Independent acquisition of short insertions at the RIR1 site in the spike N-terminal domain of the SARS-CoV-2 BA.2 lineage

Although the major SARS-CoV-2 omicron lineages share over 30 non-synonymous substitutions in the spike glycoprotein, they show several unique mutations that were acquired after their ancestral split. One of the most intriguing mutations associated with BA.1 is the presence of the inserted tripeptide Glu-Pro-Glu within the N-terminal domain, at a site that had previously independently acquired short insertions in several other SARS-CoV-2 lineages. Although the functional implications of the small nucleotide sequences found at this insertion hotspot, named RIR1, are still unclear, we have previously hypothesized that they may play a compensatory role in counterbalancing minor fitness deficits associated with other co-occurring spike non-synonymous mutations. Here, we show that similar insertion events have independently occurred at RIR1 at least 20 times in early 2022 within the BA.2 lineage, being occasionally associated with significant community transmission. One of these omicron sublineages, characterized by a Ser-Gly-Arg insertion in position 212, has been responsible for over 4000 documented COVID-19 cases worldwide between January and July 2022, for the most part concentrated in Denmark, where it reached a national prevalence close to 4% (10% in the Nordjylland region) in mid-May. Although the concurrent spread of the BA.2.12.1, BA.4 and BA.5 lineages led to the rapid decline of this BA.2 sublineage, the independent acquisition of several other RIR1 insertions on a BA.2 genomic background suggests that these events may provide a slight fitness advantage. Therefore, they should be carefully monitored in the upcoming months in other emerging omicron-related lineages, including BA.5

Extensive Tandem Duplication Events Drive the Expansion of the C1q-Domain-Containing Gene Family in Bivalves

C1q-domain-containing (C1qDC) proteins are rapidly emerging as key players in the innate immune response of bivalve mollusks. Growing experimental evidence suggests that these highly abundant secretory proteins are involved in the recognition of microbe-associated molecular patterns, serving as lectin-like molecules in the bivalve proto-complement system. While a large amount of functional data concerning the binding specificity of the globular head C1q domain and on the regulation of these molecules in response to infection are quickly accumulating, the genetic mechanisms that have led to the extraordinary lineage-specific expansion of the C1qDC gene family in bivalves are still largely unknown. The analysis of the chromosome-scale genome assembly of the Eastern oyster Crassostrea virginica revealed that the 476 oyster C1qDC genes, far from being uniformly distributed along the genome, are located in large clusters of tandemly duplicated paralogs, mostly found on chromosomes 7 and 8. Our observations point out that the evolutionary process behind the development of a large arsenal of C1qDC lectin-like molecules in marine bivalves is still ongoing and likely based on an unequal crossing over

Molecular Diversity of Mytilin-Like Defense Peptides in Mytilidae (Mollusca, Bivalvia)

The CS-\u3b1\u3b2 architecture is a structural scaffold shared by a high number of small, cationic, cysteine-rich defense peptides, found in nearly all the major branches of the tree of life. Although several CS-\u3b1\u3b2 peptides involved in innate immune response have been described so far in bivalve mollusks, a clear-cut definition of their molecular diversity is still lacking, leaving the evolutionary relationship among defensins, mytilins, myticins and other structurally similar antimicrobial peptides still unclear. In this study, we performed a comprehensive bioinformatic screening of the genomes and transcriptomes available for marine mussels (Mytilida), redefining the distribution of mytilin-like CS-\u3b1\u3b2 peptides, which in spite of limited primary sequence similarity maintain in all cases a well-conserved backbone, stabilized by four disulfide bonds. Variations in the size of the alpha-helix and the two antiparallel beta strand region, as well as the positioning of the cysteine residues involved in the formation of the C1\u2013C5 disulfide bond might allow a certain degree of structural flexibility, whose functional implications remain to be investigated. The identification of mytilins in Trichomya and Perna spp. revealed that many additional CS-\u3b1\u3b2 AMPs remain to be formally described and functionally characterized in Mytilidae, and suggest that a more robust scheme should be used for the future classification of such peptides with respect with their evolutionary origi

I principi etico-esistenziali di Cosimo De Giorgi: un messaggio per la vita rivolto ai giovani

EnCosimo De Giorgi can be considered a man of our time, who conveys an important ethical and existential message to young people: the unity and specialization of knowledge, the dissemination and practical application of discoveries, the commitment to social progress, the moral value of education and work are extraordinary lessons for dealing with the crisis of values.ItCosimo De Giorgi può essere considerato un uomo del nostro tempo, che trasmette un importante messaggio etico ed esistenziale ai giovani: l'unità e la specializzazione del sapere, la divulgazione e l'applicazione pratica delle scoperte, l'impegno per il progresso sociale, il valore morale dell'educazione e del lavoro sono straordinari insegnamenti per affrontare la crisi dei valori

Unveiling the Impact of Gene Presence/Absence Variation in Driving Inter-Individual Sequence Diversity within the CRP-I Gene Family in Mytilus spp

Mussels (Mytilus spp.) tolerate infections much better than other species living in the same marine coastal environment thanks to a highly efficient innate immune system, which exploits a remarkable diversification of effector molecules involved in mucosal and humoral responses. Among these, antimicrobial peptides (AMPs) are subjected to massive gene presence/absence variation (PAV), endowing each individual with a potentially unique repertoire of defense molecules. The unavailability of a chromosome-scale assembly has so far prevented a comprehensive evaluation of the genomic arrangement of AMP-encoding loci, preventing an accurate ascertainment of the orthology/paralogy relationships among sequence variants. Here, we characterized the CRP-I gene cluster in the blue mussel Mytilus edulis, which includes about 50 paralogous genes and pseudogenes, mostly packed in a small genomic region within chromosome 5. We further reported the occurrence of widespread PAV within this family in the Mytilus species complex and provided evidence that CRP-I peptides likely adopt a knottin fold. We functionally characterized the synthetic peptide sCRP-I H1, assessing the presence of biological activities consistent with other knottins, revealing that mussel CRP-I peptides are unlikely to act as antimicrobial agents or protease inhibitors, even though they may be used as defense molecules against infections from eukaryotic parasites

Gene Expression Profiling of Trematomus bernacchii in Response to Thermal and Stabling Stress

The Antarctic continent is one of the most pristine environments on planet Earth, yet one of the most fragile and susceptible to the effects of the ongoing climate change. The overwhelming majority of the components of Antarctic marine trophic chain are stenotherm organisms, highly adapted to the extreme, but extremely stable, freezing temperatures of the Antarctic ocean, which have not changed significantly during the past fifteen million years. Notothenioid fishes are the most abundant representatives of ichthyofauna at these latitudes, being ubiquitously found in coastal areas across the entire continent. While different Antarctic fish species have been previously subjected to studies aimed at defining their range of thermal tolerance, or at studying the response to acute thermal stress, just a handful of authors have investigated the effects of the exposure to a moderate increase of temperature, falling within the expected forecasts for the next few decades in some areas of the Antarctica. Here, the emerald rockcod Trematomus bernacchii was used as a model species to investigate the effects of a 20-day long exposure to a +1.5 °C increase in the brain, gills and skeletal muscle, using a RNA-sequencing approach. In parallel, the experimental design also allowed for assessing the impact of stabling (including acclimation, the handling of fishes and their confinement in tanks during the experimental phase) on gene expression profiling. The results of this study clearly identified the brain as the most susceptible tissue to heat stress, with evidence of a time-dependent response dominated by an alteration of immune response, protein synthesis and folding, and energy metabolism-related genes. While the gills displayed smaller but still significant alterations, the skeletal muscle was completely unaffected by the experimental conditions. The stabling conditions also had an important impact on gene expression profiles in the brain, suggesting the presence of significant alterations of the fish nervous system, possibly due to the confinement to tanks with limited water volume and of the restricted possibility of movement. Besides providing novel insights in the molecular mechanisms underlying thermal stress in notothenioids, these findings suggest that more attention should be dedicated to an improved design of the experiments carried out on Antarctic organism, due to their extreme susceptibility to the slightest environmental alterations

Relaxation of natural selection in the evolution of the giant lungfish genomes

Nonadaptive hypotheses on the evolution of eukaryotic genome size predict an expansion when the process of purifying selection becomes weak. Accordingly, species with huge genomes, such as lungfish, are expected to show a genome-wide relaxation signature of selection compared with other organisms. However, few studies have empirically tested this prediction using genomic data in a comparative framework. Here, we show that 1) the newly assembled transcriptome of the Australian lungfish, Neoceratodus forsteri, is characterized by an excess of pervasive transcription, or transcriptional leakage, possibly due to suboptimal transcriptional control, and 2) a significant relaxation signature in coding genes in lungfish species compared with other vertebrates. Based on these observations, we propose that the largest known animal genomes evolved in a nearly neutral scenario where genome expansion is less efficiently constraine

Towards a Muon Collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.Comment: 118 pages, 103 figure

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work