Across herbivorous insect clades, species richness and host-use diversity tend to positively covary. This could be because host-use divergence drives speciation, or because it raises the ecological limits on species richness. To evaluate these hypotheses, we performed phylogenetic path model analyses of the species diversity of Nearctic aphids. Here, we show that variation in the species richness of aphid clades is caused mainly by host-use divergence, whereas variation in speciation rates is caused more by divergence in non-host-related niche variables. Aphid speciation is affected by both the evolution of host and non-host-related niche components, but the former is largely caused by the latter. Thus, our analyses suggest that host-use divergence can both raise the ecological limits on species richness and drive speciation, although in the latter case, host-use divergence tends to be a step along the causal path leading from non-host-related niche evolution to speciation.
To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers. , A mosaic approach to protection The COVID-19 pandemic has been ongoing for more than 2 years now, and new variants such as Omicron are less susceptible to the vaccines developed against earlier lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, there is continued risk of spillovers of other animal sarbecoviruses into humans. There is thus a need for vaccines that will give broader protection. Cohen et al . developed mosaic nanoparticles that display the receptor-binding domains (RBDs) from SARS-CoV-2 and seven other animal sarbecoviruses. Mosaic nanoparticles protected against both SARS-CoV-2 and SARS-CoV challenges in animal models even though the SARS-CoV RBD was not present on the mosaic-8 RBD nanoparticles. By contrast, a homotypic SARS-CoV-2 RBD nanoparticle (presenting only SARS-CoV-2 RBDs) only protected against a SARS-CoV-2 challenge. —VV , A mosaic sarbecovirus nanoparticle protects against SARS-2 and SARS-1, whereas a SARS-2 nanoparticle only protects against SARS-2. , INTRODUCTION Two animal coronaviruses from the severe acute respiratory syndrome (SARS)–like betacoronavirus (sarbecovirus) lineage, SARS coronavirus (SARS-CoV) and SARS-CoV-2, have caused epidemics or pandemics in humans in the past 20 years. SARS-CoV-2 triggered the COVID-19 pandemic that has been ongoing for more than 2 years despite rapid development of effective vaccines. Unfortunately, new SARS-CoV-2 variants, including multiple heavily mutated Omicron variants, have prolonged the COVID-19 pandemic. In addition, the discovery of diverse sarbecoviruses in bats raises the possibility of another coronavirus pandemic. Hence, there is an urgent need to develop vaccines and therapeutics to protect against both SARS-CoV-2 variants and zoonotic sarbecoviruses with the potential to infect humans. RATIONALE To combat future SARS-CoV-2 variants and spillovers of sarbecoviruses threatening global health, we designed nanoparticles that present 60 randomly arranged spike receptor-binding domains (RBDs) derived from the spike trimers of eight different sarbecoviruses (mosaic-8 RBD nanoparticles) to elicit antibodies against conserved and relatively occluded—rather than variable, immunodominant, and exposed—epitopes. The probability of two adjacent RBDs being the same is low for mosaic-8 RBD nanoparticles, a feature chosen to favor interactions with B cells whose bivalent receptors can cross-link between adjacent RBDs to use avidity effects to favor recognition of conserved, but sterically occluded, RBD epitopes. By contrast, nanoparticles that present 60 copies of SARS-CoV-2 RBDs (homotypic RBD nanoparticles) are theoretically more likely to engage B cells with receptors that recognize immunodominant and sterically accessible, but less conserved, RBD epitopes. RESULTS We compared immune responses elicited by mosaic-8 (SARS-CoV-2 RBD plus seven animal sarbecoviruses RBDs) and homotypic (only SARS-CoV-2 RBDs) nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not represented with an RBD on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization produced antisera that showed equivalent neutralization of SARS-CoV-2 variants, including Omicron variants, and protected from both SARS-CoV-2 and SARS-CoV challenges in mice and nonhuman primates (NHPs), whereas homotypic SARS-CoV-2 immunization protected from SARS-CoV-2 challenge but not from SARS-CoV challenge in mice. Epitope mapping of polyclonal antisera by using deep mutational scanning of RBDs demonstrated targeting of conserved epitopes after immunization with mosaic-8 RBD nanoparticles, in contrast with targeting of variable epitopes after homotypic SARS-CoV-2 RBD nanoparticle immunization, which supports the hypothesized mechanism by which mosaic RBD nanoparticle immunization can overcome immunodominance effects to direct production of antibodies against conserved RBD epitopes. Given the recent plethora of SARS-CoV-2 variants that may be arising at least in part because of antibody pressure, a relevant concern is whether more conserved RBD epitopes might be subject to substitutions that would render vaccines and/or monoclonal antibodies targeting these regions ineffective. This scenario seems unlikely because RBD regions conserved between sarbecoviruses and SARS-CoV-2 variants are generally involved in contacts with other regions of spike trimer and therefore less likely to tolerate selection-induced substitutions. CONCLUSION Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers—in particular, highlighting the potential for a mosaic nanoparticle approach to elicit more broadly protective antibody responses than those with homotypic nanoparticle approaches. Mosaic RBD nanoparticle vaccination protects and elicits antibodies against conserved epitopes. Mosaic-8 elicited broader cross-reactive responses than those of homotypic nanoparticles. In a stringent infection model [K18-human angiotensin-converting enzyme 2 (K18-hACE2)], both protected against matched challenge (SARS-CoV-2 Beta), but only mosaic-8 also protected against a mismatch (SARS-CoV). Mosaic-8–immunized NHPs were protected against mismatched SARS-CoV-2 (Delta) and SARS-CoV. Mosaic-8–elicited antibodies predominantly bound conserved epitopes, whereas homotypic-elicited antibodies predominantly bound variable epitopes.
Abstract Animal species differ considerably in their ability to fight off infections. Finding the genetic basis of these differences is not easy, as the immune response is comprised of a complex network of proteins that interact with one another to defend the body against infection. Here, we used population- and comparative genomics to study the evolutionary forces acting on the innate immune system in natural hosts of avian influenza virus (AIV). For this purpose, we used a combination of hybrid capture, next generation sequencing and published genomes to examine genetic diversity, divergence and signatures of selection in 127 innate immune genes at a micro- and macroevolutionary time scale in 26 species of waterfowl. We show across multiple immune pathways (AIV-, toll-like-, and RIG-I like receptors signalling pathways) that genes involved in pathogen detection (i.e. toll-like receptors) and direct pathogen inhibition (i.e. antimicrobial peptides and interferon-stimulated genes), as well as host proteins targeted by viral antagonist proteins (i.e. MAVS) are more likely to be polymorphic, genetically divergent and under positive selection than other innate immune genes. Our results demonstrate that selective forces vary across innate immune signalling pathways in waterfowl, and we present candidate genes that may contribute to differences in susceptibility and resistance to infectious diseases in wild birds, and that may be manipulated by viruses. Our findings improve our understanding of the interplay between host genetics and pathogens, and offer the opportunity for new insights into pathogenesis and potential drug targets.
The Amazonian marsh rat, Holochilus sciureus, is a member of the subfamily Sigmodontinae, the second-largest subfamily of muroid rodents, with 410 species and ca. 84 genera in 12 tribes. This semiaquatic rodent is distributed in South America and is of great economic and epidemiological importance. In this study, we obtained the first mitochondrial genome of the genus Holochilus obtained from a tissue sample associated with a museum voucher specimen. The generated mitogenome sequence of H. sciureus is 16,358 bp length. It comprises a control region and a conserved set of 37 genes encoding for 2 rRNA genes, 22 tRNA genes and 13 protein-coding genes. We conducted a phylogenetic analysis that included H. sciureus and the only five other published mitochondrial genomes of this poorly studied subfamily of rodents.
Full plastome sequences for land plants have become readily accessible thanks to the development of Next Generation Sequencing (NGS) techniques and powerful bioinformatic tools. Despite this vast amount of genomic data, some lineages remain understudied. Full plastome sequences from the highly diverse (>1,500 spp.) subfamily Tillandsioideae (Bromeliaceae, Poales) have been published for only three (i.e., Guzmania , Tillandsia , and Vriesea ) out of 22 currently recognized genera. Here, we focus on core Tillandsioideae, a clade within subfamily Tillandsioideae, and explore the contribution of individual plastid markers and data categories to inform deep divergences of a plastome phylogeny. We generated 37 high quality plastome assemblies and performed a comparative analysis in terms of plastome structure, size, gene content and order, GC content, as well as number and type of repeat motifs. Using the obtained phylogenetic context, we reconstructed the evolution of these plastome attributes and assessed if significant shifts on the evolutionary traits’ rates have occurred in the evolution of the core Tillandsioideae. Our results agree with previously published phylogenetic hypotheses based on plastid data, providing stronger statistical support for some recalcitrant nodes. However, phylogenetic discordance with previously published nuclear marker-based hypotheses was found. Several plastid markers that have been consistently used to address phylogenetic relationships within Tillandsioideae were highly informative for the retrieved plastome phylogeny and further loci are here identified as promising additional markers for future studies. New lineage-specific plastome rearrangements were found to support recently adopted taxonomic groups, including large inversions, as well as expansions and contractions of the inverted repeats. Evolutionary trait rate shifts associated with changes in size and GC content of the plastome regions were found across the phylogeny of core Tillandsioideae.
In the framework of neutral theory of molecular evolution, genes specific to the development and function of eyes in subterranean animals living in permanent darkness are expected to evolve by relaxed selection, ultimately becoming pseudogenes. However, definitive empirical evidence for the role of neutral processes in the loss of vision over evolutionary time remains controversial. In previous studies, we characterized an assemblage of independently-evolved water beetle (Dytiscidae) species from a subterranean archipelago in Western Australia, where parallel vision and eye loss have occurred. Using a combination of transcriptomics and exon capture, we present evidence of parallel coding sequence decay, resulting from the accumulation of frameshift mutations and premature stop codons, in eight phototransduction genes (arrestins, opsins, ninaC and transient receptor potential channel genes) in 32 subterranean species in contrast to surface species, where these genes have open reading frames. Our results provide strong evidence to support neutral evolutionary processes as a major contributing factor to the loss of phototransduction genes in subterranean animals, with the ultimate fate being the irreversible loss of a light detection system.
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