Insights into the Epidemiology, Phylodynamics, and Evolutionary Changes of Lineage GI-7 Infectious Bronchitis Virus

Infectious bronchitis virus (IBV) is distributed worldwide and causes significant losses in the poultry industry. In recent decades, lineages GI-19 and GI-7 have become the most prevalent IBV strains in China. However, the molecular evolution and phylodynamics of the lineage GI-7 IBV strains remain largely unknown. In this study, we identified 19 IBV strains from clinical samples from January 2021 to June 2022 in China, including 12 strains of GI-19, 3 strains of GI-7, and 1 strain each of GI-1, GI-9, GI-13, and GI-28. These results indicated that lineages GI-19 and GI-7 IBVs are still the most prevalent IBVs in China. Here, we investigated the evolution and transmission dynamics of lineage GI-7 IBVs. Our results revealed that the Taiwan province might be the origin of lineage GI-7 IBVs and that South China plays an important role in the spread of IBV. Furthermore, we found low codon usage bias of the S1 gene in lineage GI-7 IBVs. This allowed IBV to replicate in the host during evolution as a result of reduced competition, mainly driven by natural selection and mutational pressure, where the role of natural selection is more prominent. Collectively, our results reveal the genetic diversity and evolutionary dynamics of lineage GI-7 IBVs, which could assist in the prevention and control of viral infection.

Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection.

Atherosclerosis is a systemic disease in which focal lesions in arteries promote the build-up of lipoproteins and cholesterol they are transporting. The development of atheroma (atherogenesis) narrows blood vessels, reduces the blood supply and leads to cardiovascular diseases. According to the World Health Organization (WHO), cardiovascular diseases are the leading cause of death, which has been especially boosted since the COVID-19 pandemic. There is a variety of contributors to atherosclerosis, including lifestyle factors and genetic predisposition. Antioxidant diets and recreational exercises act as atheroprotectors and can retard atherogenesis. The search for molecular markers of atherogenesis and atheroprotection for predictive, preventive and personalized medicine appears to be the most promising direction for the study of atherosclerosis. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection. The hub genes regulating these processes have been found to be the most ancient. In silico analysis of all 5112 SNPs in their promoters has revealed 330 candidate SNP markers, which statistically significantly change the affinity of the TATA-binding protein (TBP) for these promoters. These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection. At the same time, upregulation of the one for atheroprotection promotes human health.

Ongoing positive selection drives the evolution of SARS-CoV-2 genomes.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively through world populations since its first outbreak in December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving, and driven by adaptation to the new host and environments is still under debate. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30, 2021, we demonstrate with population genetic evidence that during the course of SARS-CoV-2 pandemic in humans, (i) SARS-CoV-2 genomes are overall conserved under purifying selection, especially for the 14 genes related to viral RNA replication, transcription, and assembly; (ii) Ongoing positive selection is actively driving the evolution of 6 genes (e.g., S, ORF3a, and N) that play critical roles in molecular processes involving pathogen-host interactions, including viral invasion into and egress from host cells, viral inhibition, or evasion of host immune response, possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution. According to an established haplotype phylogenetic relationship of 138 viral clusters, a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters, of which multiple mutations potentially conferring alterations in viral transmissibility, pathogenicity, and virulence of SARS-CoV-2 are highlighted, warranting attentions.

PHILOSOPHY, RELIGION, AND SCIENCE-Salafism and Biological Evolution: Online Salafi Reflections on the Theory of Evolution by Natural Selection

Gunter reviews Salafism and Biological Evolution: Online Salafi Reflections on the Theory of Evolution by Natural Selection, by Jean-Francois Letourneau.

Darwinism expunged from India's school textbooks

Speed read Darwin's theory removed from India's school textbooks Science educators urge restoration in open petition Educators say COVID-19 rationale to delete chapters not tenable [NEW DELHI] Science educators in India are urging the government to restore material on Darwinian evolution which has been removed from science textbooks on the grounds that the study load on schoolchildren needs to be lightened after the COVID-19 pandemic. "The theory of evolution by natural selection as propounded by Charles Darwin and developed and extended subsequently has had a major influence on modern biology and medicine, and indeed all of modern science. According to Raghunandan, Hindu mythology holds that the deity Vishnu descends to Earth as an "avatar” (form) whenever the cosmic order is disturbed.

Natural selection pressure exerted on "Silent" mutations during the evolution of SARS-CoV-2: Evidence from codon usage and RNA structure.

From the first emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) till now, multiple mutations that caused synonymous and nonsynonymous substitutions have accumulated. Among them, synonymous substitutions were regarded as "silent" mutations that received less attention than nonsynonymous substitutions that cause amino acid variations. However, the importance of synonymous substitutions can not be neglected. This research focuses on synonymous substitutions on SARS-CoV-2 and proves that synonymous substitutions were under purifying selection in its evolution. The evidence of purifying selection is provided by comparing the mutation number per site in coding and non-coding regions. We then study the two forces of purifying selection: synonymous codon usage and RNA secondary structure. Results show that the codon usage optimization leads to an adapted codon usage towards humans. Furthermore, our results show that the maintenance of RNA secondary structure causes the purifying of synonymous substitutions in the structural region. These results explain the selection pressure on synonymous substitutions during the evolution of SARS-CoV-2.

Attenuation and Degeneration of SARS-CoV-2 Despite Adaptive Evolution.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) has followed similar trends as other RNA viruses, such as human immunodeficiency virus type 1 and the influenza A virus. Rapid initial diversification was followed by strong competition and a rapid succession of dominant variants. Host-initiated RNA editing has been the primary mechanism for introducing mutations. A significant number of mutations detrimental to viral replication have been quickly purged. Fixed mutations are mostly diversifying mutations selected for host adaptation and immune evasion, with the latter accounting for the majority of the mutations. However, immune evasion often comes at the cost of functionality, and thus, optimal functionality is still far from being accomplished. Instead, selection for antibody-escaping variants and accumulation of near-neutral mutations have led to suboptimal codon usage and reduced replicative capacity, as demonstrated in non-respiratory cell lines. Beneficial adaptation of the virus includes reduced infectivity in lung tissues and increased tropism for the upper airway, resulting in shorter incubation periods, milder diseases, and more efficient transmission between people.

Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.

Genome Evolution and Early Introductions of the SARS-CoV-2 Omicron Variant in Mexico.

A new variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named Omicron (Pango lineage designation B.1.1.529), was first reported to the World Health Organization by South African health authorities on 24 November 2021. The Omicron variant possesses numerous mutations associated with increased transmissibility and immune escape properties. In November 2021, Mexican authorities reported Omicron's presence in the country. In this study, we infer the first introductory events of Omicron and the impact that human mobility has had on the spread of the virus. We also evaluated the adaptive evolutionary processes in Mexican SARS-CoV-2 genomes during the first month of the circulation of Omicron. We inferred 160 introduction events of Omicron in Mexico since its first detection in South Africa; subsequently, after the first introductions there was an evident increase in the prevalence of SARS-CoV-2 during January. This higher prevalence of the novel variant resulted in a peak of reported cases; on average 6 weeks after, a higher mobility trend was reported. During the peak of cases in the country from January to February 2022, the Omicron BA.1.1 sub-lineage dominated, followed by the BA.1 and BA.15 sub-lineages. Additionally, we identified the presence of diversifying natural selection in the genomes of Omicron and found six non-synonymous mutations in the receptor binding domain of the spike protein, all of them related to evasion of the immune response. In contrast, the other proteins in the genome are highly conserved; however, we identified homoplasic mutations in non-structural proteins, indicating a parallel evolution.

Comprehensive analysis of codon usage patterns of porcine deltacoronavirus and its host adaptability.

The porcine deltacoronavirus (PDCoV) is a newly discovered pig enteric coronavirus that can infect cells from various species. In Haiti, PDCoV infections in children with acute undifferentiated febrile fever were recently reported. Considering the great potential of inter-species transmission of PDCoV, we performed a comprehensive analysis of codon usage patterns and host adaptation profiles of 54 representative PDCoV strains with the spike (S) gene. Phylogenetic analysis of the PDCoV S gene indicates that the PDCoV strains can be divided into five genogroups. We found a certain codon usage bias existed in the S gene, in which the synonymous codons are often ended with U or A. Heat map analysis revealed that all the PDCoV strains shared a similar codon usage trend. The PDCoV S gene with a dN/dS ratio lower than 1 reveals a negative selection on the PDCoV S gene. Neutrality analysis showed that natural selection is the dominant force in shaping the codon usage bias of the PDCoV S gene. Unexpectedly, host adaptation analysis reveals a higher adaptation level of PDCoV to Homo sapiens and Gallus gallus than to Sus scrofa. Compared to the USA lineage, the PDCoV strains in the Early China lineage and Thailand lineage were less adapted to their hosts, which indicates that the evolutionary process plays an important role in the adaptation ability of PDCoV. These findings of this study add to our understanding of PDCoV's evolution, adaptability, and inter-species transmission.

Lineage-specific positive selection on ACE2 contributes to the genetic susceptibility of COVID-19.

The Angiotensin-Converting Enzyme-2 (ACE2) gene, located on Xp22.2, attracts a great deal of attention because the protein it encodes is believed to be the functional cellular receptor for the new coronavirus (SARS-CoV-2). However, recent studies are controversial, especially concerning the intrinsic link between ACE2 diversity and COVID-19 susceptibility. Here, we conduct a population genetic study on ACE2 in 6354 individuals representing 210 present-day populations and 5329 individuals of ancient or archaic groups. We dissected the genetic architecture of ACE2 and identified two major haplogroups (hg) in East Asians, i.e. ACE2-hg1 (43%) and ACE2-hg2 (53%), while other populations harbor more diverse ACE2-hgs. Accordingly, there was a significant loss of ACE2 common variations in East Asians in contrast to the X-chromosome-wide and genome-wide patterns. Notably, association analysis between ACE2-hgs and COVID-19 severity in 1229 Han Chinese individuals with various levels of COVID-19 severity showed a higher risk of ACE2-hg1 (odds ratio = 1.56, P < 0.01) and a lower risk of ACE2-hg2 (odds ratio = 0.65, P < 0.01). Interestingly, ACE2-hg1 is in strong linkage disequilibrium with rs1849863-C, which is an assumed risk factor of elevated plasma ACE2 level and is related to a higher risk of COVID-19 severity, hospitalization and infection. Strikingly, remarkable signatures of positive selection were detected, especially on ACE2-hg2, and were traced back to 100 000 years ago (but rose to a strong level during the Bronze Age, 5000∼3000 years ago, in East Asians). The selection pressures could have stemmed from multiple sources, but pre-COVID-19 viral epidemics and pandemics might have been potential driving forces, which consequently contributed to the genetic susceptibility to COVID-19 within and between populations.

RNA structure-altering mutations underlying positive selection on Spike protein reveal novel putative signatures to trace crossing host-species barriers in Betacoronavirus.

Similar to other RNA viruses, the emergence of Betacoronavirus relies on cross-species viral transmission, which requires careful health surveillance monitoring of protein-coding information as well as genome-wide analysis. Although the evolutionary jump from natural reservoirs to humans may be mainly traced-back by studying the effect that hotspot mutations have on viral proteins, it is largely unexplored if other impacts might emerge on the structured RNA genome of Betacoronavirus. In this survey, the protein-coding and viral genome architecture were simultaneously studied to uncover novel insights into cross-species horizontal transmission events. We analysed 1,252,952 viral genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 distributed across the world in bats, intermediate animals, and humans to build a new landscape of changes in the RNA viral genome. Phylogenetic analyses suggest that bat viruses are the most closely related to the time of most recent common ancestor of Betacoronavirus, and missense mutations in viral proteins, mainly in the S protein S1 subunit: SARS-CoV (G > T; A577S); MERS-CoV (C > T; S746R and C > T; N762A); and SARS-CoV-2 (A > G; D614G) appear to have driven viral diversification. We also found that codon sites under positive selection on S protein overlap with non-compensatory mutations that disrupt secondary RNA structures in the RNA genome complement. These findings provide pivotal factors that might be underlying the eventual jumping the species barrier from bats to intermediate hosts. Lastly, we discovered that nearly half of the Betacoronavirus genomes carry highly conserved RNA structures, and more than 90% of these RNA structures show negative selection signals, suggesting essential functions in the biology of Betacoronavirus that have not been investigated to date. Further research is needed on negatively selected RNA structures to scan for emerging functions like the potential of coding virus-derived small RNAs and to develop new candidate antiviral therapeutic strategies.

Natural selection plays a significant role in governing the codon usage bias in the novel SARS-CoV-2 variants of concern (VOC).

The ongoing prevailing COVID-19 pandemic caused by SARS-CoV-2 is becoming one of the major global health concerns worldwide. The SARS-CoV-2 genome encodes spike (S) glycoprotein that plays a very crucial role in viral entry into the host cell via binding of its receptor binding domain (RBD) to the host angiotensin converting enzyme 2 (ACE2) receptor. The continuously evolving SARS-CoV-2 genome results in more severe and transmissible variants characterized by the emergence of novel mutations called 'variants of concern' (VOC). The currently designated alpha, beta, gamma, delta and omicron VOC are the focus of this study due to their high transmissibility, increased virulence, and concerns for decreased effectiveness of the available vaccines. In VOC, the spike (S) gene and other non-structural protein mutations may affect the efficacies of the approved COVID-19 vaccines. To understand the diversity of SARS-CoV-2, several studies have been performed on a limited number of sequences. However, only a few studies have focused on codon usage bias (CUBs) pattern analysis of all the VOC strains. Therefore, to evaluate the evolutionary divergence of all VOC S-genes, we performed CUBs analysis on 300,354 sequences to understand the evolutionary relationship with its adaptation in different hosts, i.e., humans, bats, and pangolins. Base composition and RSCU analysis revealed the presence of 20 preferred AU-ended and 10 under-preferred GC-ended codons. In addition, CpG was found to be depleted, which may be attributable to the adaptive response by viruses to escape from the host defense process. Moreover, the ENC values revealed a higher bias in codon usage in the VOC S-gene. Further, the neutrality plot analysis demonstrated that S-genes analyzed in this study are under 83.93% influence of natural selection, suggesting its pivotal role in shaping the CUBs. The CUBs pattern of S-genes was found to be very similar among all the VOC strains. Interestingly, we observed that VOC strains followed a trend of antagonistic codon usage with respect to the human host. The identified CUBs divergence would help to understand the virus evolution and its host adaptation, thus help design novel vaccine strategies against the emerging VOC strains. To the best of our knowledge, this is the first report for identifying the evolution of CUBs pattern in all the currently identified VOC.

The Awesome Power of Human Genetics of Infectious Disease.

Since the identification of sickle cell trait as a heritable form of resistance to malaria, candidate gene studies, linkage analysis paired with sequencing, and genome-wide association (GWA) studies have revealed many examples of genetic resistance and susceptibility to infectious diseases. GWA studies enabled the identification of many common variants associated with small shifts in susceptibility to infectious diseases. This is exemplified by multiple loci associated with leprosy, malaria, HIV, tuberculosis, and coronavirus disease 2019 (COVID-19), which illuminate genetic architecture and implicate pathways underlying pathophysiology. Despite these successes, most of the heritability of infectious diseases remains to be explained. As the field advances, current limitations may be overcome by applying methodological innovations such as cellular GWA studies and phenome-wide association (PheWA) studies as well as by improving methodological rigor with more precise case definitions, deeper phenotyping, increased cohort diversity, and functional validation of candidate loci in the laboratory or human challenge studies.

Containing the spread of COVID-19 virus facing to its high mutation rate: approach to intervention using a nonspecific way of blocking its entry into the cells.

Viruses have multiple mutation rates that are higher than any other member of the kingdom of life. This gives them the ability to evolve, even within the course of a single infection, and to evade multiple host defenses, thereby impacting pathogenesis. Additionally, there are also interplays between mutation and recombination and the high multiplicity of infection (MOI) that enhance viral adaptability and increase levels of recombination leading to complex and conflicting effects on genome selection, and the net results is difficult to predict. Recently, the outbreak of COVID-19 virus represents a pandemic threat that has been declared a public health emergency of international concern. Up to present, however, due to the high mutation rate of COVID-19 virus, there are no effective procedures to contain the spread of this virus across the globe. For such a purpose, there is then an urgent need to explore new approaches. As an opinion, the present approach emphasizes on (a) the use of a nonspecific way of blocking the entry of COVID-19 virus as well as its variants into the cells via a therapeutic biocompatible compound (ideally, "in a pill") targeting its spike (S) glycoprotein; and (b) the construction of expression vectors via the glycosyl-phosphatidylinositol, GPI, anchor for studying intermolecular interactions between the spike S of COVID-19 virus as well as its variants and the angiotensin-converting enzyme 2 (ACE2) of its host receptor for checking the efficacy of any therapeutic biocompatible compound of the nonspecific way of blocking. Such antiviral drug would be safer than the ACE1 and ACE2 inhibitors/angiotensin receptor blockers, and recombinant human ACE2 as well as nucleoside analogs or protease inhibitors used for fighting the spread of the virus inside the cells, and it would also be used as a universal one for any eventual future pandemic related to viruses, especially the RNA viruses with high mutation rates.

An Evolutionary Insight Into the Heterogeneous Severity Pattern of the SARS-CoV-2 Infection.

The ongoing pandemic of COVID-19 has elaborated an idiosyncratic pattern of SARS-CoV-2-induced symptoms in the human host. Some populations have succumbed to the SARS-CoV-2 infection in large numbers during this pandemic, whereas others have shown a resilient side by manifesting only milder or no symptoms at all. This observation has relayed the onus of the heterogeneous pattern of SARS-CoV-2-induced critical illness among different populations to the host genetic factors. Here, the evolutionary route was explored and three genetic loci, i.e., rs10735079, rs2109069, and rs2236757, associated with COVID-19 were analyzed. Among the three, the risk allele A at genetic locus rs2236757 residing in the IFNAR2 gene was observed to have undergone recent positive selection in the African population.

Covid-19: Is it a biological weapon?

According to official sources, the COVID-19 epidemic caused by the new type of coronavirus, which started in the late December 2019 in the city of Wuhan, China, as atypical pneumonia cases of unknown origin, then spread to Iran, then to all of Europe and the United States through Italy, and finally to the whole world. It has become widespread in our country after the March 2019 and has become the main agenda of our social life with the quarantine and isolation measures that have been gradually expanded. Scientists have put forward many thoughts and findings about the origin and evolution of the virus since the epidemic first broke out, and on the other hand, they sought an answer to the question of whether it is a biological weapon produced in the laboratory. Hypotheses about whether the virus was created by nature as a result of natural selection or whether it is a human-made virus still remain on the agenda. Although it is prohibited by international signed conventions, the possibility of producing the coronavirus for the purpose of using as a biological weapon or revealing the origin of the virus will also include the answers to what our future will be like in this epidemic and thereafter. In this presentation, the concept of biological warfare, the characteristics of biological weapons, and in this context, where the COVID-19 epidemic is in these concepts, and the evaluation of the virus in terms of biological weapons will be evaluated.

Codon Usage and Phenotypic Divergences of SARS-CoV-2 Genes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2.

POSSIBLE MUTATION PATHWAYS IN SARS-CoV-2

Mutations are the best way to generate genetic variation, as they provide the raw material in which evolutionary forces, like natural selection, can act. However, mutations are not always able to change the apparent behaviour of an organism, instead, they are capable of providing normal and abnormal biological functions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a new and controversial biological scenario. Despite the hundreds of studies performed, to date, there is no specific treatment available. Several genomic and non-genomic mutations have been also reported, and due to its high genome size and mutation capacity, it can acclimatize to variable environments and has become the leading cause of high infection and mortality rates. This review outlines the possible pathways behind SARS-CoV-2 mutations.