Differential Selection Pressures Research Articles

High functional allelic diversity and copy number in both MHC classes in the common buzzard

BackgroundThe major histocompatibility complex (MHC), which encodes molecules that recognize various pathogens and parasites and initiates the adaptive immune response in vertebrates, is renowned for its exceptional polymorphism and is a model of adaptive gene evolution. In birds, the number of MHC genes and sequence diversity varies greatly among taxa, believed due to evolutionary history and differential selection pressures. Earlier characterization studies and recent comparative studies suggest that non-passerine species have relatively few MHC gene copies compared to passerines. Additionally, comparative studies that have looked at partial MHC sequences have speculated that non-passerines have opposite patterns of selection on MHC class I (MHC-I) and class II (MHC-II) loci than passerines: namely, greater sequence diversity and signals of selection on MHC-II than MHC-I. However, new sequencing technology is revealing much greater MHC variation than previously expected while also facilitating full sequence variant detection directly from genomic data. Our study aims to take advantage of high-throughput sequencing methods to fully characterize both classes and domains of MHC of a non-passerine bird of prey, the common buzzard (Buteo buteo), to test predictions of MHC variation and differential selection on MHC classes.ResultsUsing genetic, genomic, and transcriptomic high-throughput sequencing data, we established common buzzards have at least three loci that produce functional alleles at both MHC classes. In total, we characterize 91 alleles from 113 common buzzard chicks for MHC-I exon 3 and 41 alleles from 125 chicks for MHC-IIB exon 2. Among these alleles, we found greater sequence polymorphism and stronger diversifying selection at MHC-IIB exon 2 than MHC-I exon 3, suggesting differential selection pressures on MHC classes. However, upon further investigation of the entire peptide-binding groove by including genomic data from MHC-I exon 2 and MHC-IIA exon 2, this turned out to be false. MHC-I exon 2 was as polymorphic as MHC-IIB exon 2 and MHC-IIA exon 2 was essentially invariant. Thus, comparisons between MHC-I and MHC-II that included both domains of the peptide-binding groove showed no differences in polymorphism nor diversifying selection between the classes. Nevertheless, selection analysis indicates balancing selection has been acting on common buzzard MHC and phylogenetic inference revealed that trans-species polymorphism is present between common buzzards and species separated for over 33 million years for class I and class II.ConclusionsWe characterize and confirm the functionality of unexpectedly high copy number and allelic diversity in both MHC classes of a bird of prey. While balancing selection is acting on both classes, there is no evidence of differential selection pressure on MHC classes in common buzzards and this result may hold more generally once more data for understudied MHC exons becomes available.

Phylogenetic and comparative genomics establishes origin of paralogy between homologs of AtMYB42 and AtMYB85 in last common ancestor of Brassicaceae via segmental duplication

Origin and evolution of secondary cell wall is considered key to colonization of terrestrial habitat by plants. The primary component of secondary cell wall, lignin, imparts strength and rigidity and enables plants to endure negative pressure created during transpiration. Members of the MYB transcription family, AtMYB42 and AtMYB85, play critical roles as regulators of lignin biosynthesis. Inspite of their functional significance, evolutionary history of homologs of AtMYB42 and AtMYB85 across land plants remains to be investigated. Our analysis revealed that homologs of AtMYB42 and AtMYB85 as two distinct genes are not present in any plant lineage outside Brassicaceae and only the ancestral form exists as AtMYB42/AtMYB85. Analysis of homologs of AtMYB42 and AtMYB85 across green plants combined with comparative genomics, selection pressure, and character-state reconstruction reveals that AtMYB42 and AtMYB85 are paralogous, and arose via segmental duplication, which may coincide with the α-event of WGD that occurred after the split of Brassicaceae-Caricaceae from the last common ancestor. Within Brassicaceae, homeologs and paralogs that arose as a result of polyploidization, and species- and lineage-specific changes could be observed. For instance, homologs of AtMYB42 were found to be deleted from the entire Brassica lineage. Analysis of homeologous segments in neopolyploids (B. napus, B. juncea, Camelina sativa), and meso-polyploid (B. rapa) revealed differential degrees of gene loss and retention. In Brassicaceae, homologs of AtMYB42 were found to be under purifying selection and of AtMYB85 under positive selection. High sequence identity in the coding region between homologs of AtMYB42 and AtMYB85 is indicative of redundant roles, and the loss of homologs of AtMYB42 in Brassica may be compensated by presence of AtMYB85 homologs and homeologs. The study thus forms the basis to investigate questions on regulatory diversification owing to variation in cis-elements between the paralogs and among homeologs, and, impact of differential selection pressure vis-a-vis redundant function.

Being noisy in a crowd: Differential selective pressure on gene expression noise in model gene regulatory networks.

Expression noise, the variability of the amount of gene product among isogenic cells grown in identical conditions, originates from the inherent stochasticity of diffusion and binding of the molecular players involved in transcription and translation. It has been shown that expression noise is an evolvable trait and that central genes exhibit less noise than peripheral genes in gene networks. A possible explanation for this pattern is increased selective pressure on central genes since they propagate their noise to downstream targets, leading to noise amplification. To test this hypothesis, we developed a new gene regulatory network model with inheritable stochastic gene expression and simulated the evolution of gene-specific expression noise under constraint at the network level. Stabilizing selection was imposed on the expression level of all genes in the network and rounds of mutation, selection, replication and recombination were performed. We observed that local network features affect both the probability to respond to selection, and the strength of the selective pressure acting on individual genes. In particular, the reduction of gene-specific expression noise as a response to stabilizing selection on the gene expression level is higher in genes with higher centrality metrics. Furthermore, global topological structures such as network diameter, centralization and average degree affect the average expression variance and average selective pressure acting on constituent genes. Our results demonstrate that selection at the network level leads to differential selective pressure at the gene level, and local and global network characteristics are an essential component of gene-specific expression noise evolution.

Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro.

Dengue virus (DENV) is an arbovirus whose transmission cycle involves disparate hosts: humans and mosquitoes. The error-prone nature of viral RNA replication drives the high mutation rates, and the consequently high genetic diversity affects viral fitness over this transmission cycle. A few studies have been performed to investigate the intrahost genetic diversity between hosts, although their mosquito infections were performed artificially in the laboratory setting. Here, we performed whole-genome deep sequencing of DENV-1 (n = 11) and DENV-4 (n = 13) derived from clinical samples and field-caught mosquitoes from the houses of naturally infected patients, in order to analyze the intrahost genetic diversity of DENV between host types. Prominent differences in DENV intrahost diversity were observed in the viral population structure between DENV-1 and DENV-4, which appear to be associated with differing selection pressures. Interestingly, three single amino acid substitutions in the NS2A (K81R), NS3 (K107R), and NS5 (I563V) proteins in DENV-4 appear to be specifically acquired during infection in Ae. aegypti mosquitoes. Our in vitro study shows that the NS2A (K81R) mutant replicates similarly to the wild-type infectious clone-derived virus, while the NS3 (K107R), and NS5 (I563V) mutants have prolonged replication kinetics in the early phase in both Vero and C6/36 cells. These findings suggest that DENV is subjected to selection pressure in both mosquito and human hosts. The NS3 and NS5 genes may be specific targets of diversifying selection that play essential roles in early processing, RNA replication, and infectious particle production, and they are potentially adaptive at the population level during host switching.

Evolution and phylogenetic diversity of the aquaporin gene family in arachnids

Water flux across cells predominantly occurs through the pore formed by the aquaporin channels. Since water balance is one of the most important challenges to terrestrial animals, aquaporin evolution and diversity is known to play roles in animal terrestrialisation. Arachnids (Arthropoda: Chelicerata: Arachnida) are the second most diverse group and represent the pioneer land colonists in animals; however, there remains no thorough investigation on aquaporin evolution and diversity in this evolutionarily important lineage. Here we reported a phylogenetic study of aquaporin evolution and diversity using genomic data from 116 arachnid species covering almost all (15/16) extant orders. A previously unrecognised subfamily related to aquaporin-4 (i.e. Aqp4-like subfamily) via phylogenetic analysis was identified, suggesting certain underestimate of the arachnid aquaporin diversity in earlier studies probably due to limited taxonomic sampling. Further analysis indicates that this subfamily emerged deep within the life tree of arthropods. Gene tree of another Aqp4-like subfamily (PripL) shows an unexpected basal split between acariform mites (Acariformes) and other arachnids. A closer inspection demonstrated that the PripL evolved quickly and has been under differential selection pressure in acariform mites. Evidence is provided that the evolutionarily ancient Glp subfamily (i.e. aquaglyceroporin) is significantly expanded in terrestrial arachnids compared with their marine relatives. Finally, in spite of the phylogenetic diversity, there exists conservation of some exons in size, functional domain, and intron-insertion phase: an 81-bp and a 218-bp exon, respectively, in apq4-like and glp genes across Eumetazoa lineages including arachnids and human beings. Both exons encode the carboxyl-terminal NPA motif, implying the coding and splicing pressure during hundreds of million years of animal evolution. Hypotheses were tested to explore the possible link between these findings and arachnid terrestrialisation.

Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication

Oncogenic fusions formed through chromosomal rearrangements are hallmarks of childhood cancer that define cancer subtype, predict outcome, persist through treatment, and can be ideal therapeutic targets. However, mechanistic understanding of the etiology of oncogenic fusions remains elusive. Here we report a comprehensive detection of 272 oncogenic fusion gene pairs by using tumor transcriptome sequencing data from 5190 childhood cancer patients. We identify diverse factors, including translation frame, protein domain, splicing, and gene length, that shape the formation of oncogenic fusions. Our mathematical modeling reveals a strong link between differential selection pressure and clinical outcome in CBFB-MYH11. We discover 4 oncogenic fusions, including RUNX1-RUNX1T1, TCF3-PBX1, CBFA2T3-GLIS2, and KMT2A-AFDN, with promoter-hijacking-like features that may offer alternative strategies for therapeutic targeting. We uncover extensive alternative splicing in oncogenic fusions including KMT2A-MLLT3, KMT2A-MLLT10, C11orf95-RELA, NUP98-NSD1, KMT2A-AFDN and ETV6-RUNX1. We discover neo splice sites in 18 oncogenic fusion gene pairs and demonstrate that such splice sites confer therapeutic vulnerability for etiology-based genome editing. Our study reveals general principles on the etiology of oncogenic fusions in childhood cancer and suggests profound clinical implications including etiology-based risk stratification and genome-editing-based therapeutics.

Reproductive effort in two viviparous species of blue-tailed skinks (Squamata: Scincidae: Plestiodon) from Mexico

The relative allocation of energy organisms devote to reproductive processes (aka reproductive effort) constitutes a central topic in life history theory. We document some aspects of the reproductive ecology and investment of 2 viviparous skinks of the genus Plestiodon from Mexico: an undescribed species previously assigned to P. brevirostris(Plestiodon sp., La Malinche, Tlaxcala, 2,700-3,000 m) and P. dugesii (2 populations, Mazamitla and Tapalpa, Jalisco; 2,400-2,500 m). We used relative litter mass (RLM) as a measure of reproductive effort and calculated a body condition index (BCI) as a proxy of the energy status of non-pregnant females, post-parturient females, and neonates. There were no differences in any of the reproductive characteristics between the 2 populations of P. dugesii. Both species lacked sexual size dimorphism, and female body size did not influence RLM, litter size nor litter mass. However, female BCI influenced RLM and, in P. dugesii, a larger litter size correlated with a lower BCI of neonates. Despite their overall similarities in reproductive investment, there seem to be differential selective pressures shaping offspring characteristics of these 2 lizard species.

Population genetics and phylogeography of alfalfa mosaic virus in China and a comparison with other regional epidemics based on the cp gene.

Alfalfa mosaic virus (AMV) is the most pervasive epidemic virus affecting alfalfa production. However, detailed investigations on the molecular population genetics and evolutionary dynamics of AMV are scarce. This study aimed to report on a large-scale long-term survey of genetic variability in AMV populations from China and perform a comparative analysis of AMV population genetics in the three most thoroughly studied countries to date: China, Iran, and Spain. The study was based on the analysis of the coat protein gene (cp) using two analytical approaches: an analysis of molecular variance (AMOVA) and a Bayesian Markov Chain Monte Carlo approach that investigates the association between geographical origin and phylogeny. Both analytical approaches found significant genetic differentiation within localities, but not among localities nor among provinces. This observation might result from inappropriate agronomical practices involving extensive exchange of plant materials followed by rapid viral diversification within localities. In the Chinese population, both methods found that genetic diversification in AMV was strongly associated with different bioclimatic zones. Rates of molecular evolution were similar in the three countries. The estimated epidemic exponential population size and growth rate suggest that the epidemics grew faster and with higher incidence in Iran, followed by Spain and China. Estimates of the time to the most recent common ancestors suggest that AMV was first seen in Spain by the beginning of the twentieth century and later on in eastern and central Eurasia. After ruling out the existence of recombination breakpoints within the cp gene, a codon-based selection analysis per population was performed and identified many codons under significant negative selection and a few under significant positive selection; the latter varied among countries, suggesting regional differences in selective pressures.

Boldness, movement and exploration tendency in round goby (Neogobius melanostomus) in Southern Ontario.

Invasive species have the potential to damage ecosystems outside their native range. At an invasion front, individuals are faced with the unfamiliar conditions of a novel environment. Therefore, certain behavioural traits such as boldness and movement likely play a role in invasion ecology. If behavioural traits of this kind are influenced by differing selection pressures between demographic groups of the same species, this could have broad implications for the management of expanding invasion fronts. To determine whether the invasive round goby (Neogobius melanostomus, Pallas, 1814) exhibits sex- and habitat-based differences in boldness and movement across the invasion front, the authors assessed individual movement and exploration tendency under controlled lab settings using video analysis in a behavioural assay. N. melanostomus from lakes tended to be bolder than those from streams, and females tended to be bolder than males. This study provides evidence for sex- and habitat-based differences in behaviour in this globally invasive species that the authors hope will assist in forming the foundation for contextually appropriate management strategies.

Sexual dimorphism in corallite size and modularity of a broadcast spawning coral, Porites lobata

Differences in selective pressures and the energetic cost of gametes in gonochoristic corals should vary with the sex of the colony, which may lead to sexual dimorphism. Coral colonies are composed of subunits (corallites) that create a complex morphological architecture. If corallite features are distinct between sexes, then the degree of coordinated change among these subunits may also vary (phenotypic modularity). This study tested for sexual dimorphism in the corallites of the reef-building coral Porites lobata, a gonochoric broadcast spawner, and compared this with previously demonstrated sexual dimorphism in its congener P. panamensis, a gonochoric brooder. Corallite area in P. lobata was 17% larger for males than for females (p < 0.05). Phenotypic modularity analysis showed that the integration of skeletal traits differs between sexes in both P. lobata and in P. panamensis. In P. lobata, females showed a higher trait integration than males, while the opposite pattern was observed in P. panamensis. Our results demonstrate corallite traits differentiate between sexes and suggest that between-sex differences in the degree of corallite integration may vary with reproductive mode.

An evolutionary explanation of female-biased sexual size dimorphism in North Sea plaice, Pleuronectes platessa L.

Sexual size dimorphism (SSD) is caused by differences in selection pressures and life-history trade-offs faced by males and females. Proximate causes of SSD may involve sex-specific mortality, energy acquisition, and energy expenditure for maintenance, reproductive tissues, and reproductive behavior. Using a quantitative, individual-based, eco-genetic model parameterized for North Sea plaice, we explore the importance of these mechanisms for female-biased SSD, under which males are smaller and reach sexual maturity earlier than females (common among fish, but also arising in arthropods and mammals). We consider two mechanisms potentially serving as ultimate causes: (a) Male investments in male reproductive behavior might evolve to detract energy resources that would otherwise be available for somatic growth, and (b) diminishing returns on male reproductive investments might evolve to reduce energy acquisition. In general, both of these can bring about smaller male body sizes. We report the following findings. First, higher investments in male reproductive behavior alone cannot explain the North Sea plaice SSD. This is because such higher reproductive investments require increased energy acquisition, which would cause a delay in maturation, leading to male-biased SSD contrary to observations. When accounting for the observed differential (lower) male mortality, maturation is postponed even further, leading to even larger males. Second, diminishing returns on male reproductive investments alone can qualitatively account for the North Sea plaice SSD, even though the quantitative match is imperfect. Third, both mechanisms can be reconciled with, and thus provide a mechanistic basis for, the previously advanced Ghiselin-Reiss hypothesis, according to which smaller males will evolve if their reproductive success is dominated by scramble competition for fertilizing females, as males would consequently invest more in reproduction than growth, potentially implying lower survival rates, and thus relaxing male-male competition. Fourth, a good quantitative fit with the North Sea plaice SSD is achieved by combining both mechanisms while accounting for sex-specific costs males incur during their spawning season. Fifth, evolution caused by fishing is likely to have modified the North Sea plaice SSD.

Evolutionary and structural aspects of Solanaceae RNases T2.

Plant RNases T2 are involved in several physiological and developmental processes, including inorganic phosphate starvation, senescence, wounding, defense against pathogens, and the self-incompatibility system. Solanaceae RNases form three main clades, one composed exclusively of S-RNases and two that include S-like RNases. We identified several positively selected amino acids located in highly flexible regions of these molecules, mainly close to the B1 and B2 substrate-binding sites in S-like RNases and the hypervariable regions of S-RNases. These differences between S- and S-like RNases in the flexibility of amino acids in substrate-binding regions are essential to understand the RNA-binding process. For example, in the S-like RNase NT, two positively selected amino acid residues (Tyr156 and Asn134) are located at the most flexible sites on the molecular surface. RNase NT is induced in response to tobacco mosaic virus infection; these sites may thus be regions of interaction with pathogen proteins or viral RNA. Differential selective pressures acting on plant ribonucleases have increased amino acid variability and, consequently, structural differences within and among S-like RNases and S-RNases that seem to be essential for these proteins play different functions.

The tempo and mode of character evolution in the assembly of mimetic communities

Multitrait adaptive evolution is shaped by factors such as phylogenetic and functional constraints as well as the intensity and direction of selection. The tempo and mode of such multitrait evolution can differentially impact the assembly of biological communities. Batesian mimicry, in which undefended prey gain a fitness advantage by evolving a resemblance to aposematic models, involves adaptive evolution of multiple traits such as color patterns and flight morphology. To elucidate the evolutionary mechanisms of such multitrait adaptations, we evaluated the tempo and mode of adaptive convergence in flight morphology and color patterns in mimetic butterfly communities. We found that compared with Batesian mimics or nonmimetic sister species, models showed significantly faster rates of aposematic trait evolution, creating adaptive peaks for mimicry. At the community level, the degree of mimetic resemblance between mimics and models was positively correlated with the rate of character evolution, but independent of phylogenetic relatedness. Monomorphic mimics and female-limited mimics converged on the color patterns of models to a similar degree, showing that there were no constraints on mimetic trait evolution with respect to sex-specific selections. Convergence was driven by the greater lability of color patterns, which evolved at significantly faster rates than the phylogenetically conserved flight morphological traits, indicating that the two traits evolve under differential selection pressures and/or functional and genetic constraints. These community-wide patterns show that during the assembly of a community, the tempo of adaptive evolution is nonlinear, and specific to the underlying functional relationships and key traits that define the community.

Ancient vicariance is reinforced by adaptive divergence in the southern beech: Contributions from geogenomics

AbstractAimGeogenomics seeks to understand geological processes linked to lineage divergence. However, the mechanisms that conserve ancient signals in spite of gene flow are still unclear. In the southern beech, the deep lineage divergence produced by vicariant events is associated with ancient marine transgressions. We hereby evaluate the hypothesis that this divergence is maintained by diversifying selection.LocationSouthern Argentina and Chile.Taxon Nothofagus dombeyi. MethodsThe lineage divergence by means of analysis of molecular variance (AMOVA), principal coordinate analysis, assignment tests and multiple matrix regression analyses were assessed using chloroplast DNA and neutral and outlier single nucleotide polymorphisms (SNPs). Several environmental variables were used to characterize potential within‐species niche structuring and genotype–environment associations.ResultsTwo deep‐rooted latitudinally structured lineages resulted from cpDNA, the northern cluster being more genetically diverse than the southern one. Of the total of 2943 SNPs, 33 identified as outliers and produced two genetic clusters. Neutral SNPs yielded no structure by AMOVA, whereas higher (>75%) FST values were obtained for cpDNA and outlier SNPs. Precipitation variables were mostly associated with population clusters and suggested two climatic niches, consisting of cold and dry in the south and more variable precipitation, temperature and soil conditions in the north. Associations of genetic distance with environment and geography suggested isolation‐by‐distance and isolation‐by‐ecology or isolation‐by‐environment effects.Main conclusionsAncient lineage divergence in N. dombeyi, originally driven by vicariance, has been maintained by diversifying selection under distinct environmental conditions that also define distinct within‐species niches. Deeply rooted phylogeographical breaks can be conserved in continuously distributed species in the absence of current geographical barriers. Yet, physical gradients exert differential selective pressures, which are maintained in the face of potential gene flow. As a result, selection can lead to geographically localized and differentially adapted groups of populations that can be detected by a combination of traditional phylogeographical and novel genomic methods.

Phenotypic traits evolution and morphological traits associated with echolocation calls in cryptic horseshoe bats (Rhinolophidae)

AbstractBats provide an excellent casestudy for studying evolution due to their remarkable flight and echolocation capabilities. In this study, we sought to understand the phenotypic evolution of key traits in Rhinolophidae (horseshoe bats) using phylogenetic comparative methods. We aimed to test the phylogenetic signals of traits, and evaluated the best‐fit evolutionary models given the data for each trait considering different traits may evolve under different models (i.e., Brownian Motion [BM], Ornstein‐Uhlenbeck [OU], and Early Burst [EB]) and reconstruct ancestral character states. We examined how phenotypic characters are associated with echolocation calls and minimum detectable prey size. We measured 34 traits of 10 Asian rhinolophids species (187 individuals). We found that the majority of traits showed a high phylogenetic signal based on Blomberg′s K and Pagel′s λ, but each trait may evolve under different evolutionary models. Sella traits were shown to evolve under stabilizing selection based on OU models, indicating sella traits have the tendency to move forward along the branches toward some medial value in equilibrium. Our findings highlight the importance of sella characters in association with echolocation call emissions in Rhinolophidae, as calls are important for spatial cognition and also influence dietary preferences. Minimum detectable prey size in Rhinolophidae was associated with call frequency, bandwidth, call duration, wingspan, and wing surface area. Ultimately, understanding trait evolution requires sensitivity due to the differential selective pressures which may apply to different characteristics.

Floral trait variation across individual plants within a population enhances defense capability to nectar robbing

Floral trait variation may help pollinators and nectar robbers identify their target plants and, thus, lead to differential selection pressure for defense capability against floral antagonists. However, the effect of floral trait variation among individuals within a population on multi-dimensional plant-animal interactions has been little explored. We investigated floral trait variation, pollination, and nectar robbing among individual plants in a population of the bumble bee-pollinated plant, Caryopteris divaricata, from which flowers are also robbed by bumble bees with varying intensity across individuals. We measured the variation in corolla tube length, nectar volume and sugar concentration among individual plants, and evaluated whether the variation were recognized by pollinators and robbers. We investigated the influence of nectar robbing on legitimate visitation and seed production per fruit. We found that the primary nectar robber (Bombus nobilis) preferred to forage on plants with long-tubed flowers, which produced less nectar and had lower sugar concentration compared to those with shorter corolla tubes. Individuals with shorter corolla tubes had comparatively lower nectar robbing intensity but higher visitation by legitimate visitors (mainly B. picipes) and higher seed production. Nectar robbing significantly reduced seed production because it decreased pollinator visits. However, neither pollination nor seed production differed between plants with long and short corolla tubes when nectar robbers were excluded. This finding suggests that floral trait variation might not be driven by pollinators. Such variation among individual plants thus allows legitimate visitors and nectar robbers to segregate niches and enhances population defense against nectar robbing in unpredictable conditions.

In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics.

New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron's spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome.

Potential drivers for schistosomiasis persistence: Population genetic analyses from a cluster-randomized urogenital schistosomiasis elimination trial across the Zanzibar islands.

The World Health Organization's revised NTD Roadmap and the newly launched Guidelines target elimination of schistosomiasis as a public health problem in all endemic areas by 2030. Key to meeting this goal is elucidating how selective pressures imposed by interventions shape parasite populations. Our aim was to identify any differential impact of a unique cluster-randomized tri-armed elimination intervention (biannual mass drug administration (MDA) applied alone or in association with either mollusciciding (snail control) or behavioural change interventions) across two Zanzibarian islands (Pemba and Unguja) on the population genetic composition of Schistosoma haematobium over space and time. Fifteen microsatellite loci were used to analyse individual miracidia collected from infected individuals across islands and intervention arms at the start (2012 baseline: 1,522 miracidia from 176 children; 303 from 43 adults; age-range 6-75, mean 12.7 years) and at year 5 (2016: 1,486 miracidia from 146 children; 214 from 25 adults; age-range 9-46, mean 12.4 years). Measures of genetic diversity included allelic richness (Ar), Expected (He) and Observed heterozygosity (Ho), inbreeding coefficient (FST), parentage analysis, estimated worm burden, worm fecundity, and genetic sub-structuring. There was little evidence of differential selective pressures on population genetic diversity, inbreeding or estimated worm burdens by treatment arm, with only the MDA+snail control arm within Unguja showing trends towards reduced diversity and altered inbreeding over time. The greatest differences overall, both in terms of parasite fecundity and genetic sub-structuring, were observed between the islands, consistent with Pemba's persistently higher mean infection intensities compared to neighbouring Unguja, and within islands in terms of infection hotspots (across three definitions). These findings highlight the important contribution of population genetic analyses to elucidate extensive genetic diversity and biological drivers, including potential gene-environmental factors, that may override short term selective pressures imposed by differential disease control strategies. Trial Registration: ClinicalTrials.gov ISRCTN48837681.

Reproductive senescence in polar bears in a variable environment

Reproductive senescence is ubiquitous in mammals. However, patterns of senescence vary across reproductive traits, even within populations, perhaps because of differences in selection pressures, physiological constraints, and responses to environmental conditions. We investigated reproductive senescence in wild female polar bears (Ursus maritimus), using 31 years of capture-recapture data from the Svalbard area. We studied the influence of environmental conditions on age-specific litter production and litter size using generalized linear mixed models. Further, using a capture-recapture model that handles the dependency between vital rates of individuals belonging to the same family unit, we assessed maternal-age-related changes in first year cub and litter survival. We provide clear evidence for reproductive senescence in female polar bears. Litter production and litter size peaked in middle-aged females and declined sharply afterward. By contrast cub and litter survival did not decline after prime age. We found no evidence of terminal investment. The reproductive output of all females was affected by sea-ice conditions during the previous year and the Arctic Oscillation, with some effects differing greatly between age groups. Old females were affected the most by environmental conditions. Our results suggest that the decline in reproductive output is a combination of fertility and body-condition senescence, with a weak contribution of maternal-effect senescence, possibly due to benefits of experience. Further, as predicted by evolutionary theory, senescence appears to be a consequence of failures in early stages of the reproductive cycle rather than in late stages, and environmental variation affected old females more than prime-aged females. Our study emphasizes the need to study several reproductive traits and account for environmental variation when investigating reproductive senescence. Differences in senescence patterns across reproductive traits should be interpreted in light of evolutionary theory and while considering underlying physiological drivers.

Analysis of the ASR and LP3 homologous gene families reveal positive selection acting on LP3-3 gene

Drought has long been established as a major environmental stress for plants which have in turn developed several coping strategies, ranging from physiological to molecular mechanisms. LP3 that was first discovered in loblolly pine (Pinus taeda L.) is a homolog of the Abscisic Acid, Stress and Ripening (ASR) gene belonging to the ABA/WDS gene family that was first detected in tomato. LP3 has been shown to be present in four different paralogs in loblolly pine called LP3-0, LP3-1, LP3-2 and LP3-3. LP3 in loblolly pine has not been as extensively studied as the ASR in tomato. Similar to ASR, the different LP3 paralogs have been shown to be upregulated in response to water deficit stress and to act as transcription factors for genes likely involved in hexose transport. In the current study, we have investigated the evolutionary history of LP3 gene family, with the aim of relating it to that of ASR from a phylogenetic perspective and comparing the differences in selective pressure and codon usage. Phylogenetic trees revealed that LP3 is less divergent across species than ASR even when the trees were solely based on the different sub-sections of the gene. Phylogenetic, GC content, codon usage and selective pressure analyses suggest that LP3-3 is undergoing positive selection.