Temporal stability and directional change in a color cline of a marine snail from NW Spain.

The evolution and maintenance of color clines is a classic topic of research in evolutionary ecology. However, studies analyzing the temporal dynamics of such clines are much less frequent, due to the difficulty of obtaining reliable data about past color distributions along environmental gradients. In this article, we describe a case of decades-long temporal stability and directional change in a color cline of the marine snail Littorina saxatilis along the coastal inlet of the Ría de Vigo (NW Spain). L. saxatilis from this area shows a clear color cline with 3 distinct areas from the innermost to the more wave-exposed localities of the Ría: the inner, protected localities show an abundance of fawn-like individuals; the intermediate localities show a high diversity of colors; and the outer, wave-exposed localities show populations with a high frequency of a black and lineated morph. We compare data from the 1970s and 2022 in the same localities, showing that the cline has kept relatively stable for at least over half a century, except for some directional change and local variability in the frequency of certain morphs. Multiple regression analyses and biodiversity measures are presented to provide clues into the selective pressures that might be involved in the maintenance of this color cline. Future research avenues to properly test the explanatory power of these selective agents as well as the possible origins of the cline are discussed.

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Hospital padrino: a collaborative strategy model to tackle maternal mortality: a mixed methods study in a middle-income region.

Background: Reducing maternal mortality ratio (MMR) remains a paramount goal for low- and middle-income countries (LMICs), especially after COVID-19's devastating impact on maternal health indicators. We describe our experience implementing the Hospital Padrino Strategy (HPS), a collaborative model between a high-complexity hospital (Fundación Valle del Lili) and 43 medium- and low-complexity hospitals in one Colombian department (an administrative and territorial division) from 2021 to 2022, to sustain the trend towards reducing MMR. The study aimed to assess the effects of implementing HPS on both hospital performance and maternal health indicators in Valle del Cauca department (VCD). Methods: A mixed-methods study was conducted, comprising two phases. In the first phase, we investigated a cohort of hospitals through prospective follow-up to assess the outcomes of HPS implementation on hospital performance and maternal health indicators in VCD. In the second phase, qualitative data were collected through focus groups with 131 health workers from 33 hospitals to explore the implications of the HPS implementation on healthcare personnel. All data were obtained from records within the HPS implementation and from the Health Secretary of VCD. Findings: Evidence shows that in the context of HPS, 51 workshops involved 980 healthcare workers, covering the entire territory. Substantial improvements were observed in hospital conditions and healthcare personnel's technical competencies when providing obstetric care. Seven hundred eighty-five pregnant women with obstetric or perinatal emergencies received care through telehealth systems, with a progressive increase in technology adoption. Nine percent required Intensive Care Unit (ICU) admission, and none died. The MMR decreased from 78.8 in 2021 to 12.0 cases per 100,000 live births by 2022. Improvements in indicators and conducted training sessions instilled confidence and empowerment among the healthcare teams in the sponsored hospitals, as evidenced in focus groups derived from a sample of 131 healthcare workers from 33 hospitals. Interpretation: Implementing the Hospital Padrino Strategy led to a significant MMR reduction, and consolidated a model of social healthcare innovation replicable in LMICs. Funding: The Hospital Padrino Strategy was funded by the Fundación Valle del Lili and the Health Secretary of Valle del Cauca. Furthermore, this study received funding from a general grant for research from Tecnoquimicas S.A.

One-step conservative surgery vs hysterectomy for placenta accreta spectrum: a feasibility randomized controlled trial.

BACKGROUND: Placenta accreta spectrum is a serious condition associated with significant maternal morbidity and even mortality. The recommended treatment is hysterectomy. An alternative is 1-step conservative surgery, which involves the en bloc resection of the myometrium affected by placenta accreta spectrum along with the placenta, followed by uterine reconstruction. Currently, there are no studies comparing the 2 techniques in the setting of a randomized controlled trial. OBJECTIVE: We performed a prospectively registered multicenter randomized controlled trial comparing hysterectomy with 1-step conservative surgery. The aim was to collect feasibility and clinical outcomes of the 2 techniques in women assigned to hysterectomy or 1-step conservative surgery. In addition to assessing participants' willingness to be randomized, we also collected data on intraoperative blood loss, transfusion requirement, serious adverse event, and other clinical outcomes. STUDY DESIGN: Sixty women with strong antenatal suspicion of placenta accreta spectrum were assigned randomly to either hysterectomy (n=31) or 1-step conservative surgery (n=29). RESULTS: During a 20-month period, 60 of the 64 eligible patients (93.7%) underwent randomization. Intention-to-treat analysis showed that the clinical outcomes for 1-step conservative surgery were comparable to those of hysterectomy (median intraoperative blood loss, 1740 mL [interquartile range, 1010-2410] vs 1500 mL [interquartile range, 1122-2753]; odds ratio, 1 [1-1]; P=.942; median duration of surgery, 135 minutes [interquartile range, 111-180] vs 155 minutes [interquartile range, 120-185]; odds ratio, 0.99 [0.98-1]; P=.151; transfusion rate, 58.6% vs 61.3%; odds ratio, 0.96 [0.83-1.76]; P=.768; and adverse event rate, 17.2% vs 9.7%; odds ratio, 1.77 [0.43-10.19]; P=.398; respectively). In the subgroup of women with type 1 class on topographic classification, all participants allocated to 1-step surgery had successful outcomes, which were superior to those of hysterectomy. This was evidenced by the shorter surgery duration (median, 125 [interquartile range, 98-128] vs 180 [129-226] minutes; P=.002), lower transfusion rates (46.2% vs 82.4%), and fewer units of red blood cells transfused (median, 1 [interquartile range, 1-1.8] vs 3 [interquartile range, 2-4] units; P=.007). CONCLUSION: A randomized controlled trial comparing 2 surgical techniques for the treatment of placenta accreta spectrum is feasible. One-step conservative repair is a valid alternative to hysterectomy in the large majority of cases, but this can only be ascertained following intraoperative surgical staging.

Virome Data Explorer: A web resource to longitudinally explore respiratory viral infections, their interactions with other pathogens and host transcriptomic changes in over 100 people.

Viral respiratory infections are an important public health concern due to their prevalence, transmissibility, and potential to cause serious disease. Disease severity is the product of several factors beyond the presence of the infectious agent, including specific host immune responses, host genetic makeup, and bacterial coinfections. To understand these interactions within natural infections, we designed a longitudinal cohort study actively surveilling respiratory viruses over the course of 19 months (2016 to 2018) in a diverse cohort in New York City. We integrated the molecular characterization of 800+ nasopharyngeal samples with clinical data from 104 participants. Transcriptomic data enabled the identification of respiratory pathogens in nasopharyngeal samples, the characterization of markers of immune response, the identification of signatures associated with symptom severity, individual viruses, and bacterial coinfections. Specific results include a rapid restoration of baseline conditions after infection, significant transcriptomic differences between symptomatic and asymptomatic infections, and qualitatively similar responses across different viruses. We created an interactive computational resource (Virome Data Explorer) to facilitate access to the data and visualization of analytical results.

Social determinants influencing cervical cancer diagnosis: an ecological study.

BACKGROUND: Barriers to accessing health care result in advanced cervical cancer. In Sao Paulo, Brazil, the Index of Social Responsibility (ISR) synthesizes the situation of each town concerning wealth, education, and longevity. This study aimed to evaluate in 645 municipalities the relation of the ISR with stage, age, and morphology in cervical cancer diagnosis. METHODS: An ecological study that used data from Sao Paulo, Brazil, from 2010 to 2017. The ISR was identified through government platforms and data on cancer through the Hospital Cancer Registry. The subjects were the 9,095 women aged 30 years or older. The ISR summarizes municipalities into five levels: dynamic (ISR5), unequal (ISR4), equitable (ISR3), in transition (ISR2), and vulnerable (ISR1). It was used the chi2 tests and logistic regression. RESULTS: The proportion of stage 1 increased significantly with ISR level, ranging from 24.9% in ISR1 to 30.0% in ISR5 (p = 0.040). To every increase in ISR level, the chance of a woman being diagnosed in stage I was at least 30% higher. Woman living where ISR2 had a 1.4 times higher chance of being diagnosed in stage 1 than those living in ISR1 (OR 1.40, 95% CI 1.07-1.84). Squamous tumors frequency decreased when ISR level increased (p = 0.117). A higher proportion of women under 50 years were observed when they lived in wealthier cities (ISR4 and ISR5) (42.2% vs. 44.6%, p = 0.016). CONCLUSION: The ISR was a good health indicator for understanding and predicting the social determinants in cervical cancer diagnosis. The proportion of stage I increased significantly in more favorable social conditions.

Shell color polymorphism in marine gastropods.

Marine gastropods are characterized by an incredible variation in shell color. In this review, we aim to introduce researchers to previous studies of shell color polymorphism in this group of animals, trying to provide an overview of the topic and highlighting some potential avenues for future research. For this, we tackle the different aspects of shell color polymorphism in marine gastropods: its biochemical and genetic basis, its patterns of spatial and temporal distribution, as well as its potential evolutionary causes. In particular, we put special emphasis on the evolutionary studies that have been conducted so far to reveal the evolutionary mechanisms responsible for the maintenance of shell color polymorphism in this group of animals, as it constitutes the least addressed aspect in existing literature reviews. Several general conclusions can be drawn from our review: First, natural selection is commonly involved in the maintenance of gastropod color polymorphism; second, although the contribution of neutral forces (gene flow-genetic drift equilibrium) to shell color polymorphism maintenance do not seem to be particularly important, it has rarely been studied systematically; third, a relationship between shell color polymorphism and mode of larval development (related to dispersal capability) may exist. As for future studies, we suggest that a combination of both classical laboratory crossing experiments and -Omics approaches may yield interesting results on the molecular basis of color polymorphism. We believe that understanding the various causes of shell color polymorphism in marine gastropods is of great importance not only to understand how biodiversity works, but also for protecting such biodiversity, as knowledge of its evolutionary causes may help implement conservation measures in those species or ecosystems that are threatened.

Thermodynamic effects drive countergradient responses in the thermal performance of Littorina saxatilis across latitude.

Thermal performance curves (TPCs) provide a powerful framework to assess the evolution of thermal sensitivity in populations exposed to divergent selection regimes across latitude. However, there is a lack of consensus regarding the extent to which physiological adjustments that compensate for latitudinal temperature variation (metabolic cold adaptation; MCA) may alter the shape of TPCs, including potential repercussion on upper thermal limits. To address this, we compared TPCs for cardiac activity in latitudinally-separated populations of the intertidal periwinkle Littorina saxatilis. We applied a non-linear TPC modelling approach to explore how different metrics governing the shape of TPCs varied systematically in response to local adaptation and thermal acclimation. Both critical upper limits, and the temperatures at which cardiac performance was maximised, were higher in the northernmost (cold-adapted) population and displayed a countergradient latitudinal trend which was most pronounced following acclimation to low temperatures. We interpret this response as a knock-on consequence of increased standard metabolic rate in high latitude populations, indicating that physiological compensation associated with MCA may indirectly influence variation in upper thermal limits across latitude. Our study highlights the danger of assuming that variation in any one aspect of the TPC is adaptive without appropriate mechanistic and ecological context.

Thoracic ultrasound alone or in combination with tracheal amylase as a tool predictor of ventilator-associated pneumonia in neurocritical patients.

In this study, we aim to evaluate whether thoracic ultrasound (TUS) and tracheal amylase (TA) alone or in combination can predict the development of ventilator-associated pneumonia (VAP) in neurocritical patients. Consecutive adult patients with neurocritical disease with normal chest radiographs who required intensive care unit admission and mechanical ventilation between March 2015 and July 2018 were included. TUS and Amylase levels were measured during the first 24 hours and repeated 48 hours after orotracheal intubation. Forty-three patients with a median age of 34 years (17-82) were included. TUS had a sensitivity of 100% and specificity of 96.3% as a predictor of VAP within the first 48 hours when nonpattern A was observed. TA levels > 200 UI/L in the first 48 hours had a sensitivity of 87.5%, and specificity of 63% as a predictor of VAP. Moreover, no benefit of TUS plus TA compared to TUS alone as a predictor of VAP was found. The identification of abnormal TUS patterns in the first 48 hours of orotracheal intubation is a significant predictor of VAP in neurocritical patients.

Proteomic analysis of F1 hybrids and intermediate variants in a Littorina saxatilis hybrid zone.

Proteomic analysis was carried out on the Crab (upper-shore) and Wave (lower-shore) ecotypes of Littorina saxatilis from a hybrid zone at Silleiro Cape, Spain. Proteome profiles of individual snails were obtained. Protein expression in F1 hybrid snails bred in the laboratory and snails with intermediate shell phenotypes collected from the mid-shore were compared with Crab and Wave ecotypes using analytical approaches used to study dominance. Multivariate analysis over many protein spots showed that the F1 snails are distinct from both ecotypes but closer to the Wave ecotype. The intermediate snails are highly variable, some closer to the Crab and others to the Wave ecotype. Considered on a protein by protein basis, some proteins are significantly closer in expression to the Crab and others to the Wave ecotype for both F1 and intermediate snails. Furthermore, a significant majority of proteins were closer in expression to the Wave ecotype for the F1, consistent with the multivariate analysis. No such significant majority toward either the Crab or Wave ecotype was observed for the intermediate snails. The closer similarity of F1 and Wave ecotype expression patterns could be the result of similar selective pressures in the similar mid-shore and low-shore environments. For a significantly larger number of proteins, intermediate snails were closer in expression to the ecotype having the lower expression, for both Crab and Wave ecotypes. This is somewhat unexpected as lower expression might be expected to be an indication of impairment of function and lower fitness. Proteomic analysis could be important for the identification of candidate proteins useful for gaining improved understanding of adaptation and barriers to gene flow in hybrid zones.

Nucleotide substitutions in the mexR, nalC and nalD regulator genes of the MexAB-OprM efflux pump are maintained in Pseudomonas aeruginosa genetic lineages.

Pseudomonas aeruginosa has different resistant mechanisms including the constitutive MexAB-OprM efflux pump. Single nucleotide polymorphisms (SNPs) in the mexR, nalC, and nalD repressors of this efflux pump can contribute to antimicrobial resistance; however, it is unknown whether these changes are mainly related to genetic lineages or environmental pressure. This study identifies SNPs in the mexR, nalC, and nalD genes in clinical and environmental isolates of P. aeruginosa (including high-risk clones). Ninety-one P. aeruginosa strains were classified according to their resistance to antibiotics, typified by multilocus sequencing, and mexR, nalC, and nalD genes sequenced for SNPs identification. The mexAB-oprM transcript expression was determined. The 96.7% of the strains were classified as multidrug resistant. Eight strains produced serine carbapenemases, and 11 strains metallo-ß-lactamases. Twenty-three new STs and high-risk clones ST111 and ST233 were identified. SNPs in the mexR, nalC, and nalD genes revealed 27 different haplotypes (patterns). Sixty-two mutational changes were identified, 13 non-synonymous. Haplotype 1 was the most frequent (n = 40), and mainly identified in strains ST1725 (33/40), with 57.5% pan drug resistant strains, 36.5% extensive drug resistant and two strains exhibiting serin-carbapenemases. Haplotype 12 (n = 9) was identified in ST233 and phylogenetically related STs, with 100% of the strains exhibiting XDR and 90% producing metallo-ß-lactamases. Haplotype 5 was highly associated with XDR and related to dead when compared to ST1725 and ST233 (RRR 23.34; p = 0.009 and RRR 32.01; p = 0.025). A significant relationship between the mexR-nalC-nalD haplotypes and phylogenetically related STs was observed, suggesting mutational changes in these repressors are highly maintained within genetic lineages. In addition, phylogenetically related STs showed similar resistant profiles; however, the resistance was (likely or partly) attributed to the MexAB-OprM efflux pump in 56% of the strains (only 45.05% showed mexA overtranscription), in the remaining strains the resistance could be attributed to carbapenemases or mechanisms including other pumps, since same SNPs in the repressor genes gave rise to different resistance profiles.

Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T cell lymphoma.

Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) comprises heterogeneous lymphoid malignancies characterized by pleomorphic lymphocytes and variable inflammatory cell-rich tumor microenvironment. Genetic drivers in PTCL-NOS include genomic alterations affecting the VAV1 oncogene; however, their specific role and mechanisms in PTCL-NOS remain incompletely understood. Here we show that expression of Vav1-Myo1f, a recurrent PTCL-associated VAV1 fusion, induces oncogenic transformation of CD4+ T cells. Notably, mouse Vav1-Myo1f lymphomas show T helper type 2 features analogous to high-risk GATA3+ human PTCL. Single-cell transcriptome analysis reveals that Vav1-Myo1f alters T cell differentiation and leads to accumulation of tumor-associated macrophages (TAMs) in the tumor microenvironment, a feature linked with aggressiveness in human PTCL. Importantly, therapeutic targeting of TAMs induces strong anti-lymphoma effects, highlighting the lymphoma cells' dependency on the microenvironment. These results demonstrate an oncogenic role for Vav1-Myo1f in the pathogenesis of PTCL, involving deregulation in T cell polarization, and identify the lymphoma-associated macrophage-tumor microenvironment as a therapeutic target in PTCL.

Comparative Venomics of the Cryptic Cone Snail Species Virroconus ebraeus and Virroconus judaeus.

The venom duct transcriptomes and proteomes of the cryptic cone snail species Virroconus ebraeus and Virroconus judaeus were obtained and compared. The most abundant and shared conotoxin precursor superfamilies in both species were M, O1, and O2. Additionally, three new putative conotoxin precursor superfamilies (Virro01-03) with cysteine pattern types VI/VII and XVI were identified. The most expressed conotoxin precursor superfamilies were SF-mi2 and M in V. ebraeus, and Cerm03 and M in V. judaeus. Up to 16 conotoxin precursor superfamilies and hormones were differentially expressed between both species, and clustered into two distinct sets, which could represent adaptations of each species to different diets. Finally, we predicted, with machine learning algorithms, the 3D structure model of selected venom proteins including the differentially expressed Cerm03 and SF-mi2, an insulin type 3, a Gastridium geographus GVIA-like conotoxin, and an ortholog to the Pionoconus magus ω-conotoxin MVIIA (Ziconotide).

Role of Helicobacter pylori and Other Environmental Factors in the Development of Gastric Dysbiosis.

Microbiomes are defined as complex microbial communities, which are mainly composed of bacteria, fungi, and viruses residing in diverse regions of the human body. The human stomach consists of a unique and heterogeneous habitat of microbial communities owing to its anatomical and functional characteristics, that allow the optimal growth of characteristic bacteria in this environment. Gastric dysbiosis, which is defined as compositional and functional alterations of the gastric microbiota, can be induced by multiple environmental factors, such as age, diet, multiple antibiotic therapies, proton pump inhibitor abuse, H. pylori status, among others. Although H. pylori colonization has been reported across the world, chronic H. pylori infection may lead to serious consequences; therefore, the infection must be treated. Multiple antibiotic therapy improvements are not always successful because of the lack of adherence to the prescribed antibiotic treatment. However, the abuse of eradication treatments can generate gastric dysbiotic states. Dysbiosis of the gastric microenvironment induces microbial resilience, due to the loss of relevant commensal bacteria and simultaneous colonization by other pathobiont bacteria, which can generate metabolic and physiological changes or even initiate and develop other gastric disorders by non-H. pylori bacteria. This systematic review opens a discussion on the effects of multiple environmental factors on gastric microbial communities.

Recombination and lineage-specific mutations linked to the emergence of SARS-CoV-2.

BACKGROUND: The emergence of SARS-CoV-2 underscores the need to better understand the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. In the betacoronavirus genus, which also includes SARS-CoV and MERS-CoV, recombination frequently encompasses the receptor binding domain (RBD) of the Spike protein, which is responsible for viral binding to host cell receptors. In this work, we reconstruct the evolutionary events that have accompanied the emergence of SARS-CoV-2, with a special emphasis on the RBD and its adaptation for binding to its receptor, human ACE2. METHODS: By means of phylogenetic and recombination analyses, we found evidence of a recombination event in the RBD involving ancestral linages to both SARS-CoV and SARS-CoV-2. We then assessed the effect of this recombination at protein level by reconstructing the RBD of the closest ancestors to SARS-CoV-2, SARS-CoV, and other Sarbecoviruses, including the most recent common ancestor of the recombining clade. The resulting information was used to measure and compare, in silico, their ACE2-binding affinities using the physics-based trRosetta algorithm. RESULTS: We show that, through an ancestral recombination event, SARS-CoV and SARS-CoV-2 share an RBD sequence that includes two insertions (positions 432-436 and 460-472), as well as the variants 427N and 436Y. Both 427N and 436Y belong to a helix that interacts directly with the human ACE2 (hACE2) receptor. Reconstruction of ancestral states, combined with protein-binding affinity analyses, suggests that the recombination event involving ancestral strains of SARS-CoV and SARS-CoV-2 led to an increased affinity for hACE2 binding and that alleles 427N and 436Y significantly enhanced affinity as well. CONCLUSIONS: We report an ancestral recombination event affecting the RBD of both SARS-CoV and SARS-CoV-2 that was associated with an increased binding affinity to hACE2. Structural modeling indicates that ancestors of SARS-CoV-2 may have acquired the ability to infect humans decades ago. The binding affinity with the human receptor would have been subsequently boosted in SARS-CoV and SARS-CoV-2 through further mutations in RBD.

Divergence in Thermal Physiology Could Contribute to Vertical Segregation in Intertidal Ecotypes of Littorina saxatilis.

AbstractThermal stress is a potentially important selective agent in intertidal marine habitats, but the role that thermal tolerance might play in local adaptation across shore height has been underexplored. Northwest Spain is home to two morphologically distinct ecotypes of the periwinkle Littorina saxatilis, separated by shore height and subject to substantial differences in thermal stress exposure. However, despite other biotic and abiotic drivers of ecotype segregation being well studied, their thermal tolerance has not been previously characterized. We investigated thermal tolerance across multiple life history stages by employing the thermal death time (TDT) approach to determine (i) whether the two ecotypes differ in thermal tolerance and (ii) how any differences vary with life history stage. Adults of the two ecotypes differed in their thermal tolerance in line with their shore position: the upper-shore ecotype, which experiences more extreme temperatures, exhibited greater endurance of thermal stress compared with the lower-shore ecotype. This difference was most pronounced at the highest temperatures tested. The proximate physiological basis for these differences is unknown but likely due to a multifarious interaction of traits affecting different parts of the TDT curve. Differences in tolerance between ecotypes were less pronounced in early life history stages but increased with ontogeny, suggesting partial divergence of this trait during development. Thermal tolerance could potentially play an important role in maintaining population divergence and genetic segregation between the two ecotypes, since the increased thermal sensitivity of the lower-shore ecotype may limit its dispersal onto the upper shore and so restrict gene flow.

Negative frequency-dependent selection maintains shell banding polymorphisms in two marine snails (Littorina fabalis and Littorina saxatilis).

The presence of shell bands is common in gastropods. Both the marine snails Littorina fabalis and Lttorina saxatilis are polymorphic for this trait. Such polymorphism would be expected to be lost by the action of genetic drift or directional selection, but it appears to be widespread at relatively constant frequencies. This suggests it is maintained by balancing selection on the trait or on a genetically linked trait. Using long time series of empirical data, we compared potential effects of genetic drift and negative frequency-dependent selection (NFDS) in the two species. The contribution of genetic drift to changes in the frequency of bands in L. fabalis was estimated using the effective population size estimated from microsatellite data, while the effect of genetic drift in L. saxatilis was derived from previously published study. Frequency-dependent selection was assessed by comparing the cross-product estimator of fitness with the frequency of the polymorphism across years using a regression analysis. Both studied species showed patterns of NFDS. In addition, in L. fabalis, contributions from genetic drift could explain some of the changes in banding frequency. Overdominance and heterogeneous selection did not fit well to our data. The possible biological explanations resulting in the maintenance of the banding polymorphism are discussed.

Global Patterns of Recombination across Human Viruses.

Viral recombination is a major evolutionary mechanism driving adaptation processes, such as the ability of host-switching. Understanding global patterns of recombination could help to identify underlying mechanisms and to evaluate the potential risks of rapid adaptation. Conventional approaches (e.g., those based on linkage disequilibrium) are computationally demanding or even intractable when sequence alignments include hundreds of sequences, common in viral data sets. We present a comprehensive analysis of recombination across 30 genomic alignments from viruses infecting humans. In order to scale the analysis and avoid the computational limitations of conventional approaches, we apply newly developed topological data analysis methods able to infer recombination rates for large data sets. We show that viruses, such as ZEBOV and MARV, consistently displayed low levels of recombination, whereas high levels of recombination were observed in Sarbecoviruses, HBV, HEV, Rhinovirus A, and HIV. We observe that recombination is more common in positive single-stranded RNA viruses than in negatively single-stranded RNA ones. Interestingly, the comparison across multiple viruses suggests an inverse correlation between genome length and recombination rate. Positional analyses of recombination breakpoints along viral genomes, combined with our approach, detected at least 39 nonuniform patterns of recombination (i.e., cold or hotspots) in 18 viral groups. Among these, noteworthy hotspots are found in MERS-CoV and Sarbecoviruses (at spike, Nucleocapsid and ORF8). In summary, we have developed a fast pipeline to measure recombination that, combined with other approaches, has allowed us to find both common and lineage-specific patterns of recombination among viruses with potential relevance in viral adaptation.

Genetic and morphological divergence between Littorina fabalis ecotypes in Northern Europe.

Low dispersal marine intertidal species facing strong divergent selective pressures associated with steep environmental gradients have a great potential to inform us about local adaptation and reproductive isolation. Among these, gastropods of the genus Littorina offer a unique system to study parallel phenotypic divergence resulting from adaptation to different habitats related with wave exposure. In this study, we focused on two Littorina fabalis ecotypes from Northern European shores and compared patterns of habitat-related phenotypic and genetic divergence across three different geographic levels (local, regional and global). Geometric morphometric analyses revealed that individuals from habitats moderately exposed to waves usually present a larger shell size with a wider aperture than those from sheltered habitats. The phenotypic clustering of L. fabalis by habitat across most locations (mainly in terms of shell size) support an important role of ecology in morphological divergence. A genome scan based on amplified fragment length polymorphisms (AFLPs) revealed a heterogeneous pattern of differentiation across the genome between populations from the two different habitats, suggesting ecotype divergence in the presence of gene flow. The contrasting patterns of genetic structure between nonoutlier and outlier loci, and the decreased sharing of outlier loci with geographic distance among locations are compatible with parallel evolution of phenotypic divergence, with an important contribution of gene flow and/or ancestral variation. In the future, model-based inference studies based on sequence data across the entire genome will help unravelling these evolutionary hypotheses, improving our knowledge about adaptation and its influence on diversification within the marine realm.

Recombination and lineage-specific mutations linked to the emergence of SARS-CoV-2.

The emergence of SARS-CoV-2 underscores the need to better understand the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. In the betacoronavirus genus, which also includes SARS-CoV and MERS-CoV, recombination frequently encompasses the Receptor Binding Domain (RBD) of the Spike protein, which, in turn, is responsible for viral binding to host cell receptors. Here, we find evidence of a recombination event in the RBD involving ancestral linages to both SARS-CoV and SARS-CoV-2. Although we cannot specify the recombinant nor the parental strains, likely due to the ancestry of the event and potential undersampling, our statistical analyses in the space of phylogenetic trees support such an ancestral recombination. Consequently, SARS-CoV and SARS-CoV-2 share an RBD sequence that includes two insertions (positions 432-436 and 460-472), as well as the variants 427N and 436Y. Both 427N and 436Y belong to a helix that interacts directly with the human ACE2 (hACE2) receptor. Reconstruction of ancestral states, combined with protein-binding affinity analyses using the physics-based trRosetta algorithm, reveal that the recombination event involving ancestral strains of SARS-CoV and SARS-CoV-2 led to an increased affinity for hACE2 binding, and that alleles 427N and 436Y significantly enhanced affinity as well. Structural modeling indicates that ancestors of SARS-CoV-2 may have acquired the ability to infect humans decades ago. The binding affinity with the human receptor was subsequently boosted in SARS-CoV and SARS-CoV-2 through further mutations in RBD. In sum, we report an ancestral recombination event affecting the RBD of both SARS-CoV and SARS-CoV-2 that was associated with an increased binding affinity to hACE2.