Genetic Isolation Research Articles

Genetic diversity and gene flow of the soil arthropod (Scolopendra mutilans) in urban landscapes: The roles of rivers, mountains and fragmentation

Abstract Soil invertebrates are a major element of soil biodiversity, which play critical roles in soil ecosystems. However, the impacts of urban landscapes on the genetic diversity and gene flows of soil arthropods remain unclear. Here, we studied the genetic diversity and gene flow of Scolopendra mutilans in an urban area using mitochondrial Cytb genes and eight novel microsatellite loci. A total of 22 haplotypes and 24 variation sites were identified based on 556 bp Cytb sequences from 84 individuals of five populations in Nanjing, Jiangsu Province, China. There were 5.63–8.00 alleles in the average of eight microsatellites found in the S. mutilans arthropod populations, which showed high genetic diversity in urban landscapes. There was no correlation between the natural habitat size and genetic diversity of S. mutilans. The global Fst value based on microsatellites was 0.115, which suggested a medium genetic differentiation and population isolation. The genetic structure of S. mutilans might be affected by urbanisation, as urban patches might hinder gene flow between populations. Ecological corridors preserved in cities might serve as pathways for population migration, which increases gene flow. The gene flows of S. mutilans might not be hindered by natural barriers within cities, as there were strong relationships between populations separated by rivers. These results may contribute to the conservation of S. mutilans diversity and elucidate its adaptation to urbanisation.

Carrot populations in France and Spain host a complex virome rich in previously uncharacterized viruses.

High-throughput sequencing (HTS) has proven a powerful tool to uncover the virome of cultivated and wild plants and offers the opportunity to study virus movements across the agroecological interface. The carrot model consisting of cultivated (Daucus carota ssp. sativus) and wild carrot (Daucus carota ssp. carota) populations, is particularly interesting with respect to comparisons of virus communities due to the low genetic barrier to virus flow since both population types belong to the same plant species. Using a highly purified double-stranded RNA-based HTS approach, we analyzed on a large scale the virome of 45 carrot populations including cultivated, wild and off-type carrots (carrots growing within the field and likely representing hybrids between cultivated and wild carrots) in France and six additional carrot populations from central Spain. Globally, we identified a very rich virome comprising 45 viruses of which 25 are novel or tentatively novel. Most of the identified novel viruses showed preferential associations with wild carrots, either occurring exclusively in wild populations or infecting only a small proportion of cultivated populations, indicating the role of wild carrots as reservoir of viral diversity. The carrot virome proved particularly rich in viruses involved in complex mutual interdependencies for aphid transmission such as poleroviruses, umbraviruses and associated satellites, which can be the basis for further investigations of synergistic or antagonistic virus-vector-host relationships.

Pathogenicity characterization of nocardiosis in orange-spotted grouper (Epinephelus coioides) via exposure to nine distinct isolates of Nocardia seriolae and four administrative routes.

Nocardia seriolae causes chronic nocardiosis in various marine and freshwater aquatic animals; however, grouper species have rarely been investigated. This study evaluated the pathogenicity of nocardiosis following N. seriolae infection in the orange-spotted grouper Epinephelus coioides. Nine identified genetic isolates of N. seriolae were tested in vivo using the intraperitoneal method and observed daily for 35 days. The most virulent isolate was then used to evaluate transmission through different routes (intraperitoneal IP, intramuscular IM, oral OR, and immersion IS) in the same fish model and was observed daily for 42 days. The results showed mild variation in virulence among N. seriolae isolates. AOD107132-2 K and OT103003-N11 strains displayed the highest and lowest risk virulence, respectively, based on the accumulation and kinetics of mortality. IM and IP administrations showed an early phase response with early mortality by 5 dpc (30%-100%), while slower kinetics of nocardiosis occurred in the OR and IS routes with slow mortality at 35 dpc (4%-8%). Histopathology revealed typical granulomas, confirming the progression of nocardiosis in the diseased fish. These results provide the basis for further studies on the virulence profile of N. seriolae in Taiwan and a well-suited route of administration in orange-spotted groupers for further prevention development.

Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe

The genomic landscape of Stone Age Europe was shaped by multiple migratory waves and population replacements, but different regions do not all show similar patterns. To refine our understanding of the population dynamics before and after the dawn of the Neolithic, we generated and analyzed genomic sequence data from human remains of 56 individuals from the Mesolithic, Neolithic, and Eneolithic across Central and Eastern Europe. We found that Mesolithic European populations formed a geographically widespread isolation-by-distance zone ranging from Central Europe to Siberia, which was already established 10,000 years ago. We found contrasting patterns of population continuity during the Neolithic transition: people around the lower Dnipro Valley region, Ukraine, showed continuity over 4000 years, from the Mesolithic to the end of the Neolithic, in contrast to almost all other parts of Europe where population turnover drove this cultural change, including vast areas of Central Europe and around the Danube River.

Genetic Incompatibilities and Evolutionary Rescue by Wild Relatives Shaped Grain Amaranth Domestication.

Crop domestication and the subsequent expansion of crops have long been thought of as a linear process from a wild ancestor to a domesticate. However, evidence of gene flow from locally adapted wild relatives that provided adaptive alleles into crops has been identified in multiple species. Yet, little is known about the evolutionary consequences of gene flow during domestication and the interaction of gene flow and genetic load in crop populations. We study the pseudo-cereal grain amaranth that has been domesticated three times in different geographic regions of the Americas. We quantify the amount and distribution of gene flow and genetic load along the genome of the three grain amaranth species and their two wild relatives. Our results show ample gene flow between crop species and between crops and their wild relatives. Gene flow from wild relatives decreased genetic load in the three crop species. This suggests that wild relatives could provide evolutionary rescue by replacing deleterious alleles in crops. We assess experimental hybrids between the three crop species and found genetic incompatibilities between one Central American grain amaranth and the other two crop species. These incompatibilities might have created recent reproductive barriers and maintained species integrity today. Together, our results show that gene flow played an important role in the domestication and expansion of grain amaranth, despite genetic species barriers. The domestication of plants was likely not linear and created a genomic mosaic by multiple contributors with varying fitness effects for today's crops.

Genetic drift versus natural selection affecting the evolution of spectral and functional traits of two key macrophytes: Phragmites australis and Nuphar lutea

Abstract Both genetic and phenotypic intraspecific diversity play a crucial role in the ecological and evolutionary dynamics of organisms. Several studies have compared phenotypic divergence (Pst) and differentiation of neutral loci (Fst) to infer the relative roles of genetic drift and natural selection in population differentiation (Pst–Fst comparison). For the first time, we have assessed and compared the genetic variation and differentiation at the leaf trait level in two key macrophytes, Phragmites australis and Nuphar lutea. To this aim, we quantified and described the genetic structure and phenotypic diversity of both species in five lake systems in north‐central Italy. We then investigated the relative roles of genetic drift and natural selection on leaf trait differentiation (Pst–Fst), assuming that Fst reflects divergence caused only by genetic drift while Pst also incorporates the effects of selective dynamics on the phenotype. In terms of genetic structure, the results for P. australis were in line with those observed for other Italian and European conspecific populations. Conversely, N. lutea showed a more complex genetic structure than expected at the site level, probably due to the combined effect of genetic isolation and its mixed mating system. Both species exhibited high variability in leaf functional traits within and among sites, highlighting a high degree of phenotypic plasticity. Pst–Fst comparisons showed a general tendency towards directional selection in P. australis and a more complex pattern in N. lutea. Indeed, the drivers of phenotypic differentiation in N. lutea showed a variable mix of stabilising and directional selection or neutral divergence at most sites. The prevalence of vegetative over generative reproduction leads P. australis populations to be dominated by a few clones that are well adapted to local conditions, including phenotypes that respond plastically to the environment. In contrast, in N. lutea, the interaction of a mixed mating system and geographical isolation among distant sites tends to reduce the effect of outbreeding depression and provides the genetic basis for adaptive capacity. The first joint analysis of the genetic structure of these two key macrophytes allowed a better understanding of the relative roles of genetic drift and natural selection in the diversification of phenotypic traits within habitats dominated by P. australis and N. lutea.

Urban environment determines population genetics in the green toad, Bufotes viridis

Heavily urbanized areas can hinder dispersal and gene flow between amphibian populations. Given the growth potential of urbanization, it is important to examine how this specific environment shapes their genetic patterns at the local scale. The ability of the European green toad to successfully colonize large human settlements has been convincingly confirmed in the recent past, but little is known about its population genetics under these new conditions. In this study, we examined the effects of the environment on genetic variation, population structure, and the level of gene flow in populations of this amphibian in the city of Košice and the adjacent rural area (eastern Slovakia) using a set of neutral genetic markers. We found that urban populations had lower genetic variability than populations in adjacent rural areas; however, the degree of inbreeding was relatively low in all samples. Genetic differentiation was higher, and gene flow was more restricted in urban area, although geographic distances between sites were significantly less than in rural area (2–4 km versus 6–13 km). Our analyses suggested genetic isolation of urban populations at sites with less suitable habitat for green toads. In contrast, admixture of the population inhabiting the large city park, established on a former floodplain, with all rural populations was likely the result of an intense historical gene flow. The densely developed environment of the other urban sites likely presents a strong barrier to gene flow. The lack of suitable wetland habitat prior to development suggests that these sites were only recently colonized by a limited number of founders. Thus, we found differential effects of the city on the population structure of the green toad. Understanding current local genetic variation and structure is important for future conservation plans in urban environments.

Introgression of non-native mitochondrial haplotypes from farmed to wild Atlantic salmon

Farmed salmon escape and interbreed with wild Atlantic salmon on a large scale. We studied introgression of mitochondrial haplotypes from farmed Atlantic salmon originating from the Eastern Atlantic phylogenetic group to wild salmon of the Barents-White Sea (BWS) phylogenetic group. We find that farmed genetic introgression introduced novel, non-native haplotypes into the BWS phylogenetic group. The mitochondrial genome has important functional effects and is inherited as a haploid from the mother. Hence, the observed introgression across natural genetic barriers is expected to cause long-lasting functional maladaptation of the hybrids in the maternal line. As the use of farmed Atlantic salmon from non-native phylogenetic groups is widespread in aquaculture, the impact on wild Atlantic salmon may be more severe than previously recognized. Our results highlight the ecological risks of releasing non-native wild and domesticated animals.

Patterns of HIV-1 drug resistance among HIV-infected patients receiving first-line antiretroviral therapy in Novosibirsk Region, Russia

Antiretroviral (ARV) drugs have played a vital role in controlling the HIV-1 epidemic; however, some challenges remain. ARV drugs vary in their ability to control HIV infection, displaying differences in treatment-limiting factors and genetic barriers to resistance. The current report assesses the prevalence of HIV-1 drug resistance mutations (DRMs) among patients who failed first-line antiretroviral therapy (ART) and evaluates the genetic barrier of different regimens. The study cohort (n=271) included HIV-infected individuals who visited the Novosibirsk, Russia, HIV/AIDS clinic in 2018-2022. All patients received first-line ART prior to virological failure. Sociodemographic and HIV-related data were collected from medical records and self-reported questionnaires. HIV-1 pol gene sequences were generated, and the presence of HIV-1 DRM was assessed. The genetic barrier to resistance was assessed by combining treatment regimen and adherence data. Nonoptimal ART adherence was identified in 48.3% of patients and correlated with male sex, PWID, unemployment, and rural area residence. Most of the patients with high-level adherence were identified among those who were on TDF+3TC+DTG. HIV-1 DRMs were identified in 54.6% of the patients. The analysis of HIV-1 DRM, ART regimen, and adherence data classified TDF+3TC+DTG and TDF+3TC+LPV/r as treatment regimens with a high genetic barrier, whereas EFV-containing ART was classified as a regimen with a low genetic barrier. The current study delivers results on the efficacy of HIV-1 ART and treatment adherence in real-world practice settings. This report suggests that ART regimens with a high genetic barrier to resistance combined with improved treatment adherence may reduce the transmission of HIV-1 resistant variants.

High frequency of Lamivudine and Telbivudine resistance mutations in hepatitis B virus isolates from human immunodeficiency virus co-infected patients on highly active antiretroviral therapy in Bucaramanga, Colombia.

Hepatitis B virus (HBV) antiviral Resistance-Associated Mutations (RAMs) in human immunodeficiency virus (HIV) coinfected patients undergoing highly active antiretroviral therapy (HAART) are complex and incompletely understood. We aimed to determine the prevalence of HBV coinfection, HBV genotypes, and RAMs in a cohort of people living with HIV (PLWH) in the northeastern region of Colombia. This cross-sectional study was carried out between February 2013 and February 2014. Virological, immunological and HAART data were collected from clinical records. In-house nested PCR and Sanger sequencing of the HBV pol gene were used to identify coinfections, genotypes, RAMs and HBV s antigen (HBsAg) escape mutants. Among 275 PLWH, HBV coinfection was confirmed in 32 patients (11.6%), of whom nine (28.2%) were HBsAg positive (active hepatitis B), and 23 (71.8%) were occult hepatitis B infections (OBI). All HBV sequences (n = 23) belonged to the genotype F3. Among HIV/HBV coinfections, 71.9% had CD4+ T cell counts above 200 cells/mm3 and 37.5% had undetectable HIV viral loads. The RAMs rtL80I, rtL180M, and rtM204V, which confer resistance to Lamivudine/Telbivudine and partially resistant to Entecavir, were found in all HBV isolates. An unknown rt236Y mutation to Tenofovir was also identified. Most patients under HAART received first-generation HBV antiviral therapy with a low genetic barrier to resistance. Antiviral Drug-associated Potential Vaccine-escape Mutations (ADAPVEMs) in the S gene were observed in all isolates ranging from 1-20 amino acid substitutions. However, no vaccine escape mutants were detected. In Conclusion, these findings highlight the importance of HBV molecular screening, antiviral resistance monitoring and new guidelines for PLWH to overcome RAMs and prevent HBV-related liver disease.

Novel siRNA therapeutics demonstrate multi-variant efficacy against SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular vaccinations, have shifted from zero COVID to living with COVID, there is a distinct lack of broad-spectrum direct acting antiviral therapies that maintain efficacy across evolving SARS-CoV-2 variants of concern. This is of most concern for immunocompromised and immunosuppressed individuals who lack robust immune responses following vaccination, and others at risk for severe COVID and long-COVID. RNA interference (RNAi) therapeutics induced by short interfering RNAs (siRNAs) offer a promising antiviral treatment option, with broad-spectrum antiviral capabilities unparalleled by current antiviral therapeutics and a high genetic barrier to antiviral escape. Here we describe novel siRNAs, targeting highly conserved regions of the SARS-CoV-1 and 2 genome of both human and animal species, with multi-variant antiviral potency against eight SARS-CoV-2 lineages - Ancestral VIC01, Alpha, Beta, Gamma, Delta, Zeta, Kappa and Omicron. Treatment with our siRNA resulted in significant protection against virus-mediated cell death in vitro, with >97% cell survival (P < 0.0001), and corresponding reductions of viral nucleocapsid RNA of up to 99.9% (P < 0.0001). When compared to antivirals; Sotrovimab and Remdesivir, the siRNAs demonstrated a more potent antiviral effect and similarly, when multiplexing siRNAs to target different viral regions simultaneously, an increased antiviral effect was observed compared to individual siRNA treatments (P < 0.0001). These results demonstrate the potential for a highly effective broad-spectrum direct acting antiviral against multiple SARS-CoV-2 variants, including variants resistant to antivirals and vaccine generated neutralizing antibodies.

Phylogeography of the red alga Gracilariopsis tenuifrons (Gracilariales) along the Brazilian coast.

Changes in the sea level during the Holocene are regarded as one of the most prevalent drivers of the diversity and distribution of macroalgae in Brazil, influenced by the emergence of the Vitória-Trindade seamount chain (VTC). Gracilariopsis tenuifrons has a wide geographic distribution along the Brazilian coast, from Maranhão state (2°48'64.3" S) to Santa Catarina state (27.5°73'83" S). The knowledge of historical processes affecting diversity may allow the development of conservation strategies in environments against anthropogenic influence. Therefore, knowledge about phylogeography and populational genetic diversity in G. tenuifrons is necessary. Six populations were sampled along the northeastern tropical (Maranhão-MA, Rio Grande do Norte-RN, Alagoas-AL, and Bahia-BA States) and southeastern subtropical (São Paulo "Ubatuba"-SP1 and São Paulo "Itanhaém"-SP2 States) regions along the Brazilian coast. The genetic diversity and structure of G. tenuifrons were inferred using mitochondrial (COI-5P and cox2-3 concatenated) DNA markers. Gracilariopsis tenuifrons populations showed an evident separation between the northeast (from 2°48'64.3" S to 14°18'23" S; 17 haplotypes) and the southeast (from 23°50'14.9" S to 24°20'04.7" S; 10 haplotypes) regions by two mutational steps between them. The main biogeographical barrier to gene flow is located nearby the VTC. The southeast region (São Paulo State) is separated by two subphylogroups (SP1, three haplotypes and SP2, six haplotypes), and Santos Bay (estuary) has been considered a biogeographical barrier between them. The presence of genetic structure and putative barriers to gene flow are in concordance with previous studies reporting biogeographic breaks in the southwest Atlantic Ocean, including the genetic isolation between northeast and southeast regions for red and brown algae in the vicinity of the VTC.

Speciation patterns of related species under the hybrid zone: A case study of three sclerophyllous oaks in the east Himalaya-Hengduan Mountains.

Speciation is often accompanied by frequent gene exchanges, which have been gradually recognized as a common phenomenon in nature. Although gene flow may influence different reproductive isolations, the specific mechanism of the process still requires more experimental evidence, especially in hybrid populations that have no significant differentiation and isolation. To address this challenge, this study aims to elucidate the underlying mechanisms of sympatry and parapatry in related species. Three sclerophyllous oaks (Quercus spinosa, Quercus aquifolioides and Quercus rehderiana), which are mainly distributed in the sympatry/parapatry of the East Himalaya-Hengduan Mountains and adjacent regions, were used to explore the population dynamics and evolutionary history. Based on 12,420 genome-wide single nucleotide polymorphism datasets, gene flow detection showed that the three species did not present any obvious genetic barriers. Evolutionary analysis indicated that the three species diverged during the Tertiary Period, and no migration events occurred in the early stages of species divergence. Combined with the data of 19 ecological factors, geological movements and climatic turbulence caused the rapid radiated differentiation of the three species during the Neocene, and similar selective pressures resulted in the same evolutionary pattern based on demographic history analysis. In addition, the predicted niche occupancy profiles and Generalized Dissimilarity Modelling revealed that the three species occupied distinct niches and had significant differences in ecological adaptation, which may explain the specific morphological characteristics of the different species. Therefore, we believe that the populations of the three related species underwent adaptive evolution in different habitats during the early stages of divergence. This study provides new experimental evidence of the formation patterns of parallel speciation.

Virus-like transposons cross the species barrier and drive the evolution of genetic incompatibilities.

Horizontal gene transfer, the movement of genetic material between species, has been reported across all major eukaryotic lineages. However, the underlying mechanisms of transfer and their impact on genome evolution are still poorly understood. While studying the evolutionary origin of a selfish element in the nematode Caenorhabditis briggsae, we discovered that Mavericks, ancient virus-like transposons related to giant viruses and virophages, are one of the long-sought vectors of horizontal gene transfer. We found that Mavericks gained a novel herpesvirus-like fusogen in nematodes, leading to the widespread exchange of cargo genes between extremely divergent species, bypassing sexual and genetic barriers spanning hundreds of millions of years. Our results show how the union between viruses and transposons causes horizontal gene transfer and ultimately genetic incompatibilities in natural populations.

Expansion processes of two emblematic Luehdorfia butterflies across the Japanese archipelago

AbstractAimAdaptation to local environments has been considered a driving force of ecological speciation. Previous phylogenetic studies at higher taxonomic levels have strongly suggested that herbivore diversification occurs through local adaptation to host plants. However, whether similar mechanisms contribute to within‐species diversification remains poorly understood. We reconstructed species expansion processes using the phylogenetic relationships between two Luehdorfia butterflies and their host plants and tested the local adaptation hypothesis during species diversification.LocationJapanese archipelago.TaxaLuehdorfia japonica and L. puziloi.MethodsWe analysed mitochondrial DNA and single‐nucleotide polymorphisms to trace the expansion processes of two species in the Japanese archipelago. We analysed data collected during trans‐host plant feeding experiments to test for local host plant adaptation in L. japonica.ResultsLuehdorfia japonica differentiated 17.0 million years ago (MYA) from a group of four Luehdorfia species in East Asia, and L. puziloi differentiated 13.3 MYA from the remaining three species. We observed several genetic groups in both species, reflecting geographical differences among populations. Some host plants had detrimental effects on the pupation rates of L. japonica, demonstrating the presence of genetic barriers between populations of this species.Main ConclusionsAlthough these two sibling species were influenced by the geological formation of the Japanese archipelago, their present population structures differ greatly: L. japonica expanded its distribution and adapted to local host plants along at least four expansion routes independent of host plant phylogeny, and L. puziloi exhibited a more isolated population structure and was less strongly influenced by gene flow among populations. These results suggest that both isolation by distance and isolation by adaptation have been important drivers resulting in the present‐day population structure of L. japonica. Unidirectional gene flow through local adaptation to the host plant may have played a role in initial speciation.

Genetic counselors' research dissemination practices and attitudes.

Benefits have been demonstrated to disseminating aggregate research results to all relevant audiences, including study participants. Despite this, many health researchers face barriers in dissemination to broad audiences and returning aggregate results to participants is not commonly practiced. Due to their research presence and training in communication, genetic counselors can lead in implementing best practices in this area. We explored genetic counselors' current practices and opinions regarding educating study participants and wider audiences of research findings. We distributed a survey of 32 multiple-choice and open-ended questions to National Society of Genetics Counselors (NSGC) and Canadian Association of Genetic Counsellors (CAGC) members. Most respondents (90.1%, n = 128/142) identified with a responsibility to disseminate their research findings to a broad audience and identified several associated benefits. All respondents saw value in communicating aggregate results to study participants, although over half (53.2%, n = 66/124) had never done so. Genetic counselors reported resource and knowledge barriers to research dissemination. Despite expertise in education and communication, genetic counselors face similar barriers as other researchers toward broad dissemination of research. Formal training and professional guidelines specific to research dissemination practices will equip genetic counselors to reach broader audiences and maximize the impact of research findings.

Kaempferol therapy improved MC903 induced-atopic dermatitis in a mouse by suppressing TSLP, oxidative stress, and type 2 inflammation

BackgroundAtopic dermatitis is a common skin disease caused by genetic susceptibility, environmental factors, immune response, and skin barrier dysfunction. Kaempferol is a natural flavonoid widely found in tea, vegetables, and fruits and has been reported to have excellent anti-inflammation activity. However, the therapeutic effect of kaempferol on atopic dermatitis is unclear. ObjectiveThis study aimed to elucidate the effect of kaempferol on skin inflammation in atopic dermatitis. MethodsThe suppressive effect of kaempferol administration on skin inflammation was examined using MC903-induced atopic dermatitis-like skin inflammation mouse model. Quantification of skin dermatitis and transepidermal water loss was performed. A histopathological study was performed to examine thymic stromal lymphopoietin expression, cornified envelope proteins such as filaggrin, loricrin, and involucrin, and the numbers of infiltrating inflammatory cells, including lymphocytes, macrophages, and mast cells in the dermatitis area. The expressions of IL-4 and IL-13 were investigated by qPCR and flow cytometry analysis using skin tissues. The expression of HO-1 was investigated by western blot and qPCR. ResultsKaempferol therapy significantly suppressed MC903-induced dermatitis, TEWL, TSLP, and HO-1 expression, and infiltration of inflammatory cells. Kaempferol therapy improved the decreased expressions of filaggrin, loricrin, and involucrin in MC903-induced dermatitis skin site. The expressions of IL-4, and IL-13 were partially decreased in kaempferol-treated mice. ConclusionKaempferol might improve MC903-induced dermatitis via suppression of type 2 inflammation and improvement of barrier dysfunction by inhibition of TSLP expression and oxidative stress. Kaempferol might have the potential to be a new treatment for atopic dermatitis.

Treatment-emergent reverse transcriptase resistance during antiretroviral therapy with bictegravir, tenofovir alafenamide, and emtricitabine: A case series.

Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) is a complete regimen for the treatment of HIV with a high barrier to resistance and few reported cases of treatment failure. We present three cases of treatment-emergent resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in patients with suboptimal treatment adherence and assess whether the resistance-associated mutations were present before BIC/TAF/FTC initiation or emerged during therapy. We used genotypic drug resistance testing by Sanger sequencing to identify emergent resistance mutations in plasma viral load specimens collected after combination antiretroviral therapy initiation in all participants. Additionally, we performed ultra-deep sequencing by Illumina MiSeq on the earliest available plasma HIV-1 viral load specimen and on any available specimens closest in time to the initiation of BIC/TAF/FTC therapy to identify low-abundance resistance mutations present in the viral quasispecies. All three participants developed NRTI resistance after prolonged exposure and incomplete adherence to BIC/TAF/FTC. The T69N, K70E, M184I, and/or T215I mutations identified in clinical samples at the time of virological failure were not present on deep sequencing of either baseline samples or samples collected before BIC/TAF/FTC initiation. Despite a generally high genetic barrier to resistance, NRTI resistance-associated mutations may emerge during therapy with BIC/TAF/FTC in the setting of suboptimal adherence.

Genomic analyses reveal dead-end hybridization between two deeply divergent kiwifruit species rather than homoploid hybrid speciation.

Despite the importance of hybridization in evolution, the evolutionary consequence of homoploid hybridizations in plants remains poorly understood. Specially, homoploid hybridization events have been rarely documented due to a lack of genomic resources and methodological limitations. Actinidia zhejiangensis was suspected to have arisen from hybridization of Actinidia eriantha and Actinidia hemsleyana or Actinidia rufa. However, this species was very rare in nature and exhibited sympatric distribution with its potential parent species, which implied it might be a spontaneous hybrid of ongoing homoploid hybridization. Here, we illustrate the dead-end homoploid hybridization and genomic basis of isolating barriers between A. eriantha and A. hemsleyana through whole genome sequencing and population genomic analyses. Chromosome-scale genome assemblies of A. zhejiangensis and A. hemsleyana were generated. The chromosomes of A.zhejiangensis are confidently assigned to the two haplomes, and one of them originates from A. eriantha and the other originates from A. hemsleyana. Whole genome resequencing data reveal that A. zhejiangensis are mainly F1 hybrids of A. hemsleyana and A. eriantha and gene flow initiated about 0.98 million years ago, implying both strong genetic barriers and ongoing hybridization between these two deeply divergent kiwifruit species. Five inversions containing genes involved in pollen germination and pollen tube growth might account for the fertility breakdown of hybrids between A. hemsleyana and A. eriantha. Despite its distinct morphological traits and long recurrent hybrid origination, A. zhejiangensis does not initiate speciation. Collectively, our study provides new insights into homoploid hybridization in plants and provides genomic resources for evolutionary and functional genomic studies of kiwifruit.

Adult-Onset Neuroepidemiology in Finland: Lessons to Learn and Work to Do.

Finland is a relatively small genetic isolate with a genetically non-homogenous population. Available Finnish data on neuroepidemiology of adult-onset disorders are limited, and this paper describes the conclusions that can be drawn and their implications. Apparently, Finnish people have a (relatively) high risk of developing Unverricht-Lundborg disease (EPM1), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Spinal muscular atrophy, Jokela type (SMAJ) and adult-onset dystonia. On the other hand, some disorders, such as Friedreich's ataxia (FRDA) and Wilson's disease (WD), are almost absent or completely absent in the population. Valid and timely data concerning even many common disorders, such as stroke, migraine, neuropathy, Alzheimer's disease and Parkinson's disease, are unavailable, and there are virtually no data on many less-common neurological disorders, such as neurosarcoidosis or autoimmune encephalitides. There also appear to be marked regional differences in the incidence and prevalence of many diseases, suggesting that non-granular nationwide data may be misleading in many cases. Concentrated efforts to advance neuroepidemiological research in the country would be of clinical, administrative and scientific benefit, but currently, all progress is blocked by administrative and financial obstacles.