SARS-CoV-2 variants of concern elicit divergent early immune responses in hACE2 transgenic mice.

Knowledge about early immunity to SARS-CoV-2 variants of concern mainly comes from the analysis of human blood. Such data provide limited information about host responses at the site of infection and largely miss the initial events. To gain insights into compartmentalization and the early dynamics of host responses to different SARS-CoV-2 variants, we utilized human angiotensin converting enzyme 2 (hACE2) transgenic mice and tracked immune changes during the first days after infection by RNAseq, multiplex assays, and flow cytometry. Viral challenge infection led to divergent viral loads in the lungs, distinct inflammatory patterns, and innate immune cell accumulation in response to ancestral SARS-CoV-2, Beta (B.1.351) and Delta (B.1.617.2) variant of concern (VOC). Compared to other SARS-CoV-2 variants, infection with Beta (B.1.351) VOC spread promptly to the lungs, leading to increased inflammatory responses. SARS-CoV-2-specific antibodies and T cells developed within the first 7 days postinfection and were required to reduce viral spread and replication. Our studies show that VOCs differentially trigger transcriptional profiles and inflammation. This information contributes to the basic understanding of immune responses immediately postexposure to SARS-CoV-2 and is relevant for developing pan-VOC interventions including prophylactic vaccines.

Molecular ecology of the sleeper shark subgenus Somniosus (Somniosus) reveals genetic homogeneity within species and lack of support for S. antarcticus.

Inferences made from molecular data support regional stock assessment goals by providing insights into the genetic population dynamics of enigmatic species. Population genomics metrics, such as genetic diversity and population connectivity, serve as useful proxies for species health and stability. Sleeper sharks (genus Somniosus) are ecologically important deep-sea predators, estimated to reach ages of 250 to 300 yr and taking decades to reach sexual maturity. The subgenus Somniosus (Somniosus) is comprised of 3 species: S. pacificus, S. microcephalus, and S. antarcticus. Given the life history strategy of somniosids, they are vulnerable to overfishing and population declines. Further, data to assess the stocks of these species are limited. To address this deficiency, we used the reduced representation library method Restriction-site Associated DNA sequencing (RADseq) to conduct phylogenomic and population genomics analyses, providing novel information for use in stock assessments. Our results strongly support the species status of S. microcephalus (N = 79), but recover S. antarcticus (N = 2) intermixed within the S. pacificus (N = 170) clade. Population genomics analyses reveal genetic homogeneity within S. pacificus and S. microcephalus, and estimates of effective population size were in the hundreds for both species. Kinship analysis identified 2 first-degree relative pairs within our dataset (1 within each species). Our results contribute new information for stock assessments of these uniquely long-lived species by providing the strongest molecular evidence to date for the synonymization of S. antarcticus and S. pacificus, as well as estimating population genomic metrics for each supported species within the Somniosus (Somniosus) subgenus.

Genomic Analyses Implicate the Amazon-Orinoco Plume as the Driver of Cryptic Speciation in a Swimming Crab.

The Amazon-Orinoco plume (AOP) is the world's largest freshwater and sediment discharge into the ocean. Previous studies limited to mtDNA suggest that the swimming crab Callinectes ornatus Ordway, 1863 exists as two distinct genetic clusters separated by the AOP. However, questions concerning migration, diversification time, and species delimitation are unresolved. Densely sampling markers across the genome (SNPs) could elucidate the evolutionary processes within this species. Here, we combined mtDNA data and ddRAD-seq to explore the diversification patterns and processes within the swimming crab C. ornatus. We show great genetic differentiation between groups on the north and south sides of the plume but also signs of hybridization. Demographic modeling indicates the divergence between groups starting around 8 Mya following the AOP's formation. After a period of isolation, we detect two incidences of secondary contact with stronger migration in concordance with the North Brazil Current flow. Our results suggest speciation with gene flow explained by the interplay among the AOP, oceanographic currents, and long larval dispersal. This work represents the first investigation employing ddRAD-seq in a marine invertebrate species with distribution encompassing the north and south Atlantic and sheds light on the role of the AOP in the diversification of a marine species.

Population genomic analyses of schistosome parasites highlight critical challenges facing endgame elimination efforts.

Schistosomiasis persists in Asian regions despite aggressive elimination measures. To identify factors enabling continued parasite transmission, we performed reduced representation genome sequencing on Schistosoma japonicum miracidia collected across multiple years from transmission hotspots in Sichuan, China. We discovered strong geographic structure, suggesting that local, rather than imported, reservoirs are key sources of persistent infections in the region. At the village level, parasites collected after referral for praziquantel treatment are closely related to local pre-treatment populations. Schistosomes within villages are also highly related, suggesting that only a few parasites from a limited number of hosts drive re-infection. The close familial relationships among miracidia from different human hosts also implicate short transmission routes among humans. At the individual host level, genetic evidence indicates that multiple humans retained infections following referral for treatment. Our findings suggest that end-game schistosomiasis control measures should focus on completely extirpating local parasite reservoirs and confirming successful treatment of infected human hosts.

Patterns of relatedness and genetic diversity inferred from whole genome sequencing of archival blood fluke miracidia (Schistosoma japonicum).

Genomic approaches hold great promise for resolving unanswered questions about transmission patterns and responses to control efforts for schistosomiasis and other neglected tropical diseases. However, the cost of generating genomic data and the challenges associated with obtaining sufficient DNA from individual schistosome larvae (miracidia) from mammalian hosts have limited the application of genomic data for studying schistosomes and other complex macroparasites. Here, we demonstrate the feasibility of utilizing whole genome amplification and sequencing (WGS) to analyze individual archival miracidia. As an example, we sequenced whole genomes of 22 miracidia from 11 human hosts representing two villages in rural Sichuan, China, and used these data to evaluate patterns of relatedness and genetic diversity. We also down-sampled our dataset to test how lower coverage sequencing could increase the cost effectiveness of WGS while maintaining power to accurately infer relatedness. Collectively, our results illustrate that population-level WGS datasets are attainable for individual miracidia and represent a powerful tool for ultimately providing insight into overall genetic diversity, parasite relatedness, and transmission patterns for better design and evaluation of disease control efforts.

A fair fight between molecular marker types in a seascape genetics setting.

From its inception, population genetics has been nearly as concerned with the genetic data type-to which analyses are brought to bear-as it is with the analysis methods themselves. The field has traversed allozymes, microsatellites, segregating sites in multilocus alignments and, currently, single nucleotide polymorphisms (SNPs) generated by high-throughput genomic sequencing methods, primarily whole genome sequencing and reduced representation library (RRL) sequencing. As each emerging data type has gained traction, it has been compared to existing methods, based on its relative ability to discern population structural complexity at increasing levels of resolution. However, this is usually done by comparing the gold standard in one data type to the gold standard in the new data type. These gold standards frequently differ in power and in sampling density, both across a genome and throughout a spatial range. In this issue of Molecular Ecology, D'Aloia et al. apply the high-throughput approach as fully as possible to microsatellites, nuclear loci and SNPs genotyped through an RRL method; this is coupled with a spatially dense sampling scheme. Completing a battery of population genetics analyses across data types (including a series of down-sampled data sets), the authors find that SNP data are slightly more sensitive to fine-scale genetic structure, and the results are more resilient to down-sampling than microsatellites and nonrepetitive nuclear loci. However, their results are far from an unqualified victory for RRL SNP data over all previous data types: the authors note that modest additions to the microsatellites and nuclear loci data sets may provide the necessary analytical power to delineate the fine-scale genetic structuring identified by SNPs. As always, as the field begins to fully embrace the newest thing, good science reminds us that traditional data types are far from useless, especially when combined with a well-designed sampling scheme.

A phylogenomic framework, evolutionary timeline and genomic resources for comparative studies of decapod crustaceans.

Comprising over 15 000 living species, decapods (crabs, shrimp and lobsters) are the most instantly recognizable crustaceans, representing a considerable global food source. Although decapod systematics have received much study, limitations of morphological and Sanger sequence data have yet to produce a consensus for higher-level relationships. Here, we introduce a new anchored hybrid enrichment kit for decapod phylogenetics designed from genomic and transcriptomic sequences that we used to capture new high-throughput sequence data from 94 species, including 58 of 179 extant decapod families, and 11 of 12 major lineages. The enrichment kit yields 410 loci (greater than 86 000 bp) conserved across all lineages of Decapoda, more clade-specific molecular data than any prior study. Phylogenomic analyses recover a robust decapod tree of life strongly supporting the monophyly of all infraorders, and monophyly of each of the reptant, 'lobster' and 'crab' groups, with some results supporting pleocyemate monophyly. We show that crown decapods diverged in the Late Ordovician and most crown lineages diverged in the Triassic-Jurassic, highlighting a cryptic Palaeozoic history, and post-extinction diversification. New insights into decapod relationships provide a phylogenomic window into morphology and behaviour, and a basis to rapidly and cheaply expand sampling in this economically and ecologically significant invertebrate clade.

Sipunculan larvae and "cosmopolitan" species.

Sipuncula is a relatively small taxon with roughly 150 recognized species. Many species are geographically widespread or "cosmopolitan." The pelagosphera larvae of some species are estimated to spend several months in the plankton. However, recent molecular evidence suggests that many of the "cosmopolitan" species actually represent species-complexes, some not even monophyletic. Herein, we present data on three sipunculan species with different developmental modes that occur both in the Sea of Japan and in the Northeast Pacific. The development of the three species-Phascolosoma agassizii, Thysanocardia nigra, and Themiste pyroides-is exceptionally well studied in both regions of the Pacific. Significant differences have been observed between the two regions with respect to egg size, developmental mode, and developmental timing. In general, eggs are larger and development slower in the Northeast Pacific when compared with the Sea of Japan. These differences have been explained as a result of phenotypic plasticity exhibited under different environmental conditions, in particular temperature, but we show that the populations of all three species are also remarkably distinct genetically and that gene flow between the two regions is extremely unlikely. In Thysanocardia nigra, we even found two very distinct genetic lineages within the same location in the Northeast Pacific. The amount of genetic divergence between populations from the Sea of Japan and those from the Northeast Pacific is not correlated with developmental mode. Themiste pyroides, the species with the most abbreviated development, actually has the least degree of genetic divergence between the regions. Analyses of molecular variance show that the majority of the observed variation in all three species is between the regions. We conclude that all three "cosmopolitan" species actually represent complexes of cryptic or pseudo-cryptic species. These examples demonstrate that a solid taxonomic framework based on molecular and morphological evidence is a prerequisite for evaluating relationships between dispersal capabilities, species' ranges, and the connectivity of populations.