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Background Head lice, Pediculus humanus capitis, occur in four divergent mitochondrial clades (A, B, C and D), each having particular geographical distributions. Recent studies suggest that head lice, as is the case of body lice, can act as a vector for louse-borne diseases. Therefore, understanding the genetic diversity of lice worldwide is of critical importance to our understanding of the risk of louse-borne diseases. Methodology/Principal Findings Here, we report the results of the first molecular screening of pygmies’ head lice in the Republic of Congo for seven pathogens and an analysis of lice mitochondrial clades. We developed two duplex clade-specific real-time PCRs and identified three major mitochondrial clades: A, C, and D indicating high diversity among the head lice studied. We identified the presence of a dangerous human pathogen, Borrelia recurrentis, the causative agent of relapsing fever, in ten clade A head lice, which was not reported in the Republic of Congo, and B. theileri in one head louse. The results also show widespread infection among head lice with several species of Acinetobacter. A. junii was the most prevalent, followed by A. ursingii, A. baumannii, A. johnsonii, A. schindleri, A. lwoffii, A. nosocomialis and A. towneri. Conclusions/Significance Our study is the first to show the presence of B. recurrentis in African pygmies’ head lice in the Republic of Congo. This study is also the first to report the presence of DNAs of B. theileri and several species of Acinetobacter in human head lice. Further studies are needed to determine whether the head lice can transmit these pathogenic bacteria from person to another., Author Summary Head lice, Pediculus capitis humanus, and body lice, Pediculus h. humanus, are obligatory ectoparasites that feed exclusively on human blood. Currently, the body louse is the only recognized vector of at least three deadly bacterial pathogens that have killed millions of peoples, namely: Rickettsia prowazekii, Bartonella quintana and Borrelia recurrentis, responsible for epidemic typhus, trench fever and relapsing fever, respectively. In this work, we aimed to study the genetic diversity of head lice collected from African Pygmies in the Republic of Congo and to look for louse-borne pathogens in these lice. We detected B. recurrentis in head lice belonged to clade A that is prevalent in the Republic of Congo. Our study also show, for the first time, the presence of DNAs of B. theileri and several species of Acinetobacter in human head lice. Despite several investigations into the transmissibility of numerous infectious agents, no conclusive evidence has demonstrated the transmission of disease by head lice. That said, we believe that pathogens detected in head lice may be an indirect tool for evaluating the risk of louse-borne diseases in humans.

The Mediterranean coastline is a dynamic and complex system which owes its complexity to its past and present vicissitudes, e.g. complex tectonic history, climatic fluctuations, and prolonged coexistence with human activities. A plant species that is widespread in this habitat is the sea daffodil, Pancratium maritimum (Amaryllidaceae), which is a perennial clonal geophyte of the coastal sands of the Mediterranean and neighbouring areas, well adapted to the stressful conditions of sand dune environments. In this study, an integrated approach was used, combining genetic and environmental data with a niche modelling approach, aimed to investigate: (1) the effect of climate change on the geographic range of this species at different times {past (last inter-glacial, LIG; and last glacial maximum, LGM), present (CURR), near-future (FUT)} and (2) the possible influence of environmental variables on the genetic structure of this species in the current period. The genetic results show that 48 sea daffodil populations (867 specimens) display a good genetic diversity in which the marginal populations (i.e. Atlantic Sea populations) present lower values. Recent genetic signature of bottleneck was detected in few populations (8%). The molecular variation was higher within the populations (77%) and two genetic pools were well represented. Comparing the different climatic simulations in time, the global range of this plant increased, and a further extension is foreseen in the near future thanks to projections on the climate of areas currently—more temperate, where our model suggested a forecast for a climate more similar to the Mediterranean coast. A significant positive correlation was observed between the genetic distance and Precipitation of Coldest Quarter variable in current periods. Our analyses support the hypothesis that geomorphology of the Mediterranean coasts, sea currents, and climate have played significant roles in shaping the current genetic structure of the sea daffodil especially during LGM because of strong variation in coastline caused by glaciations.

This study aims at establishing specimens pooling approach for the detection of SARS-CoV-2 using the RT-PCR BGI and Sansure-Biotech kits used in Gabon. To validate this approach, 14 positive samples, stored at -20°C for three to five weeks were analyzed individually (as gold standard) and in pools of five, eight and ten in the same plate. We created 14 pools of 5, 8 and 10 samples using 40 μL from each of the selected positive samples mixed with 4, 7 and 9 confirmed negative counterparts in a total volume of 200 μL, 320 μL and 400 μL for the pools of 5, 8 and 10 respectively. Both individual and pooled samples testing was conducted according to the BGI and Sansure-Biotech RT-PCR protocols used at the Professor Daniel Gahouma Laboratory (PDGL). Furthermore, the pooling method was also tested by comparing results of 470 unselected samples tested in 94 pools and individually. Results of our experiment showed that using a BGI single positive sample with cycle threshold (Ct) value of 28.42, confirmed by individual testing, detection occurred in all the pools. On the contrary samples with Ct >31 were not detected in pools of 10 and for these samples (Ct value as high as 37.17) their detection was possible in pool of 8. Regarding the Sansure-Biotech kit, positive samples were detected in all the pool sizes tested, irrespective of their Ct values. The specificity of the pooling method was 100% for the BGI and Sansure-Biotech RT-PCR assays. The present study found an increase in the Ct values with pool size for the BGI and Sansure-Biotech assays. This trend was statistically significant (Pearson’s r = 0.978; p = 0,022) using the BGI method where the mean Ct values were 24.04±1.1, 26.74±1.3, 27.91±1.1 and 28.32±1.1 for the individual, pool of 5, 8 and 10 respectively. The testing of the 470 samples showed that one of the 94 pools had a positive test similar to the individual test using the BGI and Sansure-Biotech kits. The saving of time and economizing test reagents by using the pooling method were demonstrated in this study. Ultimately, the pooling method could be used for the diagnosis of SARS-CoV-2 without modifying the accuracy of results in Gabon. We recommend a maximum pool size of 8 for the BGI kit. For the Sansure-Biotech kit, a maximum pool size of 10 can be used without affecting its accuracy compared to the individual testing.

Evolutionary computing (EC) is an area of computer sciences and applied mathematics covering heuristic optimization algorithms inspired by evolution in Nature. EC extensively study all the variety of methods which were originally based on the principles of selectionism. As a result, many new algorithms and approaches, significantly more efficient than classical selectionist schemes, were found. This is especially true for some families of special problems. There are strong arguments to believe that EC approaches are quite suitable for modeling and numerical analysis of those methods of synthetic biology and biotechnology that are known as in vitro evolution. Therefore, it is natural to expect that the new algorithms and approaches developed in EC can be effectively applied in experiments on the directed evolution of biological macromolecules. According to the John Holland’s Schema theorem, the effective evolutionary search in genetic algorithms (GA) is provided by identifying short schemata of high fitness which in the further search recombine into the larger building blocks (BBs) with higher and higher fitness. The multimodularity of functional biological macromolecules and the preservation of already found modules in the evolutionary search have a clear analogy with the BBs in EC. It seems reasonable to try to transfer and introduce the methods of EC, preserving BBs and essentially accelerating the search, into experiments on in vitro evolution. We extend the key instrument of the Holland’s theory, the Royal Roads fitness function, to problems of the in vitro evolution (Biological Royal Staircase, BioRS, functions). The specific version of BioRS developed in this publication arises from the realities of experimental evolutionary search for (DNA-) RNA-devices (aptazymes). Our numerical tests showed that for problems with the BioRS functions, simple heuristic algorithms, which turned out to be very effective for preserving BBs in GA, can be very effective in in vitro evolution approaches. We are convinced that such algorithms can be implemented in modern methods of in vitro evolution to achieve significant savings in time and resources and a significant increase in the efficiency of evolutionary search.

The effective population size (Ne) is a key parameter to quantify the magnitude of genetic drift and inbreeding, with important implications in human evolution. The increasing availability of high-density genetic markers allows the estimation of historical changes in Ne across time using measures of genome diversity or linkage disequilibrium between markers. Directional selection is expected to reduce diversity and Ne, and this reduction is modulated by the heterogeneity of the genome in terms of recombination rate. Here we investigate by computer simulations the consequences of selection (both positive and negative) and recombination rate heterogeneity in the estimation of historical Ne. We also investigate the relationship between diversity parameters and Ne across the different regions of the genome using human marker data. We show that the estimates of historical Ne obtained from linkage disequilibrium between markers (NeLD) are virtually unaffected by selection. In contrast, those estimates obtained by coalescence mutation-recombination-based methods can be strongly affected by it, which could have important consequences for the estimation of human demography. The simulation results are supported by the analysis of human data. The estimates of NeLD obtained for particular genomic regions do not correlate, or they do it very weakly, with recombination rate, nucleotide diversity, proportion of polymorphic sites, background selection statistic, minor allele frequency of SNPs, loss of function and missense variants and gene density. This suggests that NeLD measures mainly reflect demographic changes in population size across generations., Author summary The inference of the demographic history of populations is of great relevance in evolutionary biology. This inference can be made from genomic data using coalescence methods or linkage disequilibrium methods. However, the assessment of these methods is usually made assuming neutrality (absence of selection). Here we show by computer simulations and analyses of human data that the estimates of historical effective population size obtained from linkage disequilibrium between markers are virtually unaffected by natural selection, either positive or negative. In contrast, estimates obtained by coalescence mutation-recombination-based methods can be strongly affected by it, which could have important consequences for recent estimations of human demography.

Sequencing large numbers of individual samples is often needed for countrywide antimalarial drug resistance surveillance. Pooling DNA from several individual samples is an alternative cost and time saving approach for providing allele frequency (AF) estimates at a population level. Using 100 individual patient DNA samples of dried blood spots from a 2017 nationwide drug resistance surveillance study in Haiti, we compared codon coverage of drug resistance-conferring mutations in four Plasmodium falciparum genes (crt, dhps, dhfr, and mdr1), for the same deep sequenced samples run individually and pooled. Samples with similar real-time PCR cycle threshold (Ct) values (+/- 1.0 Ct value) were combined with ten samples per pool. The sequencing success for samples in pools were higher at a lower parasite density than the individual samples sequence method. The median codon coverage for drug resistance-associated mutations in all four genes were greater than 3-fold higher in the pooled samples than in individual samples. The overall codon coverage distribution for pooled samples was wider than the individual samples. The sample pools with < 40 parasites/μL blood showed more discordance in AF calls for dhfr and mdr1 between the individual and pooled samples. This discordance in AF estimation may be due to low amounts of parasite DNA, which could lead to variable PCR amplification efficiencies. Grouping samples with an estimated ≥ 40 parasites/μL blood prior to pooling and deep sequencing yielded the expected population level AF. Pooling DNA samples based on estimates of > 40 parasites/μL prior to deep sequencing can be used for rapid genotyping of a large number of samples for these four genes and possibly other drug resistant markers in population-based studies. As Haiti is a low malaria transmission country with very few mixed infections and continued chloroquine sensitivity, the pooled sequencing approach can be used for routine national molecular surveillance of resistant parasites.

Background Non-small cell lung cancer (NSCLC) is the most common cancer type in China. Targeted therapies have been used to treat NSCLC for two decades, which is only suitable for a subgroup of patients with specific genetic variations. The aim of this study was to investigate the prevalence of genetic variations leading to sensitivity or resistance to targeted therapies in NSCLC, and their relationship with clinicopathological characteristics of the patients. Methods Tumor samples were collected from 404 patients who were diagnosed to have NSCLC and underwent surgery, transthoracic biopsy, bronchoscopy biopsy, or pleural aspiration in Sichuan Provincial People’s Hospital from January 2019 to March 2020. Commercial amplification-refractory mutation system kits were used to detect targeted therapy-related genetic variations in those tumor samples. The prevalence of genetic variations and their relationship with patient clinicopathological characteristics were analyzed using statistical software, followed by subgroup analysis. Results In all, 50.7% of the NSCLC patients had sensitive genetic variations to anti-EGFR therapies, and 4.9% of those patients had co-existing resistant genetic variations. Fusions in ALK, ROS1, or RET were found in 7.7% of the patients, including 2 patients with co-existing EGFR exon 19 deletion or L858R. EGFR exon 19 deletion and L858R were more common in female patients and adenocarcinoma. Further subgroup analysis confirmed the observation in female patients in adenocarcinoma subgroup, and in adenocarcinoma in male patients. In addition, smokers were more likely to have squamous cell carcinoma and KRAS mutation and less likely to have EGFR L858R, which were also confirmed after standardization of gender except KRAS mutations. Conclusion Nearly half of the NSCLC patients were eligible for anti-EGFR treatments. In NSCLC, female gender and adenocarcinoma may indicate higher chance of EGFR exon 19 deletion or L858R, and smoking history may indicate squamous cell carcinoma and EGFR L858R.

SARS-CoV-2 pandemic has forced frequent testing of populations. It is necessary to identify the most cost-effective strategies for the detection of COVID-19 outbreaks. Nasopharyngeal samples have been used for SARS-CoV-2 detection but require a healthcare professional to collect the sample and cause discomfort and pain to the individual. Saliva has been suggested as an appropriate fluid for the diagnosis of COVID-19. We have investigated the possibility of using pools of saliva samples to detect SARS-CoV-2 in symptomatic and asymptomatic patients. Two hundred and seventy-nine saliva samples were analyzed through RT-PCR of Envelope, Nucleocapsid and Open Reading Frame 1ab genes. Reproducibility assays showed an almost perfect agreement as well as high sensitivity (96.6%), specificity (96.8%), positive predicted value (96.6%), and negative predicted value (96.8%). The average Cycle Threshold of the genes detected was 29.7. No significant differences (p > 0.05) were detected when comparing the cycle threshold average of two consecutive reactions on the same positive saliva samples. Saliva samples have a higher median viral load (32.6) than in nasopharyngeal samples (28.9), although no significant differences were detected (p > 0.05). Saliva-pool samples allowed effective SARS-CoV-2 screening, with a higher sensibility (96.9%) on 10-sample pools than in 20-sample pools (87.5%). Regardless of pools size specificity was high (99.9%) and an almost perfect agreement was observed. Our strategy was successfully applied in population wide testing of more than 2000 individuals, showing that it is possible to use pooled saliva as diagnostic fluid for SARS-CoV-2 infection.

Due to the lack of visible barriers to gene flow, it was a long-standing assumption that marine coastal species are widely distributed, until molecular studies revealed geographically structured intraspecific genetic differentiation in many taxa. Historical events of sea level changes during glacial periods are known to have triggered sequential disjunctions and genetic divergences among populations, especially of coastal organisms. The Parasesarma bidens species complex so far includes three named plus potentially cryptic species of estuarine brachyuran crabs, distributed along East to Southeast Asia. The aim of the present study is to address phylogeography and uncover real and hidden biological diversity within this complex, by revealing the underlying genetic structure of populations and species throughout their distribution ranges from Japan to West Papua, with a comparison of mitochondrial COX1 and 16S rRNA gene sequences. Our results reveal that the P. bidens species complex consists of at least five distinct clades, resulting from four main cladogenesis events during the mid to late Pleistocene. Among those clades, P. cricotum and P. sanguimanus are recovered as monophyletic taxa. Geographically restricted endemic clades are encountered in southeastern Indonesia, Japan and China respectively, whereas the Philippines and Taiwan share two clades. As individuals of the Japanese clade can also be found in Taiwan, we provide evidence of a third lineage and the occurrence of a potential cryptic species on this island. Ocean level retreats during Pleistocene ice ages and present oceanic currents appear to be the main triggers for the divergences of the five clades that are here addressed as the P. bidens complex. Secondary range expansions converted Taiwan into the point of maximal overlap, sharing populations with Japan and the Philippines, but not with mainland China.

In many countries a second wave of infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred, triggering a shortage of reagents needed for diagnosis and compromising the capacity of laboratory testing. There is an urgent need to develop methods to accelerate the diagnostic procedures. Pooling samples represents a strategy to overcome the shortage of reagents, since several samples can be tested using one reaction, significantly increasing the number and speed with which tests can be carried out. We have reported the feasibility to use a direct lysis procedure of saliva as source for RNA to SARS-CoV-2 genome detection by reverse transcription quantitative-PCR (RT-qPCR). Here, we show that the direct lysis of saliva pools, of either five or ten samples, does not compromise the detection of viral RNA. In addition, it is a sensitive, fast, and inexpensive method that can be used for massive screening, especially considering the proximity of the reincorporation of activities in universities, offices, and schools.

Poeciliopsis (Cyprinodontiformes: Poeciliidae) is a genus comprised of 25 species of freshwater fishes. Several well-known taxonomic uncertainties exist within the genus, especially in relation to the taxonomic status of Poeciliopsis pleurospilus and P. gracilis. However, to date, no studies have been conducted to specifically address the taxonomic status of these two species. The goal of this study was to examine the taxonomic validity of P. pleurospilus and P. gracilis using genomic data (ddRADseq) in phylogenetic, population genetic, and species delimitation frameworks. Multiple analyses support the recognition of both taxa as distinct species and also permits us to revise their respective distributions. A species delimitation analysis indicates that P. pleurospilus and P. gracilis are distinct species, each of which consists of two distinct lineages that are geographically structured. Phylogenetic and population genetic analyses provide clear evidence that individuals of P. gracilis are distributed north and west of the Isthmus of Tehuantepec in both Pacific and Atlantic river systems in Mexico, whereas individuals of P. pleurospilus are distributed in both Atlantic and Pacific river systems south and east of the Isthmus of Tehuantepec, from southern Mexico to Honduras.

Vigna stipulacea (Lam.) Kuntz., commonly known as Minni payaru is an underutilized legume species and has a great potential to be utilized as food crop. To evaluate and select the best germplasm to be harnessed in the breeding programme, we assessed the genetic diversity of V. stipulacea (94 accessions) conserved in the Indian National Genebank, based on morphological traits and microsatellite markers. Significant variation was recorded for the morphological traits studied. Euclidean distance using UPGMA method grouped all accessions into two major clusters. Accessions were identified for key agronomic traits such as, early flowering (IC331436, IC251436, IC331437); long peduncle length (IC553518, IC550531, IC553557, IC553540, IC550532, IC553564); and more number of seeds per pod (IC553529, IC622865, IC622867, IC553528). To analyse the genetic diversity among the germplasm 33 SSR primers were used anda total of 116 alleles were detected. The number of alleles varied from two to seven, with an average of 3.52 per loci. The polymorphic information content values varied from 0.20 to 0.74, with a mean of 0.40. The high number of alleles per locus and the allelic diversity in the studied germplasm indicated a relatively wider genetic base of V. stipulacea. Phylogenetic analysis clustered accessions into seven clades. Population structure analysis grouped them into five genetic groups, which were partly supported by PCoA and phylogenetic tree. Besides, PCoA and AMOVA also decoded high genetic diversity among the V. stipulacea accessions. Thus, morphological and microsatellite markers distinguished V. stipulacea accessions and assessed their genetic diversity efficiently. The identified promising accessions can be utilized in Vigna improvement programme through introgression breeding and/or can be used for domestication and enhanced utilization of V. stipulacea.

Lévy flight is a type of random walk that characterizes the behaviour of many natural phenomena studied across a multiplicity of academic disciplines; within biology specifically, the behaviour of fish, birds, insects, mollusks, bacteria, plants, slime molds, t-cells, and human populations. The Lévy flight foraging hypothesis states that because Lévy flights can maximize an organism’s search efficiency, natural selection should result in Lévy-like behaviour. Empirical and theoretical research has provided ample evidence of Lévy walks in both extinct and extant species, and its efficiency across models with a diversity of resource distributions. However, no model has addressed the maintenance of Lévy flight foraging through evolutionary processes, and existing models lack ecological breadth. We use numerical simulations, including lineage-based models of evolution with a distribution of move lengths as a variable and heritable trait, to test the Lévy flight foraging hypothesis. We include biological and ecological contexts such as population size, searching costs, lifespan, resource distribution, speed, and consider both energy accumulated at the end of a lifespan and averaged over a lifespan. We demonstrate that selection often results in Lévy-like behaviour, although conditional; smaller populations, longer searches, and low searching costs increase the fitness of Lévy-like behaviour relative to Brownian behaviour. Interestingly, our results also evidence a bet-hedging strategy; Lévy-like behaviour reduces fitness variance, thus maximizing geometric mean fitness over multiple generations., Author summary In heterotrophs, incuding animals, survival depends on the net energy gained through foraging. The expectation, then, is that natural selection results in adaptations for efficient foraging that optimize the balance of searching costs and rewards. Lévy flight foraging has been proposed as an optimal foraging solution. The hypothesis states, if no information about resource locations are available, and the locations are re-visitable, then selection will result in adaptations for Lévy flight foraging, a type of random walk. It has been argued that Levy-like foraging behaviour may simply reflect how resources are distributed, but empirical and theoretical research suggests that this behaviour is intrinsic or innate. However, this research does not address evolutionary mechanisms, and lacks ecological breadth. We extend the current theoretical framework by including evolutionary ecological contexts. We treat an organism’s random walk as a heritable trait, and explore ecological contexts such as population size, lifespan, carrying capacity, searching costs, reproductive strategies, and different distributions of food. Our evolutionary simulations overwhelmingly resulted in selection for Lévy-like foraging, regardless of the distribution of food, and evidences Lévy flight foraging as a bet-hedging strategy. Thus, here we provide some of the first evidence for the evolutionary maintenance of Lévy flight foraging.

It is well documented that drug responses are related to Absorption, Distribution, Metabolism, and Excretion (ADME) characteristics of individual patients. Several studies have identified genetic variability in pharmacogenes, that are either directly responsible for or are associated with ADME, giving rise to individualized treatments. Our objective was to provide a comprehensive overview of pharmacogenetic variation in the Saudi population. We mined next generation sequencing (NGS) data from 11,889 unrelated Saudi nationals, to determine the presence and frequencies of known functional SNP variants in 8 clinically relevant pharmacogenes (CYP2C9, CYP2C19, CYP3A5, CYP4F2, VKORC1, DPYD, TPMT and NUDT15), recommended by the Clinical Pharmacogenetics Implementation Consortium (CPIC), and collectively identified 82 such star alleles. Functionally significant pharmacogenetic variants were prevalent especially in CYP genes (excluding CYP3A5), with 10–44.4% of variants predicted to be inactive or to have decreased activity. In CYP3A5, inactive alleles (87.5%) were the most common. Only 1.8%, 0.7% and 0.7% of NUDT15, TPMT and DPYD variants respectively, were predicted to affect gene activity. In contrast, VKORC1 was found functionally, to be highly polymorphic with 53.7% of Saudi individuals harboring variants predicted to result in decreased activity and 31.3% having variants leading to increased metabolic activity. Furthermore, among the 8 pharmacogenes studied, we detected six rare variants with an aggregated frequency of 1.1%, that among several other ethnicities, were uniquely found in Saudi population. Similarly, within our cohort, the 8 pharmacogenes yielded forty-six novel variants predicted to be deleterious. Based upon our findings, 99.2% of individuals from the Saudi population carry at least one actionable pharmacogenetic variant.

Ecological divergence in a species provides a valuable opportunity to study the early stages of speciation. We focused on Metrosideros polymorpha, a unique example of the incipient radiation of woody species, to examine how an ecological divergence continues in the face of gene flow. We analyzed the whole genomes of 70 plants collected throughout the island of Hawaii, which is the youngest island with the highest altitude in the archipelago and encompasses a wide range of environments. The continuous M. polymorpha forest stands on the island of Hawaii were differentiated into three genetic clusters, each of which grows in a distinctive environment and includes substantial genetic and phenotypic diversity. The three genetic clusters showed signatures of selection in genomic regions encompassing genes relevant to environmental adaptations, including genes associated with light utilization, oxidative stress, and leaf senescence, which are likely associated with the ecological differentiation of the species. Our demographic modeling suggested that the glaberrima cluster in wet environments maintained a relatively large population size and two clusters split: polymorpha in the subalpine zone and incana in dry and hot conditions. This ecological divergence possibly began before the species colonized the island of Hawaii. Interestingly, the three clusters recovered genetic connectivity coincidentally with a recent population bottleneck, in line with the weak reproductive isolation observed in the species. This study highlights that the degree of genetic differentiation between ecologically-diverged populations can vary depending on the strength of natural selection in the very early phases of speciation., Author summary Knowledge about how genetic barriers are formed between populations in distinct environments is valuable to understand the processes of speciation and conserve biodiversity. Metrosideros polymorpha, an endemic woody species in the Hawaiian Islands, is a good system to study developing genetic barriers in a species, because it colonized the diverse environments and diversified the morphology for a relatively short period of time. We analyzed the genomes of 70 M. polymorpha plants from a broad range of environments on the island of Hawaii to infer the current and past genetic barriers among them. Currently, M. polymorpha plants growing in different environments have substantially different genomes, especially at the genomic regions with genes putatively controlling physiology to fit in distinct environment. However, in its history, they had hybridized with one another, possibly because plants formerly growing in different environments came into close contact due to the climate changes. It is suggested that genetic barriers can easily strengthen or weaken depending on environments splitting the ecology of a species before reproductive isolation becomes complete.

Genome-wide association studies rely on the statistical inference of untyped variants, called imputation, to increase the coverage of genotyping arrays. However, the results are often suboptimal in populations underrepresented in existing reference panels and array designs, since the selected single nucleotide polymorphisms (SNPs) may fail to capture population-specific haplotype structures, hence the full extent of common genetic variation. Here, we propose to sequence the full genomes of a small subset of an underrepresented study cohort to inform the selection of population-specific add-on tag SNPs and to generate an internal population-specific imputation reference panel, such that the remaining array-genotyped cohort could be more accurately imputed. Using a Tanzania-based cohort as a proof-of-concept, we demonstrate the validity of our approach by showing improvements in imputation accuracy after the addition of our designed add-on tags to the base H3Africa array., Author summary Genome-wide association studies, which study the association between genetic variants and various phenotypes, typically rely on genotyping arrays. Only a small proportion of genetic variants within the genome are typed on genotyping arrays. Untyped variants are statistically inferred through a process known as genotype imputation, where correlations between variants (haplotypes) observed in external reference panels are leveraged to infer untyped variants in the study population. However, for study populations that are underrepresented in existing reference panels, the quality of imputation is often sub-optimal. This is because typed variants incorporated on existing genotyping arrays can be unsuitable for the study population, and haplotype structures can be different between the reference and the study population. Here, we illustrate an approach to select a custom set of population-specific typed variants to improve genotype imputation in such underrepresented populations.

Insecticide resistance is a major threat to gains in malaria control, which have been stalling and potentially reversing since 2015. Studies into the causal mechanisms of insecticide resistance are painting an increasingly complicated picture, underlining the need to design and implement targeted studies on this phenotype. In this study, we compare three populations of the major malaria vector An. coluzzii: a susceptible and two resistant colonies with the same genetic background. The original colonised resistant population rapidly lost resistance over a 6-month period, a subset of this population was reselected with pyrethroids, and a third population of this colony that did not lose resistance was also available. The original resistant, susceptible and re-selected colonies were subject to RNAseq and whole genome sequencing, which identified a number of changes across the transcriptome and genome linked with resistance. Firstly, an increase in the expression of genes within the oxidative phosphorylation pathway were seen in both resistant populations compared to the susceptible control; this translated phenotypically through an increased respiratory rate, indicating that elevated metabolism is linked directly with resistance. Genome sequencing highlighted several blocks clearly associated with resistance, including the 2Rb inversion. Finally, changes in the microbiome profile were seen, indicating that the microbial composition may play a role in the resistance phenotype. Taken together, this study reveals a highly complicated phenotype in which multiple transcriptomic, genomic and microbiome changes combine to result in insecticide resistance., Author summary Insecticide resistance in major malaria vectors represents the single biggest threat to malaria control programs, which are heavily reliant upon insecticide-based interventions. Studying resistance using multi-omics approaches has proven difficult due to the use of susceptible comparator populations that have been colonised in a laboratory setting for decades, leading to substantial noise in the data due to differing genetic backgrounds. Here, we utilise a resistant Anopheles coluzzii population from Burkina Faso, a derived population that rapidly lost resistance over a 6-month period, and a population re-selected after loss of resistance to explore causative mechanisms of insecticide resistance. To determine the underlying cause of this phenotype, we use RNAseq, whole genome sequencing and lab-based validation to show changes in respiratory rate, wide-ranging genomic changes and alterations in the microbiome are linked to resistance in this population. These findings demonstrate the complexity of resistance and the challenges in utilising diagnostic markers for resistance in a field setting.

Ecological restoration can promote biodiversity conservation in anthropogenically fragmented habitats, but effectiveness of these management efforts need to be statistically validated to determine ’success.’ One such approach is to gauge the extent of recolonization as a measure of landscape permeability and, in turn, population connectivity. In this context, we estimated dispersal and population connectivity in prairie vole (Microtus ochrogaster; N = 231) and meadow vole (M. pennsylvanicus; N = 83) within five tall-grass prairie restoration sites embedded within the agricultural matrix of midwestern North America. We predicted that vole dispersal would be constrained by the extent of agricultural land surrounding restored habitat patches, spatially isolating vole populations and resulting in significant genetic structure. We first employed genetic assignment tests based on 15 microsatellite DNA loci to validate field-derived species-designations, then tested reclassified samples with multivariate and Bayesian clustering to assay for spatial and temporal genetic structure. Population connectivity was further evaluated by calculating pairwise FST, then potential demographic effects explored by computing migration rates, effective population size (Ne), and average relatedness (r). Genetic species assignments reclassified 25% of initial field identifications (N = 11 M. ochrogaster; N = 67 M. pennsylvanicus). In M. ochrogaster population connectivity was high across the study area, reflected in little to no spatial or temporal genetic structure. In M. pennsylvanicus genetic structure was detected, but relatedness estimates identified it as kin-clustering instead, underscoring social behavior among populations rather than spatial isolation as the cause. Estimates of Ne and r were stable across years, reflecting high dispersal and demographic resilience. Combined, these metrics suggest the agricultural matrix is highly permeable for voles and does not impede dispersal. High connectivity observed confirms that the restored landscape is productive and permeable for specific management targets such as voles and also demonstrates population genetic assays as a tool to statistically evaluate effectiveness of conservation initiatives.

Credible estimates suggest that a large number of the nearly 7000 languages in the world could go extinct this century, a prospect with profound cultural, socioeconomic, and political ramifications. Despite its importance, we still have little predictive theory for language dynamics and richness. Critical to the language extinction problem, however, is to understand the dynamics of the number of speakers of languages, the dynamics of language abundance distributions (LADs). Many regional LADs are very similar to the bell-shaped distributions of relative species abundance predicted by neutral theory in ecology. Using the tenets of neutral theory, here we show that LADs can be understood as an equilibrium or disequilibrium between stochastic rates of origination and extinction of languages. However, neutral theory does not fit some regional LADs, which can be explained if the number of speakers has grown systematically faster in some languages than others, due to cultural factors and other non-neutral processes. Only the LADs of Australia and the United States, deviate from a bell-shaped pattern. These deviations are due to the documented higher, non-equilibrium extinction rates of low-abundance languages in these countries.

Potato starch is an essential nutrient for humans and is widely used worldwide. Locating relevant genomic regions, mining stable genes and developing candidate gene markers can promote the breeding of new high-starch potato varieties. A total of 106 F1 individuals and their parents (YSP-4 × MIN-021) were used as test materials, from which 20 plants with high starch content and 20 with low starch content were selected to construct DNA pools for site-specific amplified fragment sequencing (SLAF-seq) and bulked segregation analysis (BSA). A genomic region related to the starch traits was first identified in the 0–5.62 Mb of chromosome 2 in tetraploid potato. In this section, a total of 41 non-synonymous genes, which were considered as candidate genes related to the starch trait, were annotated through a basic local alignment search tool (BLAST) search of multiple databases. Six candidate genes for starch (PGSC0003DMG400017793, PGSC0003DMG400035245, PGSC0003DMG400036713, PGSC0003DMG400040452, PGSC0003DMG400006636 and PGSC0003DMG400044547) were further explored. In addition, cleaved amplified polymorphic sequence (CAPS) markers were developed based on single nucleotide polymorphism (SNP) sites associated with the starch candidate genes. SNP-CAPS markers chr2-CAPS6 and chr2-CAPS21 were successfully developed and validated with the F2 population and 24 tetraploid potato varieties (lines). Functional analysis and cloning of the candidate genes associated with potato starch will be performed in further research, and the SNP-CAPS markers chr2-CAPS6 and chr2-CAPS21 can be further used in marker-assisted selection breeding of tetraploid potato varieties with high starch content.

The human sex ratio at birth (SRB), defined as the ratio between the number of newborn boys to the total number of newborns, is typically slightly greater than 1/2 (more boys than girls) and tends to vary across different geographical regions and time periods. In this large-scale study, we sought to validate previously-reported associations and test new hypotheses using statistical analysis of two very large datasets incorporating electronic medical records (EMRs). One of the datasets represents over half (∼ 150 million) of the US population for over 8 years (IBM Watson Health MarketScan insurance claims) while another covers the entire Swedish population (∼ 9 million) for over 30 years (the Swedish National Patient Register). After testing more than 100 hypotheses, we showed that neither dataset supported models in which the SRB changed seasonally or in response to variations in ambient temperature. However, increased levels of a diverse array of air and water pollutants, were associated with lower SRBs, including increased levels of industrial and agricultural activity, which served as proxies for water pollution. Moreover, some exogenous factors generally considered to be environmental toxins turned out to induce higher SRBs. Finally, we identified new factors with signals for either higher or lower SRBs. In all cases, the effect sizes were modest but highly statistically significant owing to the large sizes of the two datasets. We suggest that while it was unlikely that the associations have arisen from sex-specific selection mechanisms, they are still useful for the purpose of public health surveillance if they can be corroborated by empirical evidences., Author summary The human sex ratio at birth (SRB), usually slightly greater than 1/2, have been reported to vary in response to a wide array of exogenous factors. In the literature, many such factors have been posited to be associated with higher or lower SRBs, but the studies conducted so far have focused on no more than a few factors at a time and used far smaller datasets, thus prone to generating spurious correlations. We performed a series of statistical tests on 2 large, country-wide health datasets representing the United States and Sweden to investigate associations between putative exogenous factors and the SRB, and were able to validate a set of previously-reported associations while also discovering new signals. We propose to interpret these results simply as public health indicators awaiting further empirical confirmation rather than as implicated in (adaptive) sexual selection mechanisms.

Determining the drivers of plant rarity is a major challenge in ecology. Analysing spatial associations between different plant species can provide an exploratory avenue for understanding the ecological drivers of plant rarity. Here, we examined the different types of spatial associations between rare and common plants to determine if they influence the occurrence patterns of rare species. We completed vegetation surveys at 86 sites in woodland, forest, and heath communities in south-east Australia. We also examined two different rarity measures to quantify how categorisation criteria affected our results. Rare species were more likely to have positive associations with both rare and common species across all three vegetation communities. However, common species had positive or negative associations with rare and other common species, depending on the vegetation community in which they occurred. Rare species were positively associated with species diversity in forest communities. In woodland communities, rare species were associated negatively with species diversity but positively associated with species evenness. Rare species with high habitat specificity were more clustered spatially than expected by chance. Efforts to understand the drivers of plant rarity should use rarity definitions that consider habitat specificity. Our findings suggest that examining spatial associations between plants can help understand the drivers of plant rarity.

International audience; Red cell blood group systems are crucial for safe transfusion, transplantation, and pregnancy monitoring. In addition, blood groups have long been investigated to decipher the origin of human populations, migration, adaptation, and admixture. However, since the extensive use of DNA polymorphisms in Anthropology, blood groups have been relegated to their primary application, blood transfusion. The finer genomic mapping of some Neanderthal and Denisova individuals about modern humans has provided significant evidence on the evolutionary history of both archaic and modern humans. However, despite their medical and anthropological interest, little is known about blood groups in archaic populations. To better understand the origin, expansion and encounter with Homo sapiens, we reappraised the available high-quality sequences of three Neanderthals (Vindija 33.19, Chagyrskaya 8, Altai Neandertal) and one Denisovan (Denisova 3) for 11 genes of the 7 blood group systems that are routinely screened in transfusion: ABO including H/ Se, Rh (Rhesus), Kell, Duffy, Kidd, MNS, and Diego. We show that Neanderthals and Denisova were polymorphic for ABO and shared blood group alleles recurrent in modern Sub-Saharan populations. Furthermore, we found ABO-related alleles currently preventing viral gut infection and all Neanderthal shared RHD and RHCE alleles nowadays associated with a high risk of hemolytic disease of the fetus and newborn. Such a common blood group pattern across time and space is coherent with a Neanderthal population of low genetic diversity exposed to possible pregnancies with complications. Lastly, we connect the Neanderthal RHD allele to two present-day Aboriginal Australians and Papuan, suggesting that a segment of the archaic genome was introgressed in this gene in non-Eurasian populations before their expansion towards Oceania. While contributing to both the origin and late evolutionary history of Neanderthal and Denisova, our results further illustrate that blood group systems remain effective anthropological markers.

In many models of evolving populations, genetic drift has an outsized role relative to natural selection, or vice versa. While there are many scenarios in which one of these two assumptions is reasonable, intermediate balances between these forces are also biologically relevant. In this study, we consider some natural axioms for modeling intermediate selection intensities, and we explore how to quantify the long-term evolutionary dynamics of such a process. To illustrate the sensitivity of evolutionary dynamics to drift and selection, we show that there can be a “sweet spot” for the balance of these two forces, with sufficient noise for rare mutants to become established and sufficient selection to spread. This balance allows prosocial traits to evolve in evolutionary models that were previously thought to be unconducive to the emergence and spread of altruistic behaviors. Furthermore, the effects of selection intensity on long-run evolutionary outcomes in these settings, such as when there is global competition for reproduction, can be highly non-monotonic. Although intermediate selection intensities (neither weak nor strong) are notoriously difficult to study analytically, they are often biologically relevant; and the results we report suggest that they can elicit novel and rich dynamics in the evolution of prosocial behaviors., Author summary Theoretical models of populations have been useful for assessing when and how traits spread, in large part because they are simple. Rather than being used to reproduce empirical data, these idealized models involve relatively few parameters and are utilized to gain a qualitative understanding of what promotes or suppresses a trait. For prosocial traits, which entail a cost to self to help another, one thing that mathematical models often suggest is that competition to reproduce must be localized, meaning an individual must be fitter than just a small subset of the population in order to produce an offspring. We show here that this finding is not robust. Such traits can indeed proliferate when there is global competition for reproduction, which we demonstrate by increasing the degree to which payoffs from games affect birth rates. Since this kind of “stronger selection” has also been observed empirically, we discuss how it is incorporated into theoretical models more broadly.

Arthropod-borne viruses (arboviruses) require replication across a wide range of temperatures to perpetuate. While vertebrate hosts tend to maintain temperatures of approximately 37°C—40°C, arthropods are subject to ambient temperatures which can have a daily fluctuation of > 10°C. Temperatures impact vector competence, extrinsic incubation period, and mosquito survival unimodally, with optimal conditions occurring at some intermediate temperature. In addition, the mean and range of daily temperature fluctuations influence arbovirus perpetuation and vector competence. The impact of temperature on arbovirus genetic diversity during systemic mosquito infection, however, is poorly understood. Therefore, we determined how constant extrinsic incubation temperatures of 25°C, 28°C, 32°C, and 35°C control Zika virus (ZIKV) vector competence and population dynamics within Aedes aegypti and Aedes albopictus mosquitoes. We also examined fluctuating temperatures which better mimic field conditions in the tropics. We found that vector competence varied in a unimodal manner for constant temperatures peaking between 28°C and 32°C for both Aedes species. Transmission peaked at 10 days post-infection for Aedes aegypti and 14 days for Aedes albopictus. Conversely, fluctuating temperature decreased vector competence. Using RNA-seq to characterize ZIKV population structure, we identified that temperature alters the selective environment in unexpected ways. During mosquito infection, constant temperatures more often elicited positive selection whereas fluctuating temperatures led to strong purifying selection in both Aedes species. These findings demonstrate that temperature has multiple impacts on ZIKV biology, including major effects on the selective environment within mosquitoes., Author summary Arthropod-borne viruses (arboviruses) have emerged in recent decades due to complex factors that include increases in international travel and trade, the breakdown of public health infrastructure, land use changes, and many others. Climate change also has the potential to shift the geographical ranges of arthropod vectors, consequently increasing the global risk of arbovirus infection. Changing temperatures may alter the virus-host interaction, ultimately resulting in the emergence of new viruses and virus genotypes in new areas. Therefore, we sought to characterize how temperature (both constant and fluctuating) alters the ability of Aedes aegypti and Aedes albopictus to transmit Zika virus, and how it influences virus populations within mosquitoes. We found that intermediate temperatures maximize virus transmission compared to more extreme and fluctuating temperatures. Constant temperatures increased positive selection on virus genomes, while fluctuating temperatures strengthened purifying selection. Our studies provide evidence that in addition to altering vector competence, temperature significantly influences natural selection within mosquitoes.

Introduction Paracoccidioidomycosis (PCM) is caused by several species of the Paracoccidioides genus which can be differentiated by interspecific genetic variations, morphology and geographic distribution. Intraspecific variability correlation with clinical and epidemiological aspects of these species still remains unclear. This study aimed to sequence the loci GP43, exon 2 and ARF of 23 clinical isolates of Paracoccidioides spp. from patients in the Southeast Region of Brazil. Methodology and main findings GenBank was used to compare the present (23) with previous described sequences (151) that included ARF and GP43. It was identified a high polymorphism rate among the 23 isolates in comparison to the other 151. Among the isolates, 22 (95.66%) were S1/P. brasiliensis and 1 (4.34%) was identified as PS2/P. americana. A total of 45 haplotypes were found as follows: 19 from S1/P. brasiliensis (13 from the present study), 15 from P. lutzii, 6 from PS2/P. americana (1 from the present study), 3 from PS3/P. restrepiensis and 2 from PS4/P. venezuelensis. Moreover, exclusive haplotypes according to clinical origin and geographical area were found. S1/P. brasiliensis (HD = 0.655 and K = 4.613) and P. lutzii (HD = 0.649 and K = 2.906) presented the highest rate of polymorphism among all species, from which 12 isolates of the present study were clustered within S1b/P. brasiliensis. The GP43 locus showed a higher variability and was found to be the main reason for the species differentiation. Conclusions The results herein decribed show a high intraspecific genetic variability among S1/P. brasiliensis isolates and confirm the predominance of this species in the Southeast region of Brazil. The finding of exclusive haplotypes according to clinical origin and geographical area would suggest correlation between the molecular profile with the clinical form and geographic origin of patients with PCM., Author summary Paracoccidioidomycosis (PCM) is one of the most important systemic mycosis of Latin America. This disease can be caused by Paracoccidioides lutzii and four different phylogenetic species: S1/Paracoccidioides brasiliensis sensu stricto that harboring S1a and S1b, PS2/Paracoccidioides americana, PS3/Paracoccidioides restrepiensis and PS4/Paracoccidioides venezuelensis. Some of these species show differences in their main geographic region of predominance such as PS2/P. americana that can be found in Venezuela and Southern Brazil; PS3/P. restrepiensis and PS4/P. venezuelensis which are distributed in Colombia and Venezuela. However, and due to their wide geographical distribution, the species S1/P. brasiliensis and P. lutzii overlapping ecological niches and can be found in different regions of Brazil and other Latin American countries. Regarding eco-epidemiological aspects, the habitat is believed to be the soil due to the predominance of the disease among rural workers who become infected by inhaling infectious propagules during their farm activities. According to other authors, these species could have relation with the different PCM clinical presentation. This study aimed to describe the molecular epidemiology associated with clinical and epidemiological data of Paracoccidiodes spp. in the Minas Gerais State, located in the Southeast region, Brazil. Among the 23 isolates herein evaluated, 22 were S1/P. brasiliensis and 1 was identified as PS2/P. americana. A total of 45 haplotypes were found when these isolates were compared with other 151 deposited in the Genbank. The preliminar finding of exclusive haplotypes according to clinical origin and geographical area would suggest correlation between the molecular profile with the clinical form and geographic origin of patients with PCM. The GP43 locus showed a higher variability and was found to be the main promotor of species differentiation. The results herein described pointed out a high intraspecific genetic variability among S1/P. brasiliensis isolates and confirm the predominance of this species in the Southeast region of Brazil.

The growing number of next-generation sequencing (NGS) data presents a unique opportunity to study the combined impact of mitochondrial and nuclear-encoded genetic variation in complex disease. Mitochondrial DNA variants and in particular, heteroplasmic variants, are critical for determining human disease severity. While there are approaches for obtaining mitochondrial DNA variants from NGS data, these software do not account for the unique characteristics of mitochondrial genetics and can be inaccurate even for homoplasmic variants. We introduce MitoScape, a novel, big-data, software for extracting mitochondrial DNA sequences from NGS. MitoScape adopts a novel departure from other algorithms by using machine learning to model the unique characteristics of mitochondrial genetics. We also employ a novel approach of using rho-zero (mitochondrial DNA-depleted) data to model nuclear-encoded mitochondrial sequences. We showed that MitoScape produces accurate heteroplasmy estimates using gold-standard mitochondrial DNA data. We provide a comprehensive comparison of the most common tools for obtaining mtDNA variants from NGS and showed that MitoScape had superior performance to compared tools in every statistically category we compared, including false positives and false negatives. By applying MitoScape to common disease examples, we illustrate how MitoScape facilitates important heteroplasmy-disease association discoveries by expanding upon a reported association between hypertrophic cardiomyopathy and mitochondrial haplogroup T in men (adjusted p-value = 0.003). The improved accuracy of mitochondrial DNA variants produced by MitoScape will be instrumental in diagnosing disease in the context of personalized medicine and clinical diagnostics., Author summary Recent studies have highlighted the importance of mitochondrial DNA variation in both primary mitochondrial disease and complex, human pathology including COVID-19, and space-flight stress. The vast amount of existing, next-generation sequencing (NGS) data can be leveraged to interrogate both nuclear and mitochondrial DNA (mtDNA) sequence simultaneously, allowing for analysis of the interplay between mitochondrial and nuclear encoded genes in mitochondrial function. Identifying mtDNA sequence accurately is complicated by the presence of nuclear encoded mitochondrial sequences (NUMTs), which are homologous to mtDNA. Current software for analyzing mtDNA from NGS do not accurately model the unique characteristics of mitochondrial genetics. We introduce MitoScape, a novel, big-data, software which models mitochondrial genetics through machine learning to accurately identify mtDNA sequence from NGS data. MitoScape takes advantage of rho-zero cell data to model the characteristics of NUMTs. We show that MitoScape produces more accurate heteroplasmy estimates compared to published software. We provide an example of applying MitoScape in replicating an association between hypertrophic cardiomyopathy and mitochondrial haplogroup T in men. MitoScape is an important contribution to mitochondrial genomics allowing for accurate mtDNA variants, and the ability to tailor mtDNA analysis in different population and disease contexts, which is not available in other software.

Urbanisation alters landscapes, introduces wildlife to novel stressors, and fragments habitats into remnant ‘islands’. Within these islands, isolated wildlife populations can experience genetic drift and subsequently suffer from inbreeding depression and reduced adaptive potential. The Western tiger snake (Notechis scutatus occidentalis) is a predator of wetlands in the Swan Coastal Plain, a unique bioregion that has suffered substantial degradation through the development of the city of Perth, Western Australia. Within the urban matrix, tiger snakes now only persist in a handful of wetlands where they are known to bioaccumulate a suite of contaminants, and have recently been suggested as a relevant bioindicator of ecosystem health. Here, we used genome-wide single nucleotide polymorphism (SNP) data to explore the contemporary population genomics of seven tiger snake populations across the urban matrix. Specifically, we used population genomic structure and diversity, effective population sizes (Ne), and heterozygosity-fitness correlations to assess fitness of each population with respect to urbanisation. We found that population genomic structure was strongest across the northern and southern sides of a major river system, with the northern cluster of populations exhibiting lower heterozygosities than the southern cluster, likely due to a lack of historical gene flow. We also observed an increasing signal of inbreeding and genetic drift with increasing geographic isolation due to urbanisation. Effective population sizes (Ne) at most sites were small (< 100), with Ne appearing to reflect the area of available habitat rather than the degree of adjacent urbanisation. This suggests that ecosystem management and restoration may be the best method to buffer the further loss of genetic diversity in urban wetlands. If tiger snake populations continue to decline in urban areas, our results provide a baseline measure of genomic diversity, as well as highlighting which ‘islands’ of habitat are most in need of management and protection.

The sequence diversity of natural and laboratory populations of Brugia pahangi and Brugia malayi was assessed with Illumina resequencing followed by mapping in order to identify single nucleotide variants and insertions/deletions. In natural and laboratory Brugia populations, there is a lack of sequence diversity on chromosome X relative to the autosomes (πX/πA = 0.2), which is lower than the expected (πX/πA = 0.75). A reduction in diversity is also observed in other filarial nematodes with neo-X chromosome fusions in the genera Onchocerca and Wuchereria, but not those without neo-X chromosome fusions in the genera Loa and Dirofilaria. In the species with neo-X chromosome fusions, chromosome X is abnormally large, containing a third of the genetic material such that a sizable portion of the genome is lacking sequence diversity. Such profound differences in genetic diversity can be consequential, having been associated with drug resistance and adaptability, with the potential to affect filarial eradication., Author summary Almost a billion people receive >7.7 billion doses of treatment aimed at eliminating lymphatic filariasis, which is caused by three filarial nematodes: Wuchereria bancrofti, Brugia malayi, and Brugia timori. Drug resistance and adaptation are both associated with pathogen success as well as higher levels of genetic diversity. In an examination of genetic diversity in Brugia malayi and Brugia pahangi, we observed a lack of genetic diversity over a third of the genome that is found on chromosome X. These species have neo-X chromosomes where a chromosome X fused with an autosome. Using publicly-available published data, the other filarial nematodes of greatest human significance are also found to have a similar lack of genetic diversity on their neo-X chromosomes. The two filarial nematodes with publicly-available data that lack neo-X chromosomes did not have this lack of genetic diversity. This lack of sequence diversity in B. malayi, W. bancrofti, and O. volvulus could have profound effects on all traits encoded on chromosome X.

While often deleterious, hybridization can also be a key source of genetic variation and pre-adapted haplotypes, enabling rapid evolution and niche expansion. Here we evaluate these opposing selection forces on introgressed ancestry between maize (Zea mays ssp. mays) and its wild teosinte relative, mexicana (Zea mays ssp. mexicana). Introgression from ecologically diverse teosinte may have facilitated maize’s global range expansion, in particular to challenging high elevation regions (> 1500 m). We generated low-coverage genome sequencing data for 348 maize and mexicana individuals to evaluate patterns of introgression in 14 sympatric population pairs, spanning the elevational range of mexicana, a teosinte endemic to the mountains of Mexico. While recent hybrids are commonly observed in sympatric populations and mexicana demonstrates fine-scale local adaptation, we find that the majority of mexicana ancestry tracts introgressed into maize over 1000 generations ago. This mexicana ancestry seems to have maintained much of its diversity and likely came from a common ancestral source, rather than contemporary sympatric populations, resulting in relatively low FST between mexicana ancestry tracts sampled from geographically distant maize populations. Introgressed mexicana ancestry in maize is reduced in lower-recombination rate quintiles of the genome and around domestication genes, consistent with pervasive selection against introgression. However, we also find mexicana ancestry increases across the sampled elevational gradient and that high introgression peaks are most commonly shared among high-elevation maize populations, consistent with introgression from mexicana facilitating adaptation to the highland environment. In the other direction, we find patterns consistent with adaptive and clinal introgression of maize ancestry into sympatric mexicana at many loci across the genome, suggesting that maize also contributes to adaptation in mexicana, especially at the lower end of its elevational range. In sympatric maize, in addition to high introgression regions we find many genomic regions where selection for local adaptation maintains steep gradients in introgressed mexicana ancestry across elevation, including at least two inversions: the well-characterized 14 Mb Inv4m on chromosome 4 and a novel 3 Mb inversion Inv9f surrounding the macrohairless1 locus on chromosome 9. Most outlier loci with high mexicana introgression show no signals of sweeps or local sourcing from sympatric populations and so likely represent ancestral introgression sorted by selection, resulting in correlated but distinct outcomes of introgression in different contemporary maize populations., Author summary When species expand their ranges, new encounters with diverse wild relatives can introduce deleterious genetic variation, but may also accelerate the colonization of novel environments by providing ‘ready-made’ genetic adaptations. Maize today is a global staple, far exceeding the original ecological niche of its wild progenitor. We show that gene flow from highland-endemic wild mexicana facilitated maize’s range expansion from the valleys where it was domesticated to sites over 1500m in the mountains of Mexico. We find loci where mexicana ancestry has been repeatedly favored in highland maize populations. We also find loci (including a newly identified inversion) where mexicana ancestry increases steeply with elevation, providing evidence for adaptive trade-offs. We additionally demonstrate selection against mexicana ancestry, especially near domestication genes. We sampled mexicana growing alongside maize fields, yet find little evidence that introgression is recent or locally-sourced genomewide or at adaptive loci. Rather, the majority of mexicana ancestry was introduced into maize over 1000 generations ago, and subsequently diverged and was sorted by selection in individual populations. These results add to our understanding of the effects of introgression on range expansions and adaptation.

In a previous study, we developed a Multi-Locus VNTRs Analysis (MLVA) typing system, called MLVA-5, for the discrimination of Chlamydia trachomatis genovar E strain. The results suggested the clonal spread of a MLVA-5 type 21 strain among men who have sex with men (MSM). We applied the MLVA-5 typing method on 157 French anorectal genovar E specimens and 19 Swedish specimens collected between 2010 and 2015. A total of 29 MLVA-5 types was obtained, with three predominant types among French samples: 78 specimens belonged to MLVA-5 type 21, two other types, 11 and 13, included 9 and 14 specimens, respectively. In 15 cases, one unique MLVA-5 type was observed for a single patient, 7 of which were new types not previously described. The distribution of MLVA-5 types according to sexual orientation showed that the 7 anorectal specimens from heterosexual patients belonged to 6 genotypes, and the 12 anorectal specimens from bisexual patients comprised eight types. The 95 anorectal specimens from MSM were distributed into 22 types, but 55 (57.9%) of them belonged to MLVA-5 type 21. Among the Swedish specimens from MSM, eight were from MLVA-type 21 (4 urines and 4 anorectal specimens). The results support the hypothesis of the spread of clonal genovar E strain among MSM.

The present study investigated an integrated life course model, drawn from the life course theoretical perspective, to elucidate youth’s additive, cascading, and cumulative life course processes stemming from early socioeconomic adversity and education polygenic score (education PGS) as well as potential interactions between them (GxE), which contribute to subsequent young adult socioeconomic outcomes. Additionally, the independent, varying associations among social and genetic predictors, life-stage specific educational outcomes (educational achievement in adolescence and educational attainment, in later stages), and young adult economic outcomes were examined. The study used prospective, longitudinal data from the National Longitudinal Study of Adolescent and Adult Health (Add Health) with a sample of 5,728 youth of European ancestry. Early family socioeconomic adversity and individual education PGS were associated with life stage-specific educational outcomes through additive and cascading processes linked to young adults’ economic outcomes (personal earnings) through a cumulative process. A GxE moderation existed between individuals’ education PGS and early socioeconomic adversity at multiple life stages, explaining variation in adolescent educational outcomes. Both early socioeconomic adversity and education PGS were persistently associated with youth’s educational and economic outcomes throughout the early life course. In sum, the findings based on the integrated life course model showed how additive, cascading, and cumulative processes were related and conditioned one another, generating specific life course patterns and outcomes. The findings highlight the value of incorporating molecular genetic information into longitudinal developmental life course research and provide insight into malleable characteristics and appropriate timing for interventions addressing youth developmental characteristics.

Sri Lanka is an amphibian hotspot of global significance. Its anuran fauna is dominated by the shrub frogs of the genusPseudophilautus. Except for one small clade of four species in Peninsular India, these cool-wet adapted frogs, numbering some 59 extant species, are distributed mainly across the montane and lowland rain forests of the island. With species described primarily by morphological means, the diversification has never yet been subjected to a molecular species delimitation analysis, a procedure now routinely applied in taxonomy. Here we test the species boundaries ofPseudophilautusin the context of the phylogenetic species concept (PSC). We use all the putative species for which credible molecular data are available (nDNA–Rag-1; mt-DNA– 12S rRNA, 16S rRNA) to build a well resolved phylogeny, which is subjected to species delimitation analyses. The ABGD, bPTP, mPTP and bGMYC species delimitation methods applied to the 16S rRNA frog barcoding gene (for all species), 12S rRNA and Rag-1 nDNA groupedP.procaxandP.abundus;P.hallidayiandP.fergusonianus;P.reticulatusandP.pappilosus;P.pleurotaeniaandP.hoipolloi;P.hoffmaniandP.asankai;P.silvaticusandP.limbus;P.dilmahandP.hankeni;P.fulvusandP.silus.. Surprisingly, all analyses recovered 14 unidentified potential new species as well. The geophylogeny affirms a distribution across the island’s aseasonal ‘wet zone’ and its three principal hill ranges, suggestive of allopatric speciation playing a dominant role, especially between mountain masses. Among the species that are merged by the delimitation analyses, a pattern leading towards a model of parapatric speciation emerges–ongoing speciation in the presence of gene flow. This delimitation analysis reinforces the species hypotheses, paving the way to a reasonable understanding of Sri LankanPseudophilautus, enabling both deeper analyses and conservation efforts of this remarkable diversification.http://zoobank.org/urn:lsid:zoobank.org:pub:DA869B6B-870A-4ED3-BF5D-5AA3F69DDD27.

Background The Asian tiger mosquito, Aedes albopictus, has spread around the world. The migration was mainly mediated by maritime transportations. This species is known as an efficient vector for arboviruses, and it was responsible for the recent dengue outbreak in Tokyo, Japan. As the vector competence varies among geographical populations, and insecticide resistant populations have emerged, it is important to reveal their movements. The present study uses molecular techniques to search for a sign of introduction of an exotic population in three major international seaports on Kyushu Island. Methodology/principal findings Adults of Ae. albopictus were sampled around the international seaports of Fukuoka, Kitakyushu, and Nagasaki. Pairwise fixation indexes were estimated between the sampled populations based on 13 microsatellite markers. There was no clear genetic differentiation between distant and port populations in Kitakyushu and Nagasaki. However, the analysis found one distinct group near the container terminal in Fukuoka, which handles international freight containers mainly from adjacent countries. DNA samples were also obtained from Goto, Tsushima, Honshu, Ryukyu, Thailand, and the Philippines; and a cluster analysis and discriminant analysis revealed that the distinct group in Fukuoka did not belong to these groups. Combined with the results of phylogenetic analysis based on CO1, these results implied that this group originated from one Asian temperate region outside of Japan. Neutrality test and mismatch distribution analysis suggested that the establishment of this group was not recent. Conclusions/significance The present study found a sign of Ae. albopictus introduction from a temperate region of Asia through maritime freight container transportation. The genetically distinct group found in Fukuoka likely originated from a temperate region outside of Japan. Maritime container transportation may introduce to Japan mosquitoes with greater vector competence/insecticide resistance. This is the first study to describe the spatial population structure of Ae. albopictus in Japan using molecular techniques., Author summary Aedes albopictus is an invasive species and an efficient disease vector. The bioecological traits of this species and human-mediated transportations have fueled its worldwide spread. Because the levels of vector competence and insecticide resistance vary among geographical strains, the worldwide migration of this species is a concern for public health and vector control. While numerous studies have been done in non-native areas, within its native areas in Asia movements have not been explored. This study used molecular techniques to search for signs of introduction of an exotic population through three major international seaports on Kyushu Island, Japan. The present study found a genetically distinct group of Ae. albopictus near the container terminal in Fukuoka. The study suggests that its origin was one temperate region of East Asia outside of Japan, and the establishment of this group was not recent. As vector competence varies among different populations and the knock down resistance gene has been reported from some populations outside Japan, the risk of introducing mosquitoes with greater vector competence/insecticide resistance needs to be considered. This is the first study to describe the spatial population structure of Ae. albopictus in Japan using molecular techniques.

Background Pediculus humanus capitis or head louse is an obligate ectoparasite and its infestation remains a major public health issue worldwide. Molecular analysis divides head lice into six clades and intra-clade genetic differences have been identified. Several hypotheses have been formulated to elucidate the discrepancies of the variety of head lice among different regions of the world. It is currently concluded that head lice distribution might be associated with human migration history. This study aims to investigate genetic data of human head lice in Thailand. We believe that the analysis could help establish the correlation between local and global head lice populations. Method We investigated mitochondrial cytochrome b (cytb) gene of the collected 214 head lice to evaluate genetic diversity from 15 provinces among 6 regions of Thailand. The head lice genes were added to the global pool for the phylogenetic tree, Bayesian tree, Skyline plot, and median joining network construction. The biodiversity, neutrality tests, and population genetic differentiation among the 6 Thailand geographic regions were analyzed by DNAsp version 6. Results The phylogenetic tree analysis of 214 collected head lice are of clade A and clade C accounting for roughly 65% and 35% respectively. The Bayesian tree revealed a correlation of clade diversification and ancient human dispersal timeline. In Thailand, clade A is widespread in the country. Clade C is confined to only the Central, Southern, and Northeastern regions. We identified 50 novel haplotypes. Statistical analysis showed congruent results between genetic differentiation and population migration especially with South Asia. Conclusions Pediculosis remains problematic among children in the rural areas in Thailand. Cytb gene analysis of human head lice illustrated clade distribution and intra-clade diversity of different areas. Our study reported novel haplotypes of head lice in Thailand. Moreover, the statistic calculation provided a better understanding of their relationship with human, as an obligate human parasite and might help provide a better insight into the history of human population migration. Determination of the correlation between phylogenetic data and pediculicide resistance gene as well as residing bacteria are of interest for future studies.

Beside diagnostic uncertainties due to the lack of a perfect gold standard test for Helicobacter pylori infection, the diagnosis and the prevalence estimation for this infection encounter particular challenges in Africa including limited diagnostic tools and specific genetic background. We developed and evaluated the accuracy of an enzyme-linked immunosorbent assay (ELISA) system tailored for H. pylori genetics in Africa (HpAfr-ELISA). Strains belonging to main genetic populations infecting Africans were exploited as sources for whole-cell antigens to establish in-house the ELISA system. A phase II unmatched case-control study explored the diagnostic accuracy of the HpAfr-ELISA using a training set of samples collected from dyspeptic patients from Kinshasa, the Democratic Republic of Congo (DRC) who had been tested with invasive standard tests (i.e., histology, culture, and rapid urease test) in 2017. Then the assay was cross-validated through a community-based survey assessing the prevalence of H. pylori and associated factors in 425 adults from Mbujimayi, DRC in 2018. Bayesian inferences were used to deal with statistical uncertainties of estimates (true prevalence, sensitivity, and specificity) in the study population. At its optimal cut-off-value 20.2 U/mL, the assay achieved an estimated sensitivity of 97.6% (95% credible interval [95%CrI]: 89.2; 99.9%) and specificity of 90.5% (95%CrI: 78.6; 98.5). Consistent outcomes obtained at repeated tests attested the robustness of the assay (negative and positive agreements always > 70%). The true prevalence of H. pylori was estimated 53.8% [95%CrI: 42.8; 62.7%]. Increasing age (adjusted odds ratio [aOR] > 1.0 [95% confidence interval (CI): > 1.0; 1.1]; p, Author summary Enzyme-linked immunosorbent assay (ELISA) systems are useful tools for mass screening of Helicobacter pylori infection but their use encounters important challenges in Africa. This is mainly due to the specific genetic background of African H. pylori that may jeopardize the accuracy of currently available ELISA kits. In this study, we developed a new ELISA system, i.e. HpAfr-ELISA, based on pooled antigens of H. pylori that represent main genetic populations colonizing Africa. This new assay could be validated analytically using training samples collected in H. pylori positive and negative patients from the Democratic Republic of Congo (DRC). Then, the tool was successfully applied to a real-world community-based mass survey aiming at assessing the epidemiology of H. pylori in a rural area of the DRC. The characteristics of the HpAfr-ELISA assay indicated good robustness and high performances for detection of H. pylori. Statistical modeling enabled estimating the true latent prevalence of H. pylori infection and identifying factors predicting the exposition to the infection in the study population. This outcome will be useful for drawing efficient health policies and optimally allocating available resources to fight the H. pylori infection and related complications (e.g., gastric cancer) in the study area and globally in Africa.

Aim The aim of the study is to investigate the trends in adult height between two consecutive surveys of NHFS and explore differences across variables such as gender, wealth, social groups etc. Methods We used the NFHS-II (1998–99), NFHS–III (2005–2006) and NFHS-IV (2015–16) (all three for women and last two for men) data to examine the trends in average height. Comparison was done between the two age strata of 15–25 and 26–50 years, across both male and female, to assess the trends. Results Between NFHS-III and NFHS-IV, the average height of women in the age group of 15–25 showed a decline by 0.12 cm [95% CI, -0.24 to 0.00, p-0.051] while in the 26–50 years age strata it demonstrated significant improvement in the mean height by 0.13 cm [95% CI, 0.02 to 0.023, p-0.015]. However, Between NFHS III and IV, the average height of women in the poorest wealth index category registered a significant decline [-0.57cm, 95% CI, -076 to -0.37, p-0.000]. Between NFHS III and IV, the average height of Scheduled Tribe (ST) women in the age group of 15–25 years also exhibited a significant decline by 0.42 cm, [95% CI, -0.73 to -0.12, p-0.007]. Among men, between the two surveys, both the age groups of 15–25 years and 26–50 years showed significant decline in average height: 1.10 cm [95% CI, -1.31 to -.099 cm, p-0.00] and 0.86 cm [95% CI, -1.03 to -0.69, p-0.000], respectively. Conclusion In the context of an overall increase in average heights worldwide the decline in average height of adults in India is alarming and demands an urgent enquiry. The argument for different standards of height for Indian population as different genetic group needs further scrutiny. However, the trends from India clearly underline the need to examine the non-genetic factors also to understand the interplay of genetic, nutritional and other social and environmental determinants on height.

Madagascar is a large island to the south-east of Africa and in many ways continental in size and ecological complexity. Here we aim to define how skull morphology of an endemic and monophyletic clade of rodents (sub-family Nesomyinae), that show considerable morphological variation, have evolved and how their disparity is characterized in context of the geographical and ecological complexity of the island. We performed a two-dimensional geometric morphometric analysis on 370 dorsal and 399 ventral skull images of 19 species (comprising all nine extant endemic genera) and tested the influence of three ecological parameters (climate, locomotor habitat and nychthemeral cycle) in a phylogenetic context on size and shape. The results indicate that skull shape appears to importantly reflect phylogeny, whereas skull size does not carry a significant phylogenetic signal. Skull shape is significantly influenced by climate while, skull size is not impacted by any of the ecological factors tested, which is controversial to expectations in an insular context. In conclusion, Nesomyinae must have evolved under unusual types of local constraints, preventing this radiation from demonstrating strong ecological release.

The calcium ion channel ORAI1 has emerged as a promising therapeutic target for the Coronavirus Disease 19 (COVID-19)-associated pneumonia, and a pharmacological inhibitor of ORAI1 has now reached clinical trials for severe COVID-19 pneumonia. Whether ORAI1 itself is associated with an increased risk for severe COVID-19 presentation is still unknown. Here, we employed genetic association analysis to investigate the potential association of host genetic polymorphisms of ORAI1 with the risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and its associated COVID-19 fatality in UK Biobank participants from white British background. The analysis showed no significant association between ORAI1 variants and COVID-19 positivity or fatality, despite the well-established roles of ORAI1 in immune response and inflammation and the success of ORAI1 inhibition in clinical trials. Our results suggest that the host genetic polymorphisms of ORAI1 are unlikely to be implicated in the broad variability in symptoms severity among afflicted patients.

The olfactory system combines input from multiple receptor types to represent odor information, but there are few explicit examples relating olfactory receptor (OR) activity patterns to odor perception. To uncover these relationships, we performed genome-wide scans on odor-perception phenotypes for ten odors in 1000 Han Chinese and validated results for six of these odors in an ethnically diverse population (n = 364). In both populations, consistent with previous studies, we replicated three previously reported associations (β-ionone/OR5A1, androstenone/OR7D4, cis-3-hexen-1-ol/OR2J3 LD-band), but not for odors containing aldehydes, suggesting that olfactory phenotype/genotype studies are robust across populations. Two novel associations between an OR and odor perception contribute to our understanding of olfactory coding. First, we found a SNP in OR51B2 that associated with trans-3-methyl-2-hexenoic acid, a key component of human underarm odor. Second, we found two linked SNPs associated with the musk Galaxolide in a novel musk receptor, OR4D6, which is also the first human OR shown to drive specific anosmia to a musk compound. We noticed that SNPs detected for odor intensity were enriched with amino acid substitutions, implying functional changes of odor receptors. Furthermore, we also found that the derived alleles of the SNPs tend to be associated with reduced odor intensity, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time. This study provides information about coding for human body odor, and gives us insight into broader mechanisms of olfactory coding, such as how differential OR activation can converge on a similar percept., Author summary Although genetic diversity in the olfactory receptor repertoire contributes to variation in odor perception, we have few explicit predictions relating variation in a specific OR to perception. Here, we performed genome-wide scans on odor-perception phenotypes for ten odors in 1000 Han Chinese and validated results for six of these odors in an ethnically diverse population (n = 364). We identified novel receptors for musk and human body odor that have implications for how structurally different molecules can have similar odors. Summarizing all the published genetic variation that associates with odor perception, we found that individuals with ancestral versions of the receptors tend to rate the corresponding odor as more intense, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time. This study of olfactory genetic and perceptual variation will improve our understanding of how the olfactory system encodes odor properties.

Bovine tuberculosis (bTB) caused by Mycobacterium (M.) bovis and M. caprae is a transmissible disease of livestock, notifiable to the World Organization for Animal Health (OIE). BTB particularly affects cattle and small ruminants and can be transmitted to humans thereby posing a significant threat to veterinary and public health worldwide. M. bovis is the principal cause of bTB in Algeria. In order to better understand the route of spreading and elaborate an eradication program, isolation and characterization of mycobacteria from Algerian cattle was performed. Sixty strains belonging to the M. tuberculosis complex were analyzed by spoligotyping, thereof 42 by 19-locus-MIRU-VNTR-typing. Spoligotyping revealed 16 distinguishable patterns (Hunter-Gaston discriminatory index [HGDI] of 0.8294), with types SB0120 (n = 20) and SB0121 (n = 13) being the most frequent patterns, representing 55% of the strains. Analyses based on 19-locus-MIRU-VNTR yielded 32 different profiles, five clusters and one orphan pattern, showing higher discriminatory power (HGDI = 0.9779) than spoligotyping. Seven VNTR-loci [VNTR 577 (alias ETR C), 2163b (QU11b), 2165 (ETR A), 2461 (ETR B), 3007 (MIRU 27), 2163a (QUB11a) and 3232 (QUB 3232)] were the most discriminative loci (HGDI ˃ 0.50). In conclusion, 19-locus-MIRU-VNTR yielded more information than spoligotyping concerning molecular differentiation of strains and better supports the elucidation of transmission routes of M. bovis between Algerian cattle herds.

Short tandem repeats (STRs) are highly informative genetic markers that have been used extensively in population genetics analysis. They are an important source of genetic diversity and can also have functional impact. Despite the availability of bioinformatic methods that permit large-scale genome-wide genotyping of STRs from whole genome sequencing data, they have not previously been applied to sequencing data from large collections of malaria parasite field samples. Here, we have genotyped STRs using HipSTR in more than 3,000 Plasmodium falciparum and 174 Plasmodium vivax published whole-genome sequence data from samples collected across the globe. High levels of noise and variability in the resultant callset necessitated the development of a novel method for quality control of STR genotype calls. A set of high-quality STR loci (6,768 from P. falciparum and 3,496 from P. vivax) were used to study Plasmodium genetic diversity, population structures and genomic signatures of selection and these were compared to genome-wide single nucleotide polymorphism (SNP) genotyping data. In addition, the genome-wide information about genetic variation and other characteristics of STRs in P. falciparum and P. vivax have been available in an interactive web-based R Shiny application PlasmoSTR (https://github.com/bahlolab/PlasmoSTR)., Author summary Malaria is a severe disease caused by a genus of parasites called Plasmodium and is transmitted to humans through infected Anopheles mosquitoes. P. falciparum and P. vivax are the predominant species responsible for more than 95% of all human malaria infections which continue to pose a significant challenge to human health. Antimalarial drug resistance is a serious threat hindering the elimination of malaria. As such, it is important to understand the role of genomic variation in the development of antimalarial drug resistance. STRs are an important source of genomic variation that, from a population genetics perspective, have several advantages over SNPs, including being highly polymorphic, having a higher mutation rate, and having been widely used to study population structure and genetic diversity. However, STRs are not routinely genotyped with bioinformatic tools across the whole genome with short read sequencing data because they are difficult to identify and genotype accurately, as they vary in size and may align poorly to the reference genome, therefore requiring rigorous quality control (QC). In this study, we genotype STRs using HipSTR in more than 3,000 P. falciparum and 174 P. vivax whole-genome sequence samples collected world-wide. We develop a multivariable logistic regression model for the measurement and prediction of the quality of STRs. In addition, we use a set of genome-wide high-quality STRs to study parasite population genetics and compare them to genome-wide SNP genotyping data, revealing both high consistency with SNP based signals, as well as identifying some signals unique to the STR marker data. These results demonstrate that the identification of highly informative STR markers from large numbers of population samples is a powerful approach to study the genetic diversity, population structures and genomic signatures of selection in P. falciparum and P. vivax. Furthermore, we built an interactive web-based R Shiny application PlasmoSTR (https://github.com/bahlolab/PlasmoSTR) that includes genome-wide information about genetic variation and other characteristics of the high quality STRs identified in P. falciparum and P. vivax, allowing researchers to explore and visualize the specific STRs.

To study viral evolutionary processes within patients, mathematical models have been instrumental. Yet, the need for stochastic simulations of minority mutant dynamics can pose computational challenges, especially in heterogeneous systems where very large and very small sub-populations coexist. Here, we describe a hybrid stochastic-deterministic algorithm to simulate mutant evolution in large viral populations, such as acute HIV-1 infection, and further include the multiple infection of cells. We demonstrate that the hybrid method can approximate the fully stochastic dynamics with sufficient accuracy at a fraction of the computational time, and quantify evolutionary end points that cannot be expressed by deterministic models, such as the mutant distribution or the probability of mutant existence at a given infected cell population size. We apply this method to study the role of multiple infection and intracellular interactions among different virus strains (such as complementation and interference) for mutant evolution. Multiple infection is predicted to increase the number of mutants at a given infected cell population size, due to a larger number of infection events. We further find that viral complementation can significantly enhance the spread of disadvantageous mutants, but only in select circumstances: it requires the occurrence of direct cell-to-cell transmission through virological synapses, as well as a substantial fitness disadvantage of the mutant, most likely corresponding to defective virus particles. This, however, likely has strong biological consequences because defective viruses can carry genetic diversity that can be incorporated into functional virus genomes via recombination. Through this mechanism, synaptic transmission in HIV might promote virus evolvability., Author summary The evolution of human immunodeficiency virus within patients is an important part of the disease process. In particular, the presence of mutants that are resistant against anti-viral drugs can result in challenges to the long-term control of the infection. To study disease progression, computer simulations have been useful. However, in some cases these simulations can be difficult because of the complexity of the model. Here, we use a computational complexity reducing algorithm to simulate mutant dynamics in large populations, which can approximate the full model at a fraction of the time. The use of this algorithm allows us to study different transmission methods, viral processes that occur between virus strains within individual cells, and important quantities such as the mutant distribution or the probability of mutant existence at a given infected cell population size. We find that the direct synaptic cell-to-cell transmission of the virus through virological synapses can have strong biological consequences because it can promote potentially defective viruses that carry genetic diversity which can be incorporated into functional virus genomes during infection. Through this process, synaptic transmission in human immunodeficiency virus might promote virus evolvability.

Background HIV outbreaks in the Former Soviet Union (FSU) countries were characterized by repeated transmission of the HIV variant AFSU, which is now classified as a distinct subtype A sub-subtype called A6. The current study used phylogenetic/phylodynamic and signature mutation analyses to determine likely evolutionary relationship between subtype A6 and other subtype A sub-subtypes. Methods For this study, an initial Maximum Likelihood phylogenetic analysis was performed using a total of 553 full-length, publicly available, reverse transcriptase sequences, from A1, A2, A3, A4, A5, and A6 sub-subtypes of subtype A. For phylogenetic clustering and signature mutation analysis, a total of 5961 and 3959 pol and env sequences, respectively, were used. Results Phylogenetic and signature mutation analysis showed that HIV-1 sub-subtype A6 likely originated from sub-subtype A1 of African origin. A6 and A1 pol and env genes shared several signature mutations that indicate genetic similarity between the two subtypes. For A6, tMRCA dated to 1975, 15 years later than that of A1. Conclusion The current study provides insights into the evolution and diversification of A6 in the backdrop of FSU countries and indicates that A6 in FSU countries evolved from A1 of African origin and is getting bridged outside the FSU region.

A recent research study on prevalence of tick-borne pathogens in Burundi reported high prevalence and endemicity of Theileria parva, Anaplasma marginale and Babesia bigemina infections in cattle. Detailed information about tick species infesting animals, their distribution and genetic diversity in Burundi is outdated and limited. This study therefore assessed the prevalence and genetic diversity of tick species infesting cattle across agroecological zones (AEZs) in Burundi. A cross-sectional study on the occurrence of tick species was conducted in 24 districts of Burundi between October and December 2017. Differential identification and characterization of ticks collected was conducted using tick morphological keys and molecular tools (cox1 and 12S rRNA gene). Chi-square test was used to test for association between agroecological zones and the prevalence of tick species. Phylogenetic relationships were inferred using bayesian and maximum likelihood algorithms. A total of 483 ticks were collected from the five AEZs sampled. Six tick species comprising of Rhipicephalus appendiculatus, R. sanguineus, R. evertsi evertsi, R. microplus, R. decoloratus and Amblyomma variegatum were observed. Rhipicephalus appendiculatus were the most prevalent ticks (~45%). A total of 138 specimens (28%) were found to be Rhipicephalus microplus, suggesting an emerging threat for cattle farmers. Twelve R. appendiculatus cox1 haplotypes were obtained from 106 specimens that were sequenced. Two cox1 haplotypes of R. microplus which clustered into previously reported Clade A were observed. Rhipicephalus sanguineus and R. evertsi evertsi ticks, the vectors of numerous zoonotic pathogens, were collected from cattle, which constitute a high risk for public health. These findings reveal an overlapping distribution of tick vectors in Burundi. The design of ticks and tick-borne diseases control strategies should consider the distribution of different vectors across the AEZs particularly the presence of the highly invasive R. microplus tick in Burundi and the potential risk of introducing the pathogenic Babesia bovis.

Purpose Immune responses for cancer cells can be altered according to genetic variation of human leukocyte antigen (HLA). Association of HLA polymorphism with risk of various cancer types is well known. However, the association between HLA and glioblastoma (GBM) remains uncertain. We sought to evaluate the association of HLA polymorphism with risk of GBM development in Koreans. Materials and methods A case-control study was performed to identify the odds ratios (OR) of HLA class I and II genes for GBM. The control group consisted of 142 healthy Korean volunteers, and the GBM group was 80 patients with newly diagnosed GBM at our institution. HLA class I (-A, -B, and–C) and class II (-DR, -DQ, and–DP) genotyping was performed by high-resolution polymerase chain reaction (PCR)-sequence-based typing (PCR-SBT) methods. Results There were significantly decreased frequencies of HLA-A*26:02 (OR 0.22 CI 0.05–0.98), HLA-C*08:01 (OR 0.29 CI 0.10–0.87), and HLA-DRB1*08:03 (OR 0.32 CI 0.11–0.98), while there was significantly increased frequency of HLA-C*04:01 (OR 2.29 CI 1.05–4.97). In analysis of haplotypes, the frequency of DRB1*14:05-DQB1*05:03 was significantly decreased (OR 0.22 CI 0.05–0.98). Conclusion This study suggests that genetic variations of HLA may affect GBM development in Koreans. Further investigations with larger sample sizes are needed to delineate any potential role of the HLA polymorphisms in the pathogenesis of GBM development.

The first confirmed case of COVID-19 in Quebec, Canada, occurred at Verdun Hospital on February 25, 2020. A month later, a localized outbreak was observed at this hospital. We performed tiled amplicon whole genome nanopore sequencing on nasopharyngeal swabs from all SARS-CoV-2 positive samples from 31 March to 17 April 2020 in 2 local hospitals to assess viral diversity (unknown at the time in Quebec) and potential associations with clinical outcomes. We report 264 viral genomes from 242 individuals–both staff and patients–with associated clinical features and outcomes, as well as longitudinal samples and technical replicates. Viral lineage assessment identified multiple subclades in both hospitals, with a predominant subclade in the Verdun outbreak, indicative of hospital-acquired transmission. Dimensionality reduction identified two subclades with mutations of clinical interest, namely in the Spike protein, that evaded supervised lineage assignment methods–including Pangolin and NextClade supervised lineage assignment tools. We also report that certain symptoms (headache, myalgia and sore throat) are significantly associated with favorable patient outcomes. Our findings demonstrate the strength of unsupervised, data-driven analyses whilst suggesting that caution should be used when employing supervised genomic workflows, particularly during the early stages of a pandemic.

Realistic models of biological processes typically involve interacting components on multiple scales, driven by changing environment and inherent stochasticity. Such models are often analytically and numerically intractable. We revisit a dynamic maximum entropy method that combines a static maximum entropy with a quasi-stationary approximation. This allows us to reduce stochastic non-equilibrium dynamics expressed by the Fokker-Planck equation to a simpler low-dimensional deterministic dynamics, without the need to track microscopic details. Although the method has been previously applied to a few (rather complicated) applications in population genetics, our main goal here is to explain and to better understand how the method works. We demonstrate the usefulness of the method for two widely studied stochastic problems, highlighting its accuracy in capturing important macroscopic quantities even in rapidly changing non-stationary conditions. For the Ornstein-Uhlenbeck process, the method recovers the exact dynamics whilst for a stochastic island model with migration from other habitats, the approximation retains high macroscopic accuracy under a wide range of scenarios in a dynamic environment., Author summary Complex processes in biology and physics have much in common. Collective motion of animals can be well described by models of interacting particles and emergent collective behavior can often be characterized as phase transitions of such a model. When the system is settled to a steady state, statistical physics connects random fluctuations of the process with key macroscopic quantities, using the maximum entropy method. It is thus not surprising that this method is in turn useful in understanding biological systems. However, realistic problems such as structured population dynamics, studied in our work, are set in dynamic environments, caused for instance by fluctuations in food supply. Therefore, we use the dynamical maximum entropy approximation, which allows us to reduce the full problem to simpler dynamics, without the need to track microscopic details. We focus on two processes (one in physics, one in biology) in our study: the motion of a charged particle and the dynamics of structured populations, both in a changing environment. We show that the method is extremely accurate even when the environmental changes are very fast, thus providing a powerful tool to study both biological and physical processes in changing environments.

Genome copy number variation occurs during each mitotic and meiotic cycle and it is crucial for organisms to maintain their natural ploidy. Defects in ploidy transitions can lead to chromosome instability, which is a hallmark of cancer. Ploidy in the haploid human fungal pathogen Cryptococcus neoformans is exquisitely orchestrated and ranges from haploid to polyploid during sexual development and under various environmental and host conditions. However, the mechanisms controlling these ploidy transitions are largely unknown. During C. deneoformans (formerly C. neoformans var. neoformans, serotype D) unisexual reproduction, ploidy increases prior to the onset of meiosis, can be independent from cell-cell fusion and nuclear fusion, and likely occurs through an endoreplication pathway. To elucidate the molecular mechanisms underlying this ploidy transition, we identified twenty cell cycle-regulating genes encoding cyclins, cyclin-dependent kinases (CDK), and CDK regulators. We characterized four cyclin genes and two CDK regulator genes that were differentially expressed during unisexual reproduction and contributed to diploidization. To detect ploidy transition events, we generated a ploidy reporter, called NURAT, which can detect copy number increases via double selection for nourseothricin-resistant, uracil-prototrophic cells. Utilizing this ploidy reporter, we showed that ploidy transition from haploid to diploid can be detected during the early phases of unisexual reproduction. Interestingly, selection for the NURAT reporter revealed several instances of segmental aneuploidy of multiple chromosomes, which conferred azole resistance in some isolates. These findings provide further evidence of ploidy plasticity in fungi with significant biological and public health implications., Author summary Ploidy is an intrinsic fundamental feature of all eukaryotic organisms, and ploidy variation and maintenance are critical to the organism survival and evolution. Fungi exhibit exquisite plasticity in ploidy variation in adaptation to various environmental stresses. For example, the haploid opportunistic human fungal pathogen C. deneoformans can generate diploid blastospores during unisexual reproduction and also forms polyploid titan cells during host infection; however, the mechanisms underlying these ploidy transitions are largely unknown. In this study, we elucidated the genetic regulatory circuitry governing ploidy duplication during C. deneoformans unisexual reproduction through the identification and characterization of cell cycle regulators that are differentially expressed during unisexual reproduction. We showed that four cyclin and two cyclin-dependent kinase regulator genes function in concert to orchestrate ploidy transition during unisexual reproduction. To trace and track ploidy transition events, we also generated a ploidy reporter and revealed the formation of segmental aneuploidy in addition to diploidization, illustrating the diverse mechanisms of genome plasticity in C. deneoformans.

Rhinoviruses (RV) are a major cause of Severe Acute Respiratory Infection (SARI) in children, with high genotypic diversity in different regions. However, RV type diversity remains unknown in several regions of the world. In this study, the genetic variability of the frequently circulating RV types in Northern Tunisia was investigated, using phylogenetic and phylogeographic analyses with a specific focus on the most frequent RV types: RV-A101 and RV-C45. This study concerned 13 RV types frequently circulating in Northern Tunisia. They were obtained from respiratory samples collected in 271 pediatric SARI cases, between September 2015 and November 2017. A total of 37 RV VP4-VP2 sequences, selected among a total of 49 generated sequences, was compared to 359 sequences from different regions of the world. Evolutionary analysis of RV-A101 and RV-C45 showed high genetic relationship between different Tunisian strains and Malaysian strains. RV-A101 and C45 progenitor viruses’ dates were estimated in 1981 and 1995, respectively. Since the early 2000s, the two types had a wide spread throughout the world. Phylogenetic analyses of other frequently circulating strains showed significant homology of Tunisian strains from the same epidemic period, in contrast with earlier strains. The genetic relatedness of RV-A101 and RV-C45 might result from an introduction of viruses from different clades followed by local dissemination rather than a local persistence of an endemic clades along seasons. International traffic may play a key role in the spread of RV-A101, RV-C45, and other RVs.