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Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.

The timing of the dispersal of anatomically modern humans (AMH) out of Africa is a fundamental question in human evolutionary studies. Existing data suggest a rapid coastal exodus via the Indian Ocean rim around 60,000 years ago. We present evidence from Jebel Faya, United Arab Emirates, demonstrating human presence in eastern Arabia during the last interglacial. The tool kit found at Jebel Faya has affinities to the late Middle Stone Age in northeast Africa, indicating that technological innovation was not necessary to facilitate migration into Arabia. Instead, we propose that low eustatic sea level and increased rainfall during the transition between marine isotope stages 6 and 5 allowed humans to populate Arabia. This evidence implies that AMH may have been present in South Asia before the Toba eruption (1).

The four human coronaviruses (HCoVs) are globally endemic respiratory pathogens. The Middle East respiratory syndrome (MERS) coronavirus (CoV) is an emerging CoV with a known zoonotic source in dromedary camels. Little is known about the origins of endemic HCoVs. Studying these viruses’ evolutionary history could provide important insight into CoV emergence. In tests of MERS-CoV–infected dromedaries, we found viruses related to an HCoV, known as HCoV-229E, in 5.6% of 1,033 animals. Human- and dromedary-derived viruses are each monophyletic, suggesting ecological isolation. One gene of dromedary viruses exists in two versions in camels, full length and deleted, whereas only the deleted version exists in humans. The deletion increased in size over a succession starting from camelid viruses via old human viruses to contemporary human viruses. Live isolates of dromedary 229E viruses were obtained and studied to assess human infection risks. The viruses used the human entry receptor aminopeptidase N and replicated in human hepatoma cells, suggesting a principal ability to cause human infections. However, inefficient replication in several mucosa-derived cell lines and airway epithelial cultures suggested lack of adaptation to the human host. Dromedary viruses were as sensitive to the human type I interferon response as HCoV-229E. Antibodies in human sera neutralized dromedary-derived viruses, suggesting population immunity against dromedary viruses. Although no current epidemic risk seems to emanate from these viruses, evolutionary inference suggests that the endemic human virus HCoV-229E may constitute a descendant of camelid-associated viruses. HCoV-229E evolution provides a scenario for MERS-CoV emergence.

The advent of embryophytes (land plants) is among the most important evolutionary breakthroughs in Earth history. It irreversibly changed climates and biogeochemical processes on a global scale; it allowed all eukaryotic terrestrial life to evolve and to invade nearly all continental environments. Before this work, the earliest unequivocal embryophyte traces were late Darriwilian (late Middle Ordovician; c. 463-461 million yr ago (Ma)) cryptospores from Saudi Arabia and from the Czech Republic (western Gondwana). Here, we processed Dapingian (early Middle Ordovician, c. 473-471 Ma) palynological samples from Argentina (eastern Gondwana). We discovered a diverse cryptospore assemblage, including naked and envelope-enclosed monads and tetrads, representing five genera. Our discovery reinforces the earlier suggestion that embryophytes first evolved in Gondwana. It indicates that the terrestrialization of plants might have begun in the eastern part of Gondwana. The diversity of the Dapingian assemblage implies an earlier, Early Ordovician or even Cambrian, origin of embryophytes. Dapingian to Aeronian (Early Silurian) cryptospore assemblages are similar, suggesting that the rate of embryophyte evolution was extremely slow during the first c. 35-45 million yr of their diversification. The Argentinean cryptospores predate other cryptospore occurrences by c. 8-12 million yr, and are currently the earliest evidence of plants on land.

Several significant milestones in human evolution date to the period between 70,000 and 12,000 years ago, including the replacement of archaic humans, the global dispersal of Homo sapiens and the introduction of Upper Palaeolithic traditions. The Arabian Peninsula provides only sparse records illuminating this period. We introduce here the Buhais Rockshelter archaeological sequence and paleoenvironmental records from the Faya Palaeolandscape in the Emirate of Sharjah (UAE). Buhais Rockshelter provides stratified stone artifact assemblages reflecting habitation phases around 125,000, 59,000, 35,000 and 16,000 years ago. Palaeoenvironmental fieldwork further shows that settlement at Buhais Rockshelter is contemporaneous with increased water availability in the landscape at these times. Our results contradict the prevailing view of human absence in Arabia at the end of the Pleistocene and call for reassessing the inhabitability of southern Arabia during the last glacial period. Results from Buhais Rockshelter extend known records from Jebel Faya and demonstrate repeated occupation of the region between 210,000 and 16,000 years ago. Together, this contributes data for a critical timeframe in human evolution providing an empirical foundation for testing anthropological models about human adaptation to and dispersal through the desert landscapes of southern Arabia. The authors present an archaeological sequence and paleoenvironmental proxies from the Buhais Rockshelter (UAE) dating to between 60-16,000 years ago. They demonstrate that human occupation of this arid landscape corresponded with increased water availability, expanding a limited archaeological record in this region.

The study underpins barcode characterization of insect species collected from Saudi Arabia and explored functional constraints during evolution at the DNA and protein levels to expect the possible mechanisms of protein evolution in insects. Codon structure designated AT-biased insect barcode of the cytochrome C oxidase I (COI). In addition, the predicted 3D structure of COI protein indicated tyrosine in close proximity with the heme ligand, depicted substitution to phenylalanine in two Hymenopteran species. This change resulted in the loss of chemical bonding with the heme ligand. The estimated nucleotide substitution matrices in insect COI barcode generally showed a higher probability of transversion compared with the transition. Computations of codon-by-codon nonsynonymous substitutions in Hymenopteran and Hemipteran species indicated that almost half of the codons are under positive evolution. Nevertheless, codons of COI barcode of Coleoptera, Lepidoptera and Diptera are mostly under purifying selection. The results reinforce that codons in helices 2, 5 and 6 and those in loops 2-3 and 5-6 are mostly conserved and approach strong purifying selection. The overall results argue the possible evolutionary position of Hymenopteran species among those of other insects.

Background Osteogenesis imperfecta (OI) is an hereditary bone disease in which increased bone fragility leads to frequent fractures and other complications, usually in an autosomal dominant fashion. An expanding list of genes that encode proteins related to collagen metabolism are now recognised as important causes of autosomal recessive (AR) OI. Our aim was to study the contribution of known genes to AR OI in order to identify novel loci in mutation-negative cases. Methods We enrolled multiplex consanguineous families and simplex cases (also consanguineous) in which mutations in COL1A1 and COL1A2 had been excluded. We used autozygome guided mutation analysis of AR OI (AR OI) genes followed by exome sequencing when such analysis failed to identify the causative mutation. Results Two simplex and 11 multiplex families were enrolled, encompassing 27 cases. In three multiplex families, autozygosity and linkage analysis revealed a novel recessive OI locus on chromosome 9q31.1-31.3, and a novel truncating deletion of exon 4 of TMEM38B was identified within that interval. In addition, gonadal or gonadal/somatic mosaic mutations in COL1A1 or COL1A2 and homozygous mutations in recently described AR OI genes were identified in all remaining families. Conclusions TMEM38B is a novel candidate gene for AR OI. Future studies are needed to explore fully the contribution of this gene to AR OI in other populations.

The earliest metazoans Chemical fossils discovered in sedimentary rocks in Oman provide the earliest evidence for animal life so far discovered. The fossil steroids — 24-isopropylcholestanes characteristic of sponges of the Demospongiae class — date back 635 million years or more to around the time of the Marinoan glaciation, the last of the immense ice ages at the end of the Neoproterozoic. This suggests that the shallow waters in some late Cryogenian ocean basins contained dissolved oxygen in concentrations sufficient to support simple multicellular organisms at least 100 million years before the rapid diversification of bilaterians during the Cambrian explosion. This paper reports chemical fossils characteristic of sponges that date back at least 635 million years ago, constituting the earliest evidence yet found for animal life. The sponges lived during the Marinoan glaciation, the last of the immense ice ages at the end of the Neoproterozoic. No evidence has been found for animal life during the earlier Sturtian glaciation. The Neoproterozoic era (1,000–542 Myr ago) was an era of climatic extremes and biological evolutionary developments culminating in the emergence of animals (Metazoa) and new ecosystems 1 . Here we show that abundant sedimentary 24-isopropylcholestanes, the hydrocarbon remains of C 30 sterols produced by marine demosponges, record the presence of Metazoa in the geological record before the end of the Marinoan glaciation (∼635 Myr ago). These sterane biomarkers are abundant in all formations of the Huqf Supergroup, South Oman Salt Basin, and, based on a new high-precision geochronology 2 , constitute a continuous 100-Myr-long chemical fossil record of demosponges through the terminal Neoproterozoic and into the Early Cambrian epoch. The demosponge steranes occur in strata that underlie the Marinoan cap carbonate (>635 Myr ago). They currently represent the oldest evidence for animals in the fossil record, and are evidence for animals pre-dating the termination of the Marinoan glaciation. This suggests that shallow shelf waters in some late Cryogenian ocean basins (>635 Myr ago) contained dissolved oxygen in concentrations sufficient to support basal metazoan life at least 100 Myr before the rapid diversification of bilaterians during the Cambrian explosion. Biomarker analysis has yet to reveal any convincing evidence for ancient sponges pre-dating the first globally extensive Neoproterozoic glacial episode (the Sturtian, ∼713 Myr ago in Oman 2 ).

Introduction Human metapneumovirus (HMPV) is a major viral cause of acute respiratory tract infections, especially in young children and older adults. However, data on its molecular epidemiology in the Middle East remain scarce. As the COVID-19 pandemic may have altered the circulation and molecular epidemiology of respiratory viruses, this study represents one of the first efforts to assess the genetic diversity and circulation patterns of HMPV in Saudi Arabia during the COVID-19 era. Methods A total of 216 nasopharyngeal aspirates were collected from hospitalized children with suspected respiratory infections in Riyadh during the COVID-19 pandemic. Samples were screened for HMPV by RT-PCR, and the full-length G gene of positive isolates was amplified, sequenced, and analyzed for phylogeny, mutations, and glycosylation profiles. Results HMPV was detected in 10 (4.63%) of screened samples, with the highest prevalence among children aged 2–5 months and a predominance in males. Co-infections with other respiratory viruses were observed in 5 (50%) positive cases. Phylogenetic analysis identified five distinct genotypes (A2.1, A2.2, A2.2.2, B1, B2). Notably, genotype A2.2.2 was identified for the first time in Saudi Arabia and the Middle East region. Comparative sequence analysis revealed 43.75% nucleotide mutations and 25.83% amino acid substitutions, many of which were genotype-specific, along with distinct glycosylation patterns unique to the study isolates. Conclusion This study provides the first molecular characterization of HMPV in Saudi Arabia during the COVID-19 pandemic. The results demonstrate notable genetic diversity, including the circulation of five genotypes and the first detection of the A2.2.2 genotype in the country. These findings highlight the importance of continuous genomic surveillance to monitor viral evolution and guide regional public-health strategies. Clinical trial number Not applicable.