Lineage replacement and evolution captured by the United Kingdom Covid Infection Survey

The Office for National Statistics COVID-19 Infection Survey is a large household-based surveillance study based in the United Kingdom. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing sequenced samples collected up until 13th November 2021. We observed four distinct sweeps or partial-sweeps, by lineages B.1.177, B.1.1.7/Alpha, B.1.617.2/Delta, and finally AY.4.2, a sublineage of B.1.617.2, with each sweeping lineage having a distinct growth advantage compared to their predecessors. Evolution was characterised by steady rates of evolution and increasing diversity within lineages, but with step increases in divergence associated with each sweeping major lineage, leading to a faster overall rate of evolution and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly as routine PCR testing is phased out or in settings where large-scale sequencing is not feasible.

A genomics dissection of Kenya’s COVID-19 waves: temporal lineage replacements and dominance of imported variants of concern

Kenya’s COVID-19 epidemic was slow to peak. It was seeded early in March 2020, and did not peak until late-July 2020 (wave 1), mid-November 2020 (wave 2) and late-March 2021 (wave 3). Here we present SARS-CoV-2 lineages associated with the three COVID-19 waves through analysis of 483 genomes, which included 167 Alpha (B.1.1.7), 57 Delta (B.1.617.2) and 12 Beta (B.1.351) variants of concerns (VOC) that dominated the third wave. In total, 35 lineages were identified. The early European lineages B.1 and B.1.1 were the first to be seeded in Kenya. The B.1 lineage continued to expand and remained the most dominant lineage accounting for 55.8% and 56.3% in waves 1 and 2 respectively. The alpha (B.1.1.7), delta (B.1.167.2) and beta (B.1.351) VOCs dominated in wave 3 at 59.0%, 20.1% and 4.2% respectively. Eventually, the delta variant took over at the tail end of wave 3 and at the time of going to press, it had become the major lineage in the whole country. Phylogenetic analysis suggested multiple introductions of variants from outside Kenya especially during the first and third wave. Phylogeny also highlighted local lineage diversification as local transmission events supervened. The data highlights the importance of genome surveillance in determining circulating variants to aid in public health interventions.

Geographical Prevalence of SARS-CoV-2 Variants, August 2020 to July 2021.

Coronavirus disease 2019 (COVID-19) pandemic has progressed into second year. The etiologic agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages, some of which are gifted with transmissibility advantages. This underscores the importance of variant surveillance, to keep public health countermeasures and our understanding on the virus up-to-date. In the light of this, we extracted one-year genomic data (August 2020 to July 2021) from Global Initiative on Sharing All Influenza Data (GISAID) EpiCoV™ database and estimated monthly proportions of 11 SARS-CoV-2 variants in various geographical regions. From continental perspective, delta variant of concern (VOC) predominated in Africa, Asia, Europe, North America and Oceania, with proportions ranging from 67.58 to 98.31% in July 2021. In South America, proportion of the expanding delta VOC (23.24%) has been getting closer to the predominant yet diminishing gamma VOC (56.86%). We further analyzed monthly data on new COVID-19 cases, new deaths, vaccination status and variant proportions of 6 countries. Similar to continental data, delta VOC predominated in all countries except Brazil in July 2021. In most occasions, rise and predominance of alpha, beta, gamma, delta and zeta variants were accompanied with surges of new cases, especially after the time points of major lineage interchange. The ascending phases of new cases lasted for 1 to 5 months with 1.69- to 40.63-fold peak growth, whereas new death toll varied with regional vaccination status. Our data suggested surges of COVID-19 cases might be predicted from variant surveillance data. Despite vaccine breakthroughs by delta VOC, death tolls were more stable in countries with better immunization coverage. Another takeaway is the urgent need to improve vaccine efficacy against delta and emerging variants.

Identification of PAX6 and NFAT4 as the transcriptional regulators of lncRNA Mrhl in neuronal progenitors

LncRNA Mrhlhas been shown to be involved in regulating meiotic commitment of mouse spermatogonial progenitors and coordinating differentiation events in mouse embryonic stem cells. Here we have characterized the interplay of Mrhlwith lineage-specific transcription factors during mouse neuronal lineage development. Our results demonstrate that Mrhl is predominantly expressed in the neuronal progenitor populations in mouse embryonic brains and in retinoic acid derived radial-glia like neuronal progenitor cells. Mrhl levels are significantly down regulated in postnatal brains and in maturing neurons. In neuronal progenitors, a master transcription factor, PAX6, acts to regulate the expression of Mrhl through direct physical binding at a major site in the distal promoter, located at 2.9kb usptream of the TSS of Mrhl. Furthermore, NFAT4 occupies the Mrhl proximal promoter at two sites, at 437bp and 143bp upstream of the TSS. ChIP studies reveal that PAX6 and NFAT4 interact with each other, suggesting co-regulation of lncRNA Mrhl expression in neuronal progenitors. Our studies herewith are crucial towards understanding how lncRNAs are regulated by major lineage-specific TFstowardsdefining specific development and differentiation events.

The Central Rituals

Chapter 3 shifts from Nechung’s mythological foundations to explore the monastery’s central rites. The three ritual manuals examined in this chapter are at the root of Nechung’s practices and illustrate a vivid ritual accretion over several centuries involving major lineage masters. Specifically, the core rite of Nechung composed by the Fifth Dalai Lama was developed and built up over lifetimes before culminating in the text it is today. The chapter ends by taking a closer look at the deity Dorjé Drakden, a minor emanation of Pehar with humble beginnings, whose importance grows to challenge and overtake even the centrality of the Five King Spirits. The final discussion on ritual reverberation has implications for the wider liturgical activities practiced by Nechung and shared with other institutions.

Investigation on Anthrax in Bangladesh during the Outbreaks of 2011 and Definition of the Epidemiological Correlations

In 2011, in Bangladesh, 11 anthrax outbreaks occurred in six districts of the country. Different types of samples were collected from May to September in the six districts where anthrax had occurred in order to detect and type Bacillus anthracis (B. anthracis) strains. Anthrax was detected in 46.6% of the samples analysed, in particular in soils, but also in bone samples, water, animal feed, and rumen ingesta of dead animals. Canonical single nucleotide polymorphisms (CanSNPs) analysis showed that all the isolates belonged to the major lineage A, sublineage A.Br.001/002 of China and Southeast Asia while the multi-locus variable number of tandem repeats (VNTRs) analysis (MLVA) with 15 VNTRs demonstrated the presence of five genotypes, of which two resulted to be new genotypes. The single nucleotide repeats (SNRs) analysis showed 13 SNR types; nevertheless, due to its higher discriminatory power, the presence of two isolates with different SNR-type polymorphisms was detected within two MLVA genotypes. This study assumes that soil is not the only reason for the spread of the disease in Bangladesh; contaminated feed and water can also play an important role in the epidemiology of anthrax. Possible explanations for these epidemiological relationships are discussed.

A Sister Lineage of Sampled Retroviruses Corroborates the Complex Evolution of Retroviruses

The origin and deep history of retroviruses remain mysterious and contentious, largely because the diversity of retroviruses is incompletely understood. Here, we report the discovery of lokiretroviruses, a novel major lineage of retroviruses, within the genomes of a wide range of vertebrates (at least 137 species), including lampreys, ray-finned fishes, lobe-finned fishes, amphibians, and reptiles. Lokiretroviruses share a similar genome architecture with known retroviruses, but display some unique features. Interestingly, lokiretrovirus Env proteins share detectable similarity with fusion glycoproteins of viruses within the Mononegavirales order, blurring the boundary between retroviruses and negative sense single-stranded RNA viruses. Phylogenetic analyses based on reverse transcriptase demonstrate that lokiretroviruses are sister to all the retroviruses sampled to date, providing a crucial nexus for studying the deep history of retroviruses. Comparing congruence between host and virus phylogenies suggests lokiretroviruses mainly underwent cross-species transmission. Moreover, we find that retroviruses replaced their ribonuclease H and integrase domains multiple times during their evolutionary course, revealing the importance of domain shuffling in the evolution of retroviruses. Overall, our findings greatly expand our views of the diversity of retroviruses, and provide novel insights into the origin and complex evolutionary history of retroviruses.

Gene duplication drives genome expansion in a major lineage of Thaumarchaeota

Ammonia-oxidising archaea of the phylum Thaumarchaeota are important organisms in the nitrogen cycle, but the mechanisms driving their radiation into diverse ecosystems remain underexplored. Here, existing thaumarchaeotal genomes are complemented with 12 genomes belonging to the previously under-sampled Nitrososphaerales to investigate the impact of lateral gene transfer (LGT), gene duplication and loss across thaumarchaeotal evolution. We reveal a major role for gene duplication in driving genome expansion subsequent to early LGT. In particular, two large LGT events are identified into Nitrososphaerales and the fate of these gene families is highly lineage-specific, being lost in some descendant lineages, but undergoing extensive duplication in others, suggesting niche-specific roles. Notably, some genes involved in carbohydrate transport or coenzyme metabolism were duplicated, likely facilitating niche specialisation in soils and sediments. Overall, our results suggest that LGT followed by gene duplication drives Nitrososphaerales evolution, highlighting a previously under-appreciated mechanism of genome expansion in archaea.

The evolution of feeding within Euchelicerata: data from the fossil groups Eurypterida and Trigonotarbida illustrate possible evolutionary pathways

When the evolution of Euarthropoda is discussed, often the lineage of Chelicerata s. str. is assumed to be the more ‘primitive’ or ‘basal’ part of the tree, especially when compared to the other major lineage, Mandibulata. This claimed primitiveness is (at least partly) based on the assumption that different morphological structures are still in an ancestral state and did not evolve any further. One of these sets of structures is the feeding apparatus, which has been stated to be highly advanced in Mandibulata, but not ‘properly’ developed, or at least not to such a high degree, within Chelicerata s. str. In this study, I reinvestigate the feeding apparatus of different ingroups of Euchelicerata, with a focus on assumed ‘primitive’ groups such as Eurypterida and Trigonotarbida. The basis of this study is a large amount of material from different museum collections, with fossils with the entire feeding apparatuses being exceptionally well preserved. Based on high-resolution micro-photography and three-dimensional imaging, it is possible to resolve fine details of the feeding apparatuses. The results make clear that the feeding apparatuses of different ingroups of Euchelicerata are highly specialised and often possess morphological structures comparable to those of the feeding apparatuses of representatives of Mandibulata, apparently convergently evolved. Though the reconstruction of the evolution of the feeding apparatus within Euchelicerata is to a certain degree hampered by unclear phylogenetic relationships, there was clearly a shortening of the feeding apparatus from posterior (i.e. only the anterior appendages being involved in the feeding apparatus), probably linked to the colonisation of land in Arachnida.

Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil

Despite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil.