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Schuster, S. C.

Publications and source records attributed to Schuster, S. C..

10 recordsLinked to original sources

Maize genetic diversity is largely unstructured by human ethnolinguistic diversity in its center of origin

Population structure and environmental features often capture major axes of genetic variation in many species. Yet the impacts of human activity often remain unquantified. For domesticated species that rely on human activity for survival and dispersal, human movements and cultural differences may play key roles patterning genetic diversity. Maize is a staple crop of enormous cultural importance to indigenous peoples of the Americas, but cannot survive or disperse without farmers. Using publicly available genotyping and passport data from almost 2,000 traditional maize varieties, more than 500 whole genome sequences of humans from Mexico, and indigenous linguistic maps, we quantify anthropogenic effects on maize genetic diversity in the Americas. Maize shows very little overall structure, highlighting the effectiveness of indigenous farmers in moving and mixing maize populations. While principal components of maize diversity show meaningful correlations to human genetic diversity, our linear modeling suggests little additional impact of human population structure beyond shared geography. Though differences in maize diversity are often patterned by language locally, we find only weak genome-wide effects at larger spatial scales. Despite the relatively weak global signal of anthropogenic effects, linguistic GWAS, outlier FST analyses, and selection scans identified loci associated with specific languages. Leveraging landscape-level sequencing data, we highlight how anthropogenic factors have shaped patterns of maize genetic diversity across Mesoamerica.

evolutionary biology↗

The Interplay Between Nutrition and the Midgut Microbiome of the Mosquito Aedes aegypti Reveals Putative Symbionts.

Blood meals are crucial for the reproductive cycle of Aedes aegypti and represent the means by which arboviruses are transmitted to its hematophagy hosts. It also has been postulated that feeding on blood may modulate the mosquito microbiome, but the compositional shifts in microbial diversity and function remain elusive. In this paper, we analyzed the modulation of the midgut microbiome in 60 females of Aedes aegypti throughout the digestive period, 12, 24, and 48 hours after blood or sugar meals using whole-genome shotgun sequencing. Microbial transstadial transmission between larvae and adults was also assessed. This approach provided a high coverage of the midgut metagenome, allowing microbial taxonomic assignments at the species level and gene-based functional profiling. Females at later hours post-feeding and larvae display low microbiome diversities and little evidence of transstadial transmission. However, a striking proliferation of Enterobacterales was observed during early hours of digestion in blood-fed mosquitoes. The compositional shift was concomitant with a predicted functional change in genes associated with carbohydrate and protein metabolism. The observed shifts in blood-fed females midguts are restored to a sugar-fed-like microbial profile after 48h, when blood digestion is completed. Conversely, as in all blood-fed females, a high abundance of the opportunistic human pathogen Elizabethkingia anophelis (Flavobacteriales) takes place in this post-digestion stage. This bacterial species has also been described as a symbiont of mosquitoes of the genus Anopheles (Culicidae). This work is the first report of the adaptation of the midgut microbiome of A. aegypti to a digestive role after a blood meal, at the expense of the proliferation of potential symbionts. Significance statementThe findings in this paper can contribute to a better understanding of the dynamics of the mosquito microbiome during digestion and its potential implications for host physiology and metabolism, also informing the future development of sustainable methods for insect-borne diseases control based on microbial components that might influence vectorial capacity and pathogen transmission by A. aegypti.

microbiology↗

Insights into bear evolution from a Pleistocene polar bear genome

The polar bear (Ursus maritimus) has become a symbol of the threat to biodiversity from climate change. Understanding polar bear evolutionary history may provide insights into apex carnivore responses and prospects during periods of extreme environmental perturbations. In recent years, genomic studies have examined bear speciation and population history, including evidence for ancient admixture between polar bears and brown bears (Ursus arctos). Here, we extend our earlier studies of a 130,000-115,000-year-old polar bear from the Svalbard Archipelago using a 10X coverage genome sequence and ten new genomes of polar and brown bears from contemporary zones of overlap in northern Alaska. We demonstrate a dramatic decline in effective population size for this ancient polar bears lineage, followed by a modest increase just before its demise. A slightly higher genetic diversity in the ancient polar bear suggests a severe genetic erosion over a prolonged bottleneck in modern polar bears. Statistical fitting of data to alternative admixture graph scenarios favors at least one ancient introgression event from brown bears into the ancestor of polar bears, possibly dating back over 150,000 years. Gene flow was likely bidirectional, but allelic transfer from brown into polar bear is the strongest detected signal, which contrasts with other published works. These findings may have implications for our understanding of climate change impacts: polar bears, a specialist Arctic lineage, may not only have undergone severe genetic bottlenecks, but also been the recipient of generalist, boreal genetic variants from brown bear during critical phases of Northern Hemisphere glacial oscillations. SignificanceInterspecific hybridization is a widespread phenomenon, but measuring its extent, directionality, and adaptive importance remains challenging. Ancient genomes, however, can help illuminate the history of modern organisms. Here, we present a genome retrieved from a 130,000-115,000-year-old polar bear and perform genome analyses of modern polar and brown bears throughout their geographic range. We find that the principal direction of ancient allele sharing was from brown bear into polar bear, although gene flow between them has likely been bidirectional. This inverts the current paradigm of unidirectional gene flow from polar into brown bear, and it suggests that polar bears were recipients of external genetic variation prior to their extensive population decline.

evolutionary biology↗

Recovery of high quality metagenome-assembled genomes from full-scale activated sludge microbial communities in a tropical climate using longitudinal metagenome sampling

Analysis of metagenome data based on the recovery of draft genomes (so called metagenome-assembled genomes, or MAG) have assumed an increasingly central role in microbiome research in recent years. Microbial communities underpinning the operation of wastewater treatment plants are particularly challenging targets for MAG analysis due to their high ecological complexity, and remain important, albeit understudied, microbial communities that play a key role in mediating interactions between human and natural ecosystems. In this paper, we consider strategies for recovery of MAG sequence from time series metagenome surveys of full-scale activated sludge microbial communities. We generate MAG catalogues from this set of data using several different strategies, including the use of multiple individual sample assemblies, two variations on multi-sample co-assembly and a recently published MAG recovery workflow using deep learning. We obtain a total of just under 9,100 draft genomes, which collapse to around 3,100 non-redundant genomic clusters. We examine the strengths and weaknesses of these approaches in relation to MAG yield and quality, showing the co-assembly offers clear advantages over single-sample assembly. Around 1000 MAGs were candidates for being considered high quality, based on single-copy marker gene occurrence statistics, however only 58 MAG formally meet the MIMAG criteria for being high quality draft genomes. These findings carry broader implications for performing genome-resolved metagenomics on highly complex communities, the design and implementation of genome recoverability strategies, MAG decontamination and the search for better binning methodology.

genomics↗

Evolutionary and phylogenetic insights from a nuclear genome sequence of the extinct, giant subfossil koala lemur Megaladapis edwardsi

No endemic Madagascar animal with body mass >10 kg survived a relatively recent wave of extinction on the island. From morphological and isotopic analyses of skeletal subfossil remains we can reconstruct some of the biology and behavioral ecology of giant lemurs (primates; up to ~160 kg), elephant birds (up to ~860 kg), and other extraordinary Malagasy megafauna that survived well into the past millennium. Yet much about the evolutionary biology of these now extinct species remains unknown, along with persistent phylogenetic uncertainty in some cases. Thankfully, despite the challenges of DNA preservation in tropical and sub-tropical environments, technical advances have enabled the recovery of ancient DNA from some Malagasy subfossil specimens. Here we present a nuclear genome sequence (~2X coverage) for one of the largest extinct lemurs, the koala lemur Megaladapis edwardsi (~85kg). To support the testing of key phylogenetic and evolutionary hypotheses we also generated new high-coverage complete nuclear genomes for two extant lemur species, Eulemur rufifrons and Lepilemur mustelinus, and we aligned these sequences with previously published genomes for three other extant lemur species and 47 non-lemur vertebrates. Our phylogenetic results confirm that Megaladapis is most closely related to the extant Lemuridae (typified in our analysis by E. rufifrons) to the exclusion of L. mustelinus, which contradicts morphology-based phylogenies. Our evolutionary analyses identified significant convergent evolution between M. edwardsi and extant folivorous primates (colobine monkeys) and ungulate herbivores (horses) in genes encoding protein products that function in the biodegradation of plant toxins and nutrient absorption. These results suggest that koala lemurs were highly adapted to a leaf-based diet, which may also explain their convergent craniodental morphology with the small-bodied folivore Lepilemur.

genomics↗

Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. It is a highly contagious positive strand RNA virus and its clinical presentation includes severe to critical respiratory disease that appears to be fatal in [~]3-5% of the cases. The viral spike (S) coat protein engages the human angiotensin-converting enzyme2 (ACE2) cell surface protein to invade the host cell. The SARS-CoV-2 S-protein has acquired mutations that increase its affinity to human ACE2 by [~]10-15-fold compared to SARS-CoV S-protein, making it highly infectious. In this study, we assessed if ACE2 polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 S-protein interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 protein-altering variants, some of which mapped to the S-protein-interacting ACE2 surface. Using recently reported structural data and a recent S-protein-interacting synthetic mutant map of ACE2, we have identified natural ACE2 variants that are predicted to alter the virus-host interaction and thereby potentially alter host susceptibility. In particular, human ACE2 variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R are predicted to increase susceptibility. The T92I variant, part of a consensus NxS/T N-glycosylation motif, confirmed the role of N90 glycosylation in immunity from non-human CoVs. Other ACE2 variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y are putative protective variants predicted to show decreased binding to SARS-CoV-2 S-protein. Overall, ACE2 variants are rare, consistent with the lack of selection pressure given the recent history of SARS-CoV epidemics, however, are likely to play an important role in altering susceptibility to CoVs.

genetics↗

The Chinese chestnut genome: a reference for species restoration

Forest tree species are increasingly subject to severe mortalities from exotic pests, diseases, and invasive organisms, accelerated by climate change. Forest health issues are threatening multiple species and ecosystem sustainability globally. While sources of resistance may be available in related species, or among surviving trees, introgression of resistance genes into threatened tree species in reasonable time frames requires genome-wide breeding tools. Asian species of chestnut (Castanea spp.) are being employed as donors of disease resistance genes to restore native chestnut species in North America and Europe. To aid in the restoration of threatened chestnut species, we present the assembly of a reference genome with chromosome-scale sequences for Chinese chestnut (C. mollissima), the disease-resistance donor for American chestnut restoration. We also demonstrate the value of the genome as a platform for research and species restoration, including new insights into the evolution of blight resistance in Asian chestnut species, the locations in the genome of ecologically important signatures of selection differentiating American chestnut from Chinese chestnut, the identification of candidate genes for disease resistance, and preliminary comparisons of genome organization with related species.

genomics↗

Whole-genome reference panel of 1,781 Northeast Asians improves imputation accuracy of rare and low-frequency variants

Genotype imputation using the reference panel is a cost-effective strategy to fill millions of missing genotypes for the purpose of various genetic analyses. Here, we present the Northeast Asian Reference Database (NARD), including whole-genome sequencing data of 1,781 individuals from Korea, Mongolia, Japan, China, and Hong Kong. NARD provides the genetic diversities of Korean (n=850) and Mongolian (n=386) ancestries that were not present in the 1000 Genomes Project Phase 3 (1KGP3). We combined and re-phased the genotypes from NARD and 1KGP3 to construct a union set of haplotypes. This approach established a robust imputation reference panel for the Northeast Asian populations, which yields the greatest imputation accuracy of rare and low-frequency variants compared with the existing panels. Also, we illustrate that NARD can potentially improve disease variant discovery by reducing pathogenic candidates. Overall, this study provides a decent reference panel for the genetic studies in Northeast Asia.

genomics↗

The Acquisition of Resistance to Carbapenem and Macrolide-mediated Quorum Sensing Inhibition by Pseudomonas aeruginosa via a Novel Integrative and Conjugative Element ICETn43716385

Pseudomonas aeruginosa can cause persistant and life-threatening infections in immunocompromised patients. Carbapenems are the first-line agents to treat P. aeruginosa infections; therefore, the emergence of carbapenem-resistant P. aeruginosa strains has greatly challenged effective antibiotic therapy. In this study, we characterised the full-length genomes of two carbapenem resistant P. aeruginosa clinical isolates that produce the carbapebemase New Delhi metallo-{beta}-lactamase-1 (NDM-1). We found that the blaNDM-1 gene is encoded by a novel intergrative and conjugative element (ICE) ICETn43716385, which also carries the macrolide resistance gene msr(E) and the florfenicol resistance gene floR. The msr(E) gene has rarely been described in P. aeruginosa genomes. To investigate the functional roles of msr(E) in P. aeruginosa, we exogeneously expressed this gene in P. aeruginosa laboratory strains and found that the acquisition of msr(E) could abolish the azithromycin-mediated quorum sensing inhibition in vitro and the anti-Pseudomonas effect of azithromycin in vivo. In addition, the expression of msr(E) almost completely restored the azithromycin-affected P. aeruginosa transcriptome, as shown by our RNA sequencing analysis. We present the first evidence of blaNDM-1 to be carried by intergrative and conjugative elements, and the first evidence of co-transfer of carbapenem resistance and the resistance to macrolide-mediated quorum sensing inhibition into P. aeruginosa genomes.\n\nImportanceCarbapenem resistant P. aeruginosa has recently been listed as the top three most dangerous superbugs by World Health Organisation. The transmission of blaNDM-1 gene into P. aeruginosa can cause extreme resistance to carbapenems and fourth generation cephalosporins, which greatly compromises the effectiveness of these antibiotics against Pseudomonas infections. However, the lack of complete genome sequence of NDM-1-producing P. aeruginosa has limited our understanding of the transmisibility of blaNDM-1 in this organism. Here we showed the co-transfer of blaNDM-1 and msr(E) into P. aeruginosa genome by a novel integrative and conjugative element (ICE). The acquisition of these two genes confers P. aeruginosa with resistance to carbapenem and macrolide-mediated quorum sensing inhibition, both of which are important treatment stretagies for P. aeruginosa infections. Our findings highlight the potential of ICEs in transmitting carbapenem resistance, and that the anti-virulence treatment of P. aeruginosa infections by macrolides can be challenged by horizontal gene transfer.

genomics↗

Cyclic-di-GMP is required for corneal infection by Pseudomonas aeruginosa and modulates host immunity

Biofilms are extremely tolerant toward antimicrobial treatment and host immune clearance due to their distinct physiology and protection by extracellular polymeric substances. Bis-(3{acute}-5{acute})-cyclic dimeric guanosine monophosphate (c-di-GMP) is an essential messenger that regulates biofilm formation by a wide range of bacteria. However, there is a lack of physiological characterization of biofilms in vivo as well as the roles of c-di-GMP signaling in mediating host-biofilm interactions. Here, we employed dual RNA-Seq to characterize the host and pathogen transcriptomes during Pseudomonas aeruginosa infection using a mouse keratitis model. In vivo P. aeruginosa biofilms maintained a distinct physiology compared with in vitro P. aeruginosa biofilms, with enhanced virulence and iron uptake capacity. C-di-GMP synthesis was enhanced in P. aeruginosa cells in vivo, potentially due to down-regulation of the expression of several phosphodiesterases (e.g., DipA, NbdA). Increased intracellular c-di-GMP levels were required for long-term ocular colonization of P. aeruginosa and impaired host innate immunity.

microbiology↗