Biology subjects

Beltran-Alvarez, P.

Publications and source records attributed to Beltran-Alvarez, P..

6 recordsLinked to original sources

bioRxiv2026

Type I PRMTs Play a Role in Mammalian Embryonic Lineage Specification

Mammalian preimplantation development requires precisely coordinated lineage decisions to establish the trophectoderm (TE), inner cell mass (ICM), epiblast (EPI), and primitive endoderm (PrE). Glucose metabolism and epigenetic regulation are increasingly recognised as key determinants of lineage specification during preimplantation development. However, how glucose-dependent metabolic cues interface with epigenetic mechanisms to regulate embryonic cell fate remains poorly understood. Here, we investigated the role of glucose in regulating protein methylation by protein arginine methyltransferases (PRMT) in bovine preimplantation development. PRMT1 and its associated histone mark H4R3me2a were detected throughout bovine oocyte maturation and embryo development. Pharmacological inhibition of Type I PRMTs using two structurally distinct inhibitors, GSK3368715 and MS023, markedly reduced global protein asymmetric dimethylarginine (ADMA) and H4R3me2a levels. PRMT inhibition impaired blastocyst cell proliferation, reduced total cell number, and disrupted both first and second lineage decisions, as demonstrated by decreased CDX2- and SOX2-positive TE and ICM cells and reduced NANOG- and GATA6-positive EPI and PrE cell allocation. Mechanistically, Type I PRMT inhibition downregulated key components of the Hippo-associated TE programme, including YAP, TEAD4, and TFAP2C. Consistent effects were observed in mouse embryos, where MS023 treatment reduced ADMA, CDX2, YAP, and TFAP2C expression and impaired TE and ICM allocation. Collectively, our findings identify Type I PRMT-mediated ADMA as an essential epigenetic regulator of early mammalian lineage specification and support a conserved ADMA-Hippo regulatory axis linking arginine methylation to embryonic cell fate decisions. In briefType I protein arginine methyltransferase (PRMT)-mediated asymmetric dimethylarginine (ADMA) is required for proper lineage specification during mammalian preimplantation development. ADMA depletion disrupts Hippo signalling, cell proliferation, and trophectoderm and inner cell mass allocation in bovine and mouse embryos.

developmental biology↗

bioRxiv2024

Climate drives long-term landscape and rapid short-term promoter evolution in the Western Canaries lizard, Gallotia galloti

Climate adaptation is caused by multiple mechanisms, including evolution of regulatory promoter sequences under broad environmental pressures, however, little is known about these processes in response to climate pressures in animals. Here, we examined spatial and temporal evolution of climate-related gene promoters in an insular species, the Western-Canaries lizard Gallotia galloti, across diverse environmental conditions over nine years. Outlier SNPs linked to elevation-sensitive environmental factors identified adaptively significant loci, including in aquaporin and Electron Transfer Flavoprotein Subunit Alpha (ETFA) gene promoters, demonstrating roles in local climate adaptation. Adaptive indexing mapped climate-driven genetic differentiation across the landscape, revealing local adaptation along an elevational gradient. Signatures of climate-related selection at the temporal scale showed specific promoters shaped by balancing selection supporting survival across environments, while others experienced positive selection, revealing a selective sweep of beneficial alleles. In addition, elevation-based ancestry groups of climate loci differed from the pattern observed in neutral loci, and temporal shifts in ancestry composition responded to preceding extreme weather events over the span of a single generation. Selection on specific promoter regions indicated adaptive evolution in transcription factor binding sites with the potential to enhance transcriptional flexibility, resulting in increased cellular stress tolerance. Our findings open new avenues into genomic mechanisms of resilience across spatially heterogeneous environments and how rapid evolution correlates with extreme weather events associated with climate change.

evolutionary biology↗

bioRxiv2023

Consequences of directly- and indirectly-experienced heat stress in a mutagenic environment

Climate change increases the frequency and duration of heat events. Negative effects of heat stress may be exacerbated through the action of social metabolites between aquatic animals. Whilst early life stages are vulnerable to stress-induced damage, they deploy cellular mechanisms to protect cells against mutagens such as ultraviolet rays (UV). Little is known about the fate of fish embryos which have experienced heat stress in a mutagenic environment. The present study exposed zebrafish embryos to one of three stress history treatments consisting of direct heat stress (TS+UV), the social context of heat stress via social metabolites (SM+UV), and their combination in TS+SM+UV before a UVB/UVA damage/repair assay. We measured phenotypic and transcriptomic responses to these treatments, and estimated mutational damage through DNA mutation frequencies and RNA integrity values. Compared to UV-treated controls (C+UV), the social context of heat stress history preceding the UV assay altered keratin and cell structuring-related pathways, associated with longer embryos with over-developed pericardia displaying behavioural hypoactivity. Relative to C+UV, direct heat stress history preceding UV exposure had a hormetic effect by stimulating the cellular stress response and facilitating DNA repair, which rescued embryos from subsequent UV damage and improved their apparent fitness. However, heat stress combined with social metabolites overwhelmed embryos in the UV assay, which annihilated the hormetic effect, introduced mutations, and lowered their apparent fitness. Whilst generated in the laboratory, these findings provide an important baseline for understanding the consequences of heat stress history in natural environments, where heat stress occurs within a social context. HighlightsO_LIHeat stress had a hormetic effect against UV damage, by stimulating the heat shock response, antioxidants, and DNA repair. C_LIO_LIThe heat hormetic effect protected and/or rescued embryos from UV damage by reducing single nucleotide variants observed in RNA, lowering malformations, and accelerating development. C_LIO_LIHeat-stressed embryos released social metabolites that initiated keratin, immune, and cellular structuring responses in receivers, in turn increasing body sizes but without reducing UV-induced malformations. C_LIO_LIHeat combined with social metabolites overwhelmed embryos in response to UV, reducing fitness-relevant performance. C_LIO_LIHeat stress during early embryogenesis led to differential fitness-relevant outcomes showing a nonlinear relationship with stress intensity. C_LI Summary statementSublethal heat stress protects zebrafish embryos in a mutagenic environment, but this protective effect is lost when zebrafish embryos additionally stress each other via chemical cues. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/560724v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@a6445org.highwire.dtl.DTLVardef@3cfc64org.highwire.dtl.DTLVardef@1de41c6org.highwire.dtl.DTLVardef@b06269_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2022

Heat induces multi-omic and phenotypic stress propagation in zebrafish embryos

Heat alters biology from molecular to ecological levels, but may also have unknown indirect effects. This includes the novel concept that animals exposed to abiotic stress can induce stress in naive receivers. Here, we provide a comprehensive picture of the molecular signatures of this process, by integrating multi-omic and phenotypic data. In individual zebrafish embryos, repeated heat peaks elicited both a molecular response and a burst of accelerated growth followed by a growth slow-down in concert with reduced responses to novel stimuli. Metabolomes of the media of heat treated vs. untreated embryos revealed candidate stress metabolites including sulphur-containing compounds and lipids. These stress metabolites elicited transcriptomic changes in naive receivers related to immune response, extracellular signalling, glycosaminoglycan/keratan sulphate, and lipid metabolism. Consequently, non heat-exposed receivers (exposed to stress metabolites only) experienced accelerated catch-up growth in concert with reduced swimming performance. The combination of heat and stress metabolites accelerated development the most, mediated by apelin signalling. Our results prove the concept of indirect heat-induced stress propagation towards naive receivers, inducing phenotypes comparable to those resulting from direct heat exposure, but utilising distinct molecular pathways. Group-exposing a non-laboratory zebrafish line, we independently confirm that the glycosaminoglycan biosynthesis-related gene chs1, and the mucus glycoprotein gene prg4a, functionally connected to the candidate stress metabolite classes sugars and phosphocholine, are differentially expressed in receivers. This hints at production of Schreckstoff-like cues in receivers, leading to further stress propagation within groups, which may have ecological and animal welfare implications for aquatic populations in a changing climate. Significance StatementAquatic animals utilise chemicals to mediate adaptive behaviours. For instance, predated fish release chemical cues that elicit antipredatory responses in naive receivers. But whether abiotic factors such as heat likewise alter chemical communication has received little focus. Here, we uncover a novel dimension of chemical communication -- heat-stressed donors can induce stress in naive receivers. We show that heat activates molecular stress responses, leading to the release of distinct stress metabolite classes into the environment. These stress metabolites alter the transcriptome of receivers, resulting in faster development and hypoactivity. Heat combined with stress metabolites had the largest effect, highlighting that abiotic stress, experienced both directly and indirectly, can alter chemical communication and affect embryonic development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/508176v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1e44b4borg.highwire.dtl.DTLVardef@10b6878org.highwire.dtl.DTLVardef@1f7c3bforg.highwire.dtl.DTLVardef@15436bc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe elucidate the mechanism for a novel dimension of the heat stress response -- chemical communication from heat-stressed donors that induces stress in naive receivers -- constituting a positive feedback loop C_LIO_LIRepeated heat stress induces a cellular and cortisol stress response and alters the phenotype of zebrafish embryos C_LIO_LIHeat-stressed embryos release stress metabolites enriched in lipids and sulphur-containing organo-oxygen compounds C_LIO_LIIn combination, heat and stress metabolites induced 47% distinct differentially expressed genes, with many related to organ development C_LIO_LIThese stress metabolites alter the transcriptome and induce both faster development and hypoactivity in naive receivers, a similar response to that of heat stress itself C_LI

molecular biology↗

bioRxiv2021

Thermal stress induces positive phenotypic and molecular feedback loops in zebrafish embryos

Aquatic organisms must cope with both rising and rapidly changing temperatures. These environmental changes can affect numerous traits, from molecular to ecological scales. Biotic stressors can induce the release of chemical cues which trigger behavioural responses in other individuals. In this study, we infer whether abiotic stressors, such as fluctuating temperature, may similarly propagate stress responses between individuals in fish not directly exposed to the stressor. To test this hypothesis, zebrafish (Danio rerio) embryos were exposed for 24 hours to fluctuating thermal stress, to medium in which another embryo was thermally stressed before ("stress medium"), and to a combination of these. Growth, behaviour, and expression of a panel of genes were used to characterise the thermal stress response and its propagation between embryos. Both high temperatures and stress medium significantly accelerated development and altered embryonic behaviour. Thermal stress significantly decreased the expression of the antioxidant gene SOD1, eight hours after the end of exposure. Of note, we found that the expression of sulfide:quinone oxidoreductase (SQOR), likewise a part of the antioxidant metabolism relevant in vertebrate stress response, and of interleukin-1{beta} (IL-1{beta}), involved in the immune response, were significantly altered by stress medium. This study illustrates the existence of positive thermal stress feedback loops in zebrafish embryos that induce stress in conspecifics. This evidence that thermal stress due to fluctuating, high temperatures can be propagated may be relevant for species found in high densities, either in aquaculture or in the natural environment, in a context of global change.

physiology↗

bioRxiv2019

Abiotic environmental adaptation in vertebrates is characterized by functional genomic constraint

Understanding the genomic basis of adaptation to different abiotic environments is important for understanding organismal responses to current short-term environmental fluctuations. Using functional and comparative genomics approaches, we here investigated whether genomic adaptation to a set of environmental parameters is contingent across vertebrate genomes or, alternatively, contains an element of evolutionary constraint that would be evident through recurrent involvement of specific subsets of genes and functions in adaptation to similar environments. We first identified 200 genes with signatures of selection from transcriptomes of 24 species of lacertid lizards with known adaptations in preferred temperature, correlated with thermal environment experienced by these lizards in their range. In order to discern genes adapting to climate from other selective factors, we then performed a meta-analysis of 1100 genes with signatures of selection obtained from-omics studies in vertebrate species adapted to different abiotic environments. We found that this gene set formed a tightly connected interactome which was to 23% enriched in predicted functions of adaptation to climate and to 18% involved in organismal stress response. We found a much higher degree of recurrent use of identical genes (43.6%) and functional similarity than expected by chance, and no clear division between genes used in ectotherm and endotherm physiological strategies. 171 out of 200 genes of Lacertidae were part of this network, indicating that a comparative genomic approach can help to disentangle genes functionally related to adaptation to different abiotic environments from other selective factors. These results furthermore highlight an important role of genomic constraint in adaptation to the abiotic environment, and narrows the set of candidate markers to be used in future research on environmental adaptability related to climate change.\n\nSignificance Statement / Nontechnical summaryWhile the convergent evolution of phenotypes in similar environments is a well-studied phenomenon, the genomic basis of such common phenotypes and physiologies is still enigmatic. The prevalent notion is that re-use of the same genes to adapt to similar environments in different species is about as likely as winning the lottery - but organismal systems are also, to some extent, comparable between different species such as man and fruit fly through shared genes and gene functions. In this paper, we test whether constraint or contingency is more prevalent in genomic adaptation of vertebrates to aspects of their abiotic environment. We find evidence for strong functional constraint and stress responsiveness of the genes involved, which might help understand how currently experienced stress under changing climates may result in future adaptation.

evolutionary biology↗