Biology subjects

Santos, M. A.

Publications and source records attributed to Santos, M. A..

7 recordsLinked to original sources

bioRxiv2026

Painting the evolutionary history of a multicompartmentalized syngameon in North American Castilleja (Orobanchaceae)

Understanding the evolutionary history of recent rapidly radiating groups remains a major challenge in systematics, especially when incomplete reproductive isolation and rampant interspecific gene flow obscure phylogenetic signal. Here, we present a comprehensive phylogenomic study of the genus Castilleja (the paintbrushes, Orobanchaceae), integrating nuclear and chloroplast data to investigate patterns of diversification, hybridization, and geographic structure across its range. Our results provide the first evidence that Castilleja functions as a multicompartmentalized syngameon-a network of closely related species with ongoing or historical gene flow among non-sister lineages within and between geographically structured compartments. High nuclear gene tree discordance, coupled with strong cpDNA geographic compartment structuring and nuclear network analysis, supports the hypothesis that recent rapid radiation and Plio-Pleistocene climatic fluctuations created alternating periods of range expansion and contraction. These dynamics likely promoted localized hybridization within isolated compartments during contraction and further introgression between compartments during range expansion. Our findings not only clarify the evolutionary relationships within Castilleja but also demonstrate the importance of genome-scale data and syngameon theory in understanding diversification in lineages where hybridization is rampant.

evolutionary biology↗

bioRxiv2024

Monandrous flies do remate: plastic and evolutionary consequences of heat exposure on mating behaviour and fertility in Drosophila subobscura

Recent work has reinforced the importance of fertility in predicting population persistence under global warming, especially male fertility. However, most studies on mating and reproductive performance have used as model organism polyandrous species, remaining unclear if and how will monandrous species respond. This is unfortunate as one could expect monandrous species to be particularly susceptible, given their inability to use sperm from multiple males to prevent reduced progeny production due to male sterility. It could be that monandrous females can overcome this toll in fertility by plastically changing their mating rate, or that monandrous populations evolve the ability to remate upon repeated exposure to heat. To test this, we studied the real-time evolution as well as the thermal plastic response of two geographically distinct populations of the monandrous species Drosophila subobscura after 45 generations evolving under a warming scenario. We assessed the impact of heat on male mating behaviour and fertility, as well as the impact of reduced male fertility on female mating behaviour and fertility. We found that in males the toll in mating behaviour due to heat can be recovered with time, whereas that in reproductive success cannot. On the other hand, females exposed to heat-stressed males significantly increased their remating rate, allowing to recover considerably their own reproductive success. Interestingly, most responses were plastic, with no striking effect of adaptation to warming nor of geographical origin. Our work brings new insights into the effects of heat on monandrous species and establishes a model to study how a shift in mating system may affect species ability to respond to climate change.

evolutionary biology↗

bioRxiv2023

Humoral and T-cell-mediated responses to a pre-clinical Zika vaccine candidate that utilizes a unique insect-specific flavivirus platform

Vaccination is critical for the control and prevention of viral outbreaks, yet conventional vaccine platforms may involve trade-offs between immunogenicity and safety. Insect-specific viruses have emerged as a novel vaccine platform to overcome this challenge. Detailed studies of humoral and T-cell responses induced by new insect-specific flavivirus (ISFV)-based vaccine platforms are needed to better understand correlates of protection and improve vaccine efficacy. Previously, we used a novel ISFV called Aripo virus (ARPV) to create a Zika virus (ZIKV) vaccine candidate (designated ARPV/ZIKV). ARPV/ZIKV demonstrated exceptional safety and single-dose efficacy, completely protecting mice from a lethal ZIKV challenge. Here, we explore the development of immune responses induced by ARPV/ZIKV immunization and evaluate its correlates of protection. Passive transfer of ARPV/ZIKV-induced immune sera to naive mice prior to challenge emphasized the importance of neutralizing antibodies as a correlate of protection. Depletion of T-cells in vaccinated mice and adoptive transfer of ARPV/ZIKV-primed T-cells to naive mice prior to challenge indicated that ARPV/ZIKV-induced CD4+ and CD8+ T-cell responses contribute to the observed protection but may not be essential for protection during ZIKV challenge. However, vaccination of Rag1 KO, Tcra KO, and muMt- mice demonstrated the critical role for ARPV/ZIKV-induced T-cells in developing protective immune responses following vaccination. Overall, both humoral and T-cell-mediated responses induced by ISFV-based vaccines are important for comprehensive immunity, and ISFV platforms continue to be a promising method for future vaccine development.

microbiology↗

bioRxiv2022

GSK-3484862 targets DNMT1 for degradation in cells

Maintenance of genomic methylation patterns at DNA replication forks by DNMT1 is the key to faithful mitotic inheritance. DNMT1 is often overexpressed in cancer cells and the DNA hypomethylating agents azacytidine and decitabine are currently used in the treatment of hematologic malignancies. However, the toxicity of these cytidine analogs and their ineffectiveness in treating solid tumors have limited wider clinical use. GSK-3484862 is a newly-developed, dicyanopyridine containing, non-nucleoside DNMT1-selective inhibitor with low cellular toxicity. Here, we show that GSK-3484862 targets DNMT1 for protein degradation in both cancer cell lines and murine embryonic stem cells (mESCs). DNMT1 depletion was rapid, taking effect within hours following GSK-3484862 treatment, leading to global hypomethylation. Inhibitor-induced DNMT1 degradation was proteasome-dependent, with no discernible loss of DNMT1 mRNA. In mESCs, GSK-3484862-induced Dnmt1 degradation requires Uhrf1, an accessory factor of Dnmt1 with E3 ubiquitin ligase activity. We also show that Dnmt1 depletion and DNA hypomethylation induced by the compound are reversible after its removal. Together, these results indicate that this DNMT1-selective degrader/inhibitor will be a valuable tool for dissecting both coordinated events linking DNA methylation to gene expression and identifying downstream effectors that ultimately regulate cellular response to altered DNA methylation patterns in a tissue/cell-specific manner. HighlightsO_LIGSK-3484862 targets DNMT1 for protein degradation in a wide-range of cancer cell lines, without a decrease in DNMT1 mRNA levels C_LIO_LIDNMT1 depletion leads to a >50% loss of global DNA methylation in cells within 2-days of treatment with GSK-3484862 C_LIO_LIGSK-3484862-induced DNMT1 degradation is proteasome-dependent C_LIO_LIIn mESCs, Uhrf1 is required for GSK-3484862 to induce Dnmt1 degradation C_LI

cancer biology↗

bioRxiv2021

No evidence for short-term evolutionary response to a warming environment in Drosophila

Adaptive evolution is key in mediating responses to climate change. Such evolution will expectedly lead to changes in the populations thermal reaction norm and improve their ability to cope with stressful conditions. Conversely, constraints of different nature might limit the adaptive response. Here, we test these expectations by performing a real-time evolution experiment in historically differentiated Drosophila subobscura populations. We address the phenotypic changes of flies evolving for nine generations in a daily fluctuating environment with average constant temperature, or a warming environment with increasing average and amplitude temperature across generations. Our results showed that (1) evolution under a global warming scenario has not led, so far, to a noticeable change in the thermal response; (2) historical background appears to be affecting the responses of populations under the warming environment, particularly at higher temperatures; (3) thermal reaction norms are trait-dependent: while lifelong exposure to low temperature decreases fecundity and productivity but not viability, high temperature causes negative transgenerational effects on productivity and viability, even though fecundity remains high. These findings raise concerns about the short-term efficiency of adaptive responses to the current changing climate.

evolutionary biology↗

bioRxiv2020

High developmental temperature leads to low reproduction despite adult temperature

Phenotypic plasticity can be an important tool in helping organisms to cope with changing thermal conditions and it may show an interdependency between life-stages. For instance, exposure to stressful temperatures during development can trigger a positive plastic response in adults. In this study, we analyse the thermal plastic response of laboratory populations of Drosophila subobscura, derived from two contrasting latitudes of the European cline. We measured fecundity characters in the experimental populations after exposure to five thermal treatments, with different combinations of developmental and adult temperatures (14{degrees}C, 18{degrees}C or 26{degrees}C). We ask whether (1) adult performance is enhanced (or reduced) by exposing flies to higher (or lower) temperatures during development only; (2) flies raised at lower temperatures outperform those developed at higher ones, supporting the "colder is better" hypothesis; (3) there is a cumulative effect on adult performance of exposing both juveniles and adults to higher (or lower) temperatures; (4) there is any evidence for historical effects on adult performance. Our main findings show that (1) higher developmental temperatures led to low reproductive performance regardless of adult temperature, while at lower temperatures reduced performance only occurred when cold conditions were persistent across juvenile and adult stage; (2) flies raised at lower temperatures did not always outperform those developed at other temperatures; (3) there was no (negative) cumulative effect of exposing both juveniles and adults to higher temperatures; (4) both latitudinal populations showed similar thermal plasticity patterns. The negative effect of high developmental temperature on reproductive performance, regardless of adult temperature, highlights the developmental stage as a critical and most vulnerable stage to climate change and associated heat waves.

evolutionary biology↗

bioRxiv2019

How phenotypic convergence arises in experimental evolution

Evolutionary convergence is a core issue in the study of adaptive evolution, as well as a highly debated topic at present. Few studies have analyzed this issue using a \"real-time\" or evolutionary trajectory approach. Do populations that are initially differentiated converge to a similar adaptive state when experiencing a common novel environment? Drosophila subobscura populations founded from different locations and years showed initial differences and variation in evolutionary rates in several traits during short-term ([~]20 generations) laboratory adaptation. Here we extend that analysis to 40 more generations to analyze (1) how differences in evolutionary dynamics between populations change between shorter and longer time spans, and (2) whether evolutionary convergence occurs after sixty generations of evolution in a common environment. We found substantial variation in longer-term evolutionary trajectories and differences between short and longer-term evolutionary dynamics. Though we observed pervasive patterns of convergence towards the character values of long-established populations, populations still remain differentiated for several traits at the final generations analyzed. This pattern might involve transient divergence, as we report in some cases, indicating that more generations should lead to final convergence. These findings highlight the importance of longer-term studies for understanding convergent evolution.

evolutionary biology↗