern Iberia. These results point to a vicariant origin for the herpetofauna, likely isolated on the island following sea level rise after the Last Glacial Maximum. Conversely, a 2,600-year-old mouse incisor yielded a Mus musculus mitogenome, indicating Iron Age human-mediated introduction. Additionally, genomic analysis of a 11th-century CE human burial revealed an individual with genetic affinities to the Central Mediterranean and Balkans, highlighting medieval maritime mobility. This study resolves the long-debated Columbretes snake identity, traces biogeographic origins and illustrates the interplay of natural isolation and anthropogenic influence on the island biodiversity.

ecology↗

Cinnamaldehyde interacts with the local anesthetic pocket of the NaV 1.5 channel

Cinnamaldehyde (CA) is extensively used as flavorant and in traditional medicine. CA is com-monly used in pain research as specific agonist of TRPA1, a polymodal cation channel expressed in nociceptive primary sensory neurons. However, we previously showed that CA inhibits the L-type Ca2+ channel in cardiac and smooth muscle cells, raising the possibility that other ion channels can be modulated by this compound as well. Here, we investigated whether CA exhibits affects the activity on the cardiac NaV1.5 channel. We used the whole-cell patch-clamp technique to record Na+ currents in HEK293T cells expressing the human NaV1.5 channel, as well as in cells expressing hNaV1.5 channels baring mutation in the binding pocket of local anesthetics (LA). Our results show that CA exhibit LA-like actions on hNaV1.5 channels: CA blocks hNaV1.5 currents in a tonic and voltage-dependent fashion. Residues F1760 and Y1767 are important for the blockade of NaV1.5 by CA and a double point mutation F1760A/Y1767A abolishes the blockade of INa by CA. We conclude that CA and LID share common structural determinants for the inhibition of Na+ channels and that CA has LA-like actions.

pharmacology and toxicology↗

Activation by statins unveils two putative agonist binding sites in the pore domain of TRPA1

TRPA1 is a non-selective cation channel that plays a crucial role in several pain and inflammatory conditions. Agents reducing membrane cholesterol decrease TRPA1 activation, but it remains unclear how cholesterol-lowering medications affect TRPA1 function. Given that TRPA1 is activated by a wide variety of chemicals, we explored whether statins have acute effects on this channel. We found that five commonly used statins activate human and mouse TRPA1 in a reversible and concentration-dependent manner. The effective concentrations were above the micromolar range, in the order: simvastatin {approx} lovastatin < fluvastatin < atorvastatin < pravastatin. Statin-induced activation was not correlated to changes in membrane order, nor mediated by N-terminal cysteine residues contributing to electrophilic compound agonism. Molecular docking calculations and the functional characterization of single-point mutants revealed two separate putative binding sites, one situated close to the kink of transmembrane segment 5 (TM5) and the other at the interface between TM4 and TM5. The mTRPA1 inhibitor A-967079 largely abrogated the response to the electrophilic agonist allyl isothiocyanate, but had weaker and varied effects across different statins and menthol. Mutation T877L strongly altered the effect of A-967079, also in an agonist-dependent manner, suggesting competitive binding between this antagonist and the non-electrophilic agonists. The identification of two distinct agonist binding sites may help explaining how TRPA1 is able to respond to a large variety of non-electrophilic compounds, while the finding of competitive interactions at one of these sites may help guide the development of agonist-specific antagonists of therapeutic relevance.

pharmacology and toxicology↗

Comparative microbiome analyses reveal differences between wild populations and captive groups of the Montseny Brook Newt (Calotriton arnoldi)

The Montseny brook newt, Calotriton arnoldi, is a Critically Endangered amphibian species endemic to the Montseny Massif in Catalonia, Northeastern Spain. Due to population declines and threats to its natural habitat, an ex-situ breeding program was initiated in 2007. A key goal of the program is to ensure the survival of captive-bred individuals after reintroduction, which in amphibians heavily relies on the specimens microbiome being capable of protecting them from environmental microorganisms, especially considering the global Chytridiomycosis pandemic caused by the fungi Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). This study aims to characterize the microbiome of wild and captive specimens of Calotriton arnoldi, to identify differences in microbiome composition, and to determine their potential impact on captive-bred individuals upon reintroduction. Up to 7,438 ASVs (Amplicon Sequence Variants) were identified from 138 samples from 21 and 61 wild and captive-bred individuals, respectively. Results indicate that wild populations from different subspecies have significantly different microbiome composition, as do wild and captive-bred groups from the same subspecies. Additionally, dissimilarities in microbiome variability were only found within each subspecies, between wild and captive-bred groups. In terms of composition, certain bacteria were identified as potential markers for both wild and captive environments. Enhancing microbiome variability might improve the survival prospects of reintroduced specimens. Thus, exposing captive specimens to a more natural environment while in captivity or a soft-release procedure could potentially mitigate the absence of exposure to other bacteria and potential pathogens from their native environment.

microbiology↗

Lizards on a sky archipelago: Genomic approaches to the evolution of the mountain genus Iberolacerta

The mountain-dwelling lizards of the genus Iberolacerta inhabit several isolated massifs across central and southwestern Europe. Their restricted and fragmented ranges, coupled with high altitude specialization in most species, entail a significant threat in the context of climate change for this group of lizards that has attracted interest from different fields. On the one hand, the alpine confinement of these relict species precedes the Pleistocene glacial cycles, and a few hypotheses have been proposed to explain it: from competitive exclusion by the wall lizards of the genus Podarcis, to adaptations to either cold or hypoxia, that would prevent them from expanding into lowlands. On the other hand, extensive research on chromosome evolution has shown Iberolacerta karyotypes to fairly differ from other lacertid lizards, exhibiting reductions in chromosome numbers and multiple sex chromosome determination systems. Here we present a chromosome-level genome assembly for Iberolacerta aurelioi, an Endangered rock lizard endemic to the Pyrenees. This genome has shed light on a genome architecture shaped by chromosome fusions, whose adaptive potential we discuss, as well as on expression shifts towards a hemoglobin isoform of enhanced oxygen affinity, as an adaptation to altitudinal hypoxia. In addition, medium coverage whole-genome sequencing data from 12 representatives encompassing all species and subspecies within the genus allowed us to address phylogenomic relationships, unveiling introgression events, gathering evidence in support of the competitive exclusion hypothesis through past demographic inference, and providing insights into homozygosity burdens, which offer valuable information for conservation efforts.

genomics↗

Unveiling the evolutionary history of European vipers and their venoms from a multi-omic approach

Snake genomes attract significant attention from multiple disciplines, including medicine, drug bioprospection, and evolutionary biology, due to the unique features found in snakes, especially, the evolution of venom. However, genomic research within the family Viperidae has mostly focused to date on the subfamily Crotalinae, while overlooking Viperinae, the Old World vipers. Among Viperinae, European vipers (Vipera) have been the subject of extensive research because of their venoms, phylogeographic, and ecological diversification. Nevertheless, venom research in this group has been conducted using mostly proteomes alone, while phylogeography and systematics in the genus have relied on biased information from mitochondrial phylogenies. Here, we generated chromosome-level genome assemblies for three Vipera species and whole-genome sequencing data for 94 samples representing 15 Vipera taxa. This comprehensive dataset has enabled us to disentangle the phylogenomic relationships of this genus, affected by mito-nuclear discordance and pervaded by ancestral introgression. Population-level analyses in the Iberian Peninsula, where the three oldest lineages within Vipera meet, revealed signals of recent adaptive introgression between ecologically dissimilar species, whereas chromosomal rearrangements isolate species occupying similar niches. Finally, using transcriptomic and proteomic data, we characterized the Vipera toxin-encoding genes, in which opposing selective forces were unveiled as common drivers of the evolution of venom as an integrated phenotype.

genomics↗

Chromosome-level reference genome for the medically important Arabian horned viper (Cerastes gasperettii)

Venoms have traditionally been studied from a proteomic and/or transcriptomic perspective, often overlooking the true genetic complexity underlying venom production. The recent surge in genome-based venom research (sometimes called "venomics") has proven to be instrumental in deepening our molecular understanding of venom evolution, particularly through the identification and mapping of toxin-coding loci across the broader chromosomal architecture. Although venomous snakes are a model system in venom research, the number of high-quality reference genomes in the group remains limited. In this study, we present a chromosome-resolution reference genome for the Arabian horned viper (Cerastes gasperettii), a venomous snake native to the Arabian Peninsula. Our highly-contiguous genome allowed us to explore macrochromosomal rearrangements within the Viperidae family, as well as across squamates. We identified the main highly-expressed toxin genes compousing the venoms core, in line with our proteomic results. We also compared microsyntenic changes in the main toxin gene clusters with those of other venomous snake species, highlighting the pivotal role of gene duplication and loss in the emergence and diversification of Snake Venom Metalloproteinases (SVMPs) and Snake Venom Serine Proteases (SVSPs) for Cerastes gasperettii. Using Illumina short-read sequencing data, we reconstructed the demographic history and genome-wide diversity of the species, revealing how historical aridity likely drove population expansions. Finally, this study highlights the importance of using long-read sequencing as well as chromosome-level reference genomes to disentangle the origin and diversification of toxin gene families in venomous species.

genomics↗

Hidden in the sand: phylogenomics unravel an unexpected evolutionary history on the desert-adapted vipers of the genus Cerastes

The desert vipers of the genus Cerastes are a small clade of medically important venomous snakes within the family Viperidae. According to published morphological and molecular studies, the group is comprised by four species: two morphologically similar and phylogenetically sister taxa, the African horned viper (Cerastes cerastes) and the Arabian horned viper (Cerastes gasperettii); a more distantly related species, the Saharan sand viper (Cerastes vipera), and the enigmatic Bohmes sand viper (Cerastes boehmei), only known from a single specimen in captivity allegedly captured in Central Tunisia. In this study, we analyzed one mitochondrial marker (COI) as well as genome-wide data (ddRAD sequencing) from 28 and 41 samples, respectively, covering the entire distribution range of the genus to explore the population genomics, phylogenomic relationships and introgression patterns within the genus Cerastes. Additionally, and to provide insights into the mode of diversification of the group, we carried out niche overlap analyses considering climatic and habitat variables. Both nuclear phylogenomic reconstructions and population structure analyses have unveiled an unexpected evolutionary history for the genus Cerastes, which sharply contradicts the morphological similarities and previously published mitochondrial approaches. Cerastes cerastes and C. vipera are recovered as sister taxa whilst C. gasperettii is a sister taxon to the clade formed by these two species. We found a relatively high niche overlap (OI > 0.7) in both climatic and habitat variables between C. cerastes and C. vipera, contradicting a potential scenario of sympatric speciation. These results are in line with the introgression found between the northwestern African populations of C. cerastes and C. vipera. Finally, our genomic data confirms the existence of a lineage of C. cerastes in Arabia. All these results highlight the importance of genome-wide data over few genetic markers to study the evolutionary history of species.

genomics↗

The origin of a mountain biota: hyper-aridity shaped reptile diversity in an Arabian biodiversity hotspot

Advances in genomics have greatly enhanced our understanding of mountain biodiversity, providing new insights into the complex and dynamic mechanisms that drive the formation of mountain biotas. These include from broad biogeographic patterns, to population dynamics and adaptations to these environments. However, significant challenges remain in integrating these large-scale and fine-scale findings to develop a comprehensive understanding of mountain biodiversity. One significant challenge is the lack of genomic data, particularly in historically understudied arid regions where reptiles are a particularly diverse vertebrate group. We generated de novo genome-wide SNP data for more than 600 specimens and integrated state-of-the-art biogeographic analyses at the community, species and population level. We, thus, provide for the first time, a holistic integration of how a whole endemic reptile community has originated, diversified and dispersed through a mountain range. Our results show that reptiles independently colonized the Hajar Mountains of eastern Arabia 11 times. After colonization, species delimitation methods suggest high levels of within-mountain diversification, supporting up to 49 putative species. This diversity is strongly structured following local topography, with the highest peaks acting as a broad barrier to gene flow among the entire community. Surprisingly, orogenic events do not seem to rise as key drivers of the biogeographic history of reptiles in this system. However, paleoclimate seems to have had a major role in this community assemblage. We observe an increase of vicariant events from Late Pliocene onwards, coinciding with an unstable climatic period of rapid shifts between hyper-arid to semiarid conditions that led to the ongoing desertification of Arabia. We conclude that paleoclimate, and particularly extreme aridification, acted as a main driver of diversification in arid mountain systems which is tangled with the generation of highly adapted endemicity. Our study provides a valuable contribution to understanding the evolution of mountain biodiversity and the role of environmental factors in shaping the distribution and diversity of reptiles in arid regions.

evolutionary biology↗

Species boundaries to the limit: validating species delimitation methods is critical to avoid taxonomic inflation in the genomic era

With the advent of molecular phylogenetics, the number of taxonomic studies unveiling and describing cryptic diversity has greatly increased. However, speciation between cryptic lineages is often defined without evaluating population structure or gene flow, which can lead to false claims of species status and, subsequently, taxonomic inflation. In the present study we focus on the intriguing case of the Arabian gecko Trachydactylus hajarensis (Squamata: Gekkonidae), a species for which cryptic diversity has been previously reported. We generated mitochondrial data (12S rDNA) and genome-wide SNP data (ddRADseq) for 52 specimens to determine phylogenomic relationships, population structure and gene flow within this species. Then, we applied species delimitation methods (SDMs) to evaluate several competing species hypotheses through the Multispecies Coalescent model. Results show that T. hajarensis is comprised by three well-defined lineages, two of them in the Hajar Mountains of eastern Arabia, and one in Masirah Island, in the southeastern coast of Oman. Even though high levels of past introgression and strong mitonuclear discordances were found, current gene flow is scarce with clear boundaries between populations and shallow levels of admixture in the contact zone between lineages. Surprisingly, species tree topology differed between methods and when different individuals were used in downsampled datasets. Conventional SDMs supported up to three putative new species within the group. However, after species validation with the genealogical divergence index (gdi), none of the putative species held. Overall, this study highlights the importance of sample choice, integrative analyses, and validation methods to not incur into taxonomic inflation, providing a set of already available tools to assess and validate population structure, gene flow, and SDMs before describing new species.

evolutionary biology↗

Evolution along allometric lines of least resistance: Morphological differentiation in Pristurus geckos

Species living in distinct habitats often experience unique ecological selective pressures, which can drive phenotypic divergence. However, how ecophenotypic patterns are affected by allometric trends and trait integration levels is less well understood. Here we evaluate the role of allometry in shaping body size and shape diversity in Pristurus geckos utilizing differing habitats. We found that patterns of body shape allometry and integration were distinct in species with different habitat preferences, with ground-dwelling Pristurus displaying the most divergent allometric trend and the strongest integration. There was also strong concordance between static allometry across individuals and evolutionary allometry among species, revealing that body shape differences among individuals were predictive of evolutionary changes across the phylogeny at macroevolutionary scales. This suggested that phenotypic evolution occurred along allometric lines of least resistance, with allometric trajectories imposing a strong influence on the magnitude and direction of size and shape changes across the phylogeny. When viewed in phylomorphospace, the largest rock-dwelling species were most similar in body shape to the smallest ground-dwelling species, and vice versa. Thus, in Pristurus, phenotypic evolution along the differing habitat-based allometric trajectories resulted in similar body shapes at differing body sizes in distinct ecological habitats.

evolutionary biology↗

Genomics reveals introgression and purging of deleterious mutations in the Arabian leopard (Panthera pardus nimr)

Low genetic variation and high levels of inbreeding are usually a consequence of recent population declines in endangered species. From a conservation point of view, it is essential to genetically screen endangered populations to help assess their vulnerability to extinction and to properly create informed management actions towards their conservation efforts. The leopard, Panthera pardus, is a highly generalist predator with currently eight different subspecies inhabiting a wide range of habitats. Yet, genomic data is still lacking for the Critically Endangered Arabian leopard (P. p. nimr). Here, we sequenced the whole genome of two specimens of Arabian leopard and assembled the most complete genomic dataset for leopards to date, including genomic data for all current subspecies. Our phylogenomic analyses show that leopards are divided into two deeply divergent clades, one including the only African subspecies and a second one including all seven subspecies of Asian leopards. Interestingly, the Arabian leopard represents a well-differentiated lineage sister to the rest of Asian subspecies. The demographic history, genomic diversity, Runs of Homozygosity (RoHs), and mutational load in the Arabian leopard indicate a prolonged population decline, which has led to an increase in inbreeding and RoHs, with consequent purging of deleterious mutations. Our study represents the first attempt to genetically inform captive breeding programs for this Critically Endangered subspecies. Still, more genomes, particularly from wild individuals, are needed to fully characterise the genetic makeup of this singular and iconic subspecies.

genomics↗

Direct activation of an innate immune system in bacteria by a viral capsid protein

Bacteria have evolved sophisticated and diverse immunity mechanisms to protect themselves against a nearly constant onslaught of bacteriophages1-3. Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns (PAMPs)4, many bacterial immune systems that respond to bacteriophage infection require a phage-specific trigger to be activated. However, the identities of such triggers and the mechanistic basis of sensing remain almost completely unknown. Here, we discover and investigate the anti-phage function of a fused toxin-antitoxin (TA) system called CapRelSJ46 that protects E. coli against diverse phages. Through genetic, biochemical, and structural analysis, we demonstrate that the C-terminal domain of CapRelSJ46 regulates the toxic N-terminal region, serving as both an antitoxin element and a phage-infection sensor. Following infection by certain phages, the newly synthesized major capsid protein binds directly to the C-terminal domain of CapRelSJ46 to relieve autoinhibition, enabling the toxin domain to then pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for TA-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a Red Queen conflict5, revealing a new front in the intense coevolutionary battle being waged by phage and bacteria. With capsid proteins of some eukaryotic viruses known to stimulate innate immune signaling in mammalian hosts6-10, our results now reveal an ancient, deeply conserved facet of immunity.

microbiology↗

Nucleotide-mediated allosteric regulation of bifunctional Rel enzymes

Bifunctional Rel stringent factors, the most broadly distributed class of RSHs, are ribosome-associated enzymes that transfer a pyrophosphate group from ATP onto the 3' of GTP or GDP to synthesize (p)ppGpp and also catalyse the 3' pyrophosphate hydrolysis of the alarmone to degrade it. The precise regulation of these enzymes seems to be a complex allosteric mechanism, and despite decades of research, it is unclear how the two opposing activities of Rel are controlled at the molecular level. Here we show that a stretch/recoil guanosine-switch mechanism controls the catalytic cycle of T. thermophilus Rel (RelTf). The binding of GDP/ATP stretches apart the NTD catalytic domains of RelTf (RelTtNTD) activating the synthetase domain and allosterically blocking the hydrolase active site. Conversely, binding of ppGpp unlocks the hydrolase domain and triggers recoil of both NTDs, which partially buries the synthetase active site and precludes the binding of synthesis precursors. This allosteric mechanism acts as an activity switch preventing futile cycles of alarmone synthesis and degradation.

molecular biology↗