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Abstract Thyroid dyshormonogenesis (TDH) is responsible for 15%–25% of congenital hypothyroidism (CH) cases. Pathogenetic variants of this common inherited endocrine disorders vary geographically. Unraveling the genetic underpinnings of TDH is essential for genetic counseling and precise therapeutic strategies. This study aims to identify genetic variants associated with TDH in Southern Taiwan using whole exome sequencing (WES). We included CH patients diagnosed through newborn screening at a tertiary medical center from 2011 to 2022. Permanent TDH was determined based on imaging evidence of bilateral thyroid structure and the requirement for continuous medication beyond 3 years of age. Genomic DNA extracted from blood was used for exome library construction, and pathogenic variants were detected using an in‐house algorithm. Of the 876 CH patients reviewed, 121 were classified as permanent, with 47 (40%) confirmed as TDH. WES was conducted for 45 patients, and causative variants were identified in 32 patients (71.1%), including DUOX2 (15 cases), TG (8 cases), TSHR (7 cases), TPO (5 cases), and DUOXA2 (1 case). Recurrent variants included DUOX2 c.3329G>A, TSHR c.1349G>A, TG c.1348delT, and TPO c.2268dupT. We identified four novel variants based on genotype, including TSHR c.1135C>T, TSHR c.1349G>C, TG c.2461delA, and TG c.2459T>A. This study underscores the efficacy of WES in providing definitive molecular diagnoses for TDH. Molecular diagnoses are instrumental in genetic counseling, formulating treatment, and developing management strategies. Future research integrating larger population cohorts is vital to further elucidate the genetic landscape of TDH.

Abstract The preservation of genetic variation is fundamental in biodiversity conservation, yet its importance for population viability remains contentious. Mixed‐source reintroductions, where individuals are translocated into a single vacant habitat from multiple genetically divergent and often depauperate populations, provide an opportunity to evaluate how genetic variation and hybridization influence individual and relative population fitness. Population genetic theory predicts that individuals with higher genetic variation and hybrids among populations should have higher fitness. We tested these two hypotheses by analyzing individual and population‐scale data for westslope cutthroat trout (Oncorhynchus clarkii lewisi) in four mixed‐source reintroductions. We observed more hybrid and fewer nonhybrid offspring than expected across four independent mixed‐source reintroductions. We also found clear evidence that heterozygosity influenced individual reproductive and relative population fitness. Overall, we found a strong, positive relationship between genetic variation, hybridization, and transplant fitness, emphasizing the importance of genetic variation and population mixing in conservation.

Abstract Earth is now experiencing declines in insect abundance and diversity unparalleled in human history. The drivers underlying those declines are many, complex, and incompletely known. Here, using a natural experiment, we report the first test of the hypothesis that forest defoliation by an invasive outbreak insect compromises the fitness of a native insect via damage‐induced increases in toxicity of the forest canopy. We demonstrate that defoliation by the invasive spongy moth (Lymantria dispar) elicits an average 8.4‐fold increase in foliar defense expression among aspen (Populus tremuloides) genotypes. In turn, elevated defense dramatically reduces survivorship, feeding, and growth of a charismatic mega moth (Anthereae polyphemus). This work suggests that changes to the phytochemical landscape of forests, mediated by invasive outbreak insects, are likely to negatively impact native insects, with potential repercussions for community diversity and ecosystem function across expansive scales.

Abstract Background and Aim Celiac disease (CD) has proinflammatory and pathogenic immune responses to gluten in intestinal tissue, leading to structural changes in the mucosa of the small intestine. The association of human leukocyte antigen (HLA)‐DQ2 and DQ8 genotypes with CD has been previously reported. This test has a negative predictive value close to 100%, so its main purpose is to rule out the detection of CD completely or almost completely. There is limited information regarding HLA‐DQ4/5 in CD. This study was conducted to determine the HLA‐DQ4/5 genotypes in a group of Southwestern Iranian children with CD. Methods We conducted a case‐control study in Southwest Iran involving 100 participants, employing a nonprobabilistic sampling method. Samples were taken from participants' oral buccal mucosa at Imam Sajjad Hospital of Yasuj, Iran. Then DNA was extracted from these samples and used to determine the frequency of HLA‐DQ4/5 genotypes through Sequence‐Specific Primer‐Polymerase Chain Reaction assay. SPSS 20 was utilized for statistical analyses. Results Fifty diagnosed patients with CD (high anti‐tissue transglutaminase [tTG]‐IgA level [upper limit of normal] with pathological findings of Marsh III) and 50 non‐CD individuals (normal anti‐tTG‐IgA level and normal total IgA level) were enrolled in the study from August 5, 2022 to October 15, 2023. Findings showed that the DQ4a*4b allele has the highest frequency in the CD samples (78%, p 9.5) (p

Abstract Background A variant in the canine phosphodiesterase (PDE) 5A gene (PDE5A:E90K) is associated with decreased concentrations of circulating cyclic guanosine monophosphate (cGMP) and response to PDE5 inhibitor treatment. Pimobendan is a PDE inhibitor recommended for medical treatment of certain stages of myxomatous mitral valve disease (MMVD) in dogs. Hypothesis PDE5A:E90K polymorphism attenuates the inhibitory effect of pimobendan on in vitro platelet aggregation and increases basal platelet aggregation in Cavalier King Charles Spaniels (CKCS). Selected clinical variables (MMVD severity, sex, age, hematocrit, platelet count in platelet‐rich plasma [PRP], and echocardiographic left ventricular fractional shortening [LV FS]) will not show an association with results. Animals Fifty‐two privately owned CKCS with no or preclinical MMVD. Methods Using blood samples, we prospectively assessed PDE5A genotype using Sanger sequencing and adenosine diphosphate‐induced platelet aggregation response (area under the curve [AUC], maximal aggregation [MaxA], and velocity [Vel]) with and without pimobendan using light transmission aggregometry. Dogs also underwent echocardiography. Results Pimobendan inhibited platelet function as measured by AUC, MaxA, and Vel at a concentration of 10 μM (P

Abstract Rapid environmental change presents a significant challenge to the persistence of natural populations. Rapid adaptation that increases population growth, enabling populations that declined following severe environmental change to grow and avoid extinction, is called evolutionary rescue. Numerous studies have shown that evolutionary rescue can indeed prevent extinction. Here, we extend those results by considering the demographic history of populations. To evaluate how demographic history influences evolutionary rescue, we created 80 populations of red flour beetle, Tribolium castaneum, with three classes of demographic history: diverse populations that did not experience a bottleneck, and populations that experienced either an intermediate or a strong bottleneck. We subjected these populations to a new and challenging environment for six discrete generations and tracked extinction and population size. Populations that did not experience a bottleneck in their demographic history avoided extinction entirely, while more than 20% of populations that experienced an intermediate or strong bottleneck went extinct. Similarly, among the extant populations at the end of the experiment, adaptation increased the growth rate in the novel environment the most for populations that had not experienced a bottleneck in their history. Taken together, these results highlight the importance of considering the demographic history of populations to make useful and effective conservation decisions and management strategies for populations experiencing environmental change that pushes them toward extinction.

Abstract Drug development is a long and costly process, with a high degree of uncertainty from the identification of a drug target to its market launch. Targeted drugs supported by human genetic evidence are expected to enter phase II/III clinical trials or be approved for marketing more quickly, speeding up the drug development process. Currently, genetic data and technologies such as genome‐wide association studies (GWAS), whole‐exome sequencing (WES), and whole‐genome sequencing (WGS) have identified and validated many potential molecular targets associated with diseases. This review describes the structure, molecular biology, and drug development of human genetics‐based validated beneficial loss‐of‐function (LOF) mutation targets (target mutations that reduce disease incidence) over the past decade. The feasibility of eight beneficial LOF mutation targets (PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, and INHBE) as targets for drug discovery is mainly emphasized, and their research prospects and challenges are discussed. In conclusion, we expect that this review will inspire more researchers to use human genetics and genomics to support the discovery of novel therapeutic drugs and the direction of clinical development, which will contribute to the development of new drug discovery and drug repurposing.

Abstract The western Terai Arc Landscape (wTAL) in Uttarakhand, India, marks the range limit for the Asian elephant in north‐western India. This region has been impacted by land‐use changes and infrastructure expansion for the last seven decades. To evaluate the impact of habitat deterioration on the population structure of elephants in the region, we characterized their genetic diversity and local genetic structure using mitochondrial (D loop) and nuclear DNA (microsatellites; n = 15) markers. We used tissue samples of 114 elephants from five different sub‐populations, collected between 2005 and 2014. The genetic variation was moderate (HO = 0.49–0.55) compared with other Indian elephant populations. Two mtDNA haplotypes were identified without strong spatial patterns across wTAL. Bayesian individual‐based clustering algorithm identified two genetic clusters (K = 2) with high admixture (50% at Q

Abstract Genetic diversity is the raw material of evolution, yet the reasons why it varies among species remain poorly understood. While studies at deeper phylogenetic scales point to the influence of life history traits on genetic diversity, it appears to be more affected by population size but less predictable at shallower scales. We used proxies for population size, mutation rate, direct selection, and linked selection to test factors affecting genetic diversity within a diverse assemblage of Neotropical salamanders, which vary widely for these traits. We estimated genetic diversity of noncoding loci using ddRADseq and coding loci using RNAseq for an assemblage of Neotropical salamanders distributed from northern Mexico to Costa Rica. Using ddRADseq loci, we found no significant association with genetic diversity, while for RNAseq data we found that environmental heterogeneity and proxies of population size predict a substantial portion of the variance in genetic diversity across species. Our results indicate that diversity of coding loci may be more predictable than that of noncoding loci, which appears to be mostly unpredictable at shallower phylogenetic scales. Our results suggest that coding loci may be more appropriate for genetic diversity estimates used in conservation planning because of the lack of any association between the variables we used and genetic diversity of noncoding loci.

Abstract Long‐term blood pressure variability (BPV) is a risk factor for cardiovascular diseases, dementia, and stroke. However, its genetic architecture is not fully understood. This study aims to explore its genetic factors and provide more evidence on the mechanisms and further pathological study of BPV. The genome‐wide association study (GWAS) is based on the UK Biobank cohort. There were four data collection rounds from 2006 to 2020, and 9370 participants with more than three blood pressure measurements were included. They had a median age of 55 and a male percentage of 50.1%. The phenotypes (BPV) were calculated by four methods and the genetic data contains 6 884 260 single nucleotide polymorphisms (SNPs) after imputation and quality control. A linear regression model was performed with adjustments for sex, age, genotype array, and a significant principal component. Subgroup analysis was performed on hypertension‐free participants. The significant and suggestive significant P thresholds were set as 5 × 10−8 and 1 × 10−6. Six genetic loci (BAD, CCDC88B, GPR137, PLCB3, RPS6KA4 for systolic BPV, and WWC2 for diastolic BPV) were identified by coding region SNPs at the suggestive significant P threshold (1 × 10−6). Among them, gene CCDC88B and RPS6KA4 reached the significant P threshold (5 × 10−8), with the strongest signal of SNP rs1229536170 (P = 6.36 × 10−8, β = –.29). The annotation results indicate that genes CCDC88B, GPR137, RPS6KA4, and BAD are associated with long‐term SBPV. Their functions of inflammation, epithelial dysfunction, and apoptosis are related to artery stiffness, which was reported as potential mechanisms of BPV.

Abstract Evaluating the contributions of geographic distance and environmental heterogeneity to the genetic divergence can inform the demographic history and responses to environmental change of natural populations. The isolation‐by‐distance (IBD) reveals that genetic differentiation among populations increases with geographic distance, while the isolation‐by‐environment (IBE) assumes a linear relationship between genetic variation and environmental differences among populations. Here, we sampled and genotyped 330 individuals from 18 natural populations of Cephalotaxus oliveri throughout the species' distribution. Twenty‐eight EST‐SSR markers were applied to analyze population genetics, for the investigation of the driving factors that shaped spatial structure. In addition, we identified the outlier loci under positive selection and tested their association with environmental factors. The results showed a moderate genetic diversity in C. oliveri and high genetic differentiation among populations. Population structure analyses indicated that 18 populations were clustered into two major groups. We observed that the genetic diversity of central populations decreased and the genetic differentiation increased towards the marginal populations. Additionally, the signatures of IBD and IBE were detected in C. oliveri, and IBE provided a better contribution to genetic differentiation. Six outlier loci under positive selection were demonstrated to be closely correlated with environmental variables, among which bio8 was associated with the greatest number of loci. Genetic evidence suggests the consistency of the central‐marginal hypothesis (CMH) for C. oliveri. Furthermore, our results suggest that temperature‐related variables played an important role in shaping genetic differentiation.

Abstract In tree species, genomic prediction offers the potential to forecast mature trait values in early growth stages, if robust marker–trait associations can be identified. Here we apply a novel multispecies approach using genotypes from a new genotyping array, based on 20,795 single nucleotide polymorphisms (SNPs) from three closely related pine species (Pinus sylvestris, Pinus uncinata and Pinus mugo), to test for associations with growth and phenology data from a common garden study. Predictive models constructed using significantly associated SNPs were then tested and applied to an independent multisite field trial of P. sylvestris and the capability to predict trait values was evaluated. One hundred and eighteen SNPs showed significant associations with the traits in the pine species. Common SNPs (MAF > 0.05) associated with bud set were only found in genes putatively involved in growth and development, whereas those associated with growth and budburst were also located in genes putatively involved in response to environment and, to a lesser extent, reproduction. At one of the two independent sites, the model we developed produced highly significant correlations between predicted values and observed height data (YA, height 2020: r = 0.376, p

Abstract Conservation translocations have become an important management tool, particularly for large wildlife species such as the lion (Panthera leo). When planning translocations, the genetic background of populations needs to be taken into account; failure to do so risks disrupting existing patterns of genetic variation, ultimately leading to genetic homogenization, and thereby reducing resilience and adaptability of the species. We urge wildlife managers to include knowledge of the genetic background of source/target populations, as well as species‐wide patterns, in any management intervention. We present a hierarchical decision‐making tool in which we list 132 lion populations/lion conservation units and provide information on genetic assignment, uncertainty and suitability for translocation for each source/target combination. By including four levels of suitability, from ‘first choice’ to ‘no option’, we provide managers with a range of options. To illustrate the extent of international trade of lions, and the potential disruption of natural patterns of intraspecific diversity, we mined the CITES Trade Database for estimated trade quantities of live individuals imported into lion range states during the past 4 decades. We identified 1056 recorded individuals with a potential risk of interbreeding with wild lions, 772 being captive‐sourced. Scoring each of the records with our decision‐making tool illustrates that only 7% of the translocated individuals were ‘first choice’ and 73% were ‘no option’. We acknowledge that other, nongenetic factors are important in the decision‐making process, and hence a pragmatic approach is needed. A framework in which source/target populations are scored based on suitability is not only relevant to lion, but also to other species of wildlife that are frequently translocated. We hope that the presented overview supports managers to include genetics in future management decisions and contributes towards conservation of the lion in its full diversity.

Abstract The impact of elevated CO2 (eCO2) on soybean productivity is essential to the global food supply because it is the world's leading source of vegetable proteins. This study aimed to understand the yield responses and nutritional impact under free‐air CO2 enrichment (FACE) conditions of soybean genotypes. Here we report that grain yield increased by 46.9% and no reduction in harvest index was observed among soybean genotypes. Elevated CO2 improved the photosynthetic carbon assimilation rate, leaf area, plant height, and aboveground biomass at vegetative and pod filling stages. Besides the positive effects on yield parameters, eCO2 differentially affected the overall grain quality. The levels of calcium (Ca), phosphorous (P), potassium (K), magnesium (Mg), manganese (Mn), iron (Fe), boron (B), and zinc (Zn) grain minerals decreased by 22.9, 9.0, 4.9, 10.1, 21.3, 28.1, 18.5, and 25.9% under eCO2 conditions, respectively. Soluble sugars and starch increased by 9.1 and 16.0%, respectively, phytic acid accumulation increased by 8.1%, but grain protein content significantly decreased by 5.6% across soybean genotypes. Furthermore, the antioxidant activity decreased by 36.9%, but the total phenolic content was not affected by eCO2 conditions. Genotypes, such as Winsconsin Black, Primorskaja, and L‐117, were considered the most responsive to eCO2 in terms of yield enhancement and less affected in the nutritional quality. Our results confirm the existence of genetic variability in soybean responses to eCO2, and differences between genotypes in yield improvement and decreased sensitivity to eCO2 in terms of grain quality loss could be included in future soybean selection to enable adaptation to climate change.

The humoral response is complex and involves multiple cellular populations and signaling pathways. Bacterial and viral infections, as well as immunization regimens, can trigger this type of response, promoting the formation of microanatomical cellular structures called germinal centers (GCs). GCs formed in secondary lymphoid organs support the differentiation of high-affinity plasma cells and memory B cells. There is growing evidence that the quality of the humoral response is influenced by genetic variants. Using 12 genetically divergent mouse strains, we assessed the impact of genetics on GC cellular traits. At steady state, in the spleen, lymph nodes and Peyer's patches, we quantified GC B cells, plasma cells and follicular helper T cells. These traits were also quantified in the spleen of mice following immunization with a foreign antigen, namely, sheep red blood cells, in addition to the number and size of GCs. We observed both strain- and organ-specific variations in cell type abundance, as well as for GC number and size. Moreover, we find that some of these traits are highly heritable. Importantly, the results of this study inform on the impact of genetic diversity in shaping the GC response and identify the traits that are the most impacted by genetic background., (© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Local adaptation is common in plant species, and knowing whether a population is locally adapted has fundamental and applied relevance. However, local adaptation in tropical plants remains largely less studied, and covering this gap is not simple since reciprocal transplantation - the gold standard for detecting local adaptation - is not feasible for most species. Here, we combined genetic, climatic and phenotypic data to investigate ecotypic differentiation, an important aspect of local adaptation, in coastal and inland populations of the orchid Epidendrum fulgens Brongn., a long-lived tropical plant for which reciprocal transplantation would not be feasible. We used nine microsatellite markers to estimate genetic divergence between inland and coastal populations. Moreover, occurrence data and climate data were used to test for differences in the realized niche of those populations. Finally, we assessed saturated water content, leaf specific area, height, and stomatal density in common garden and in situ to investigate the effects of ecotypic differentiation and plasticity on the phenotype. Coastal and inland groups' niches do not overlap, the former occupying a wetter and warmer area. However, this differentiation does not seem to be driven by ecotypic differentiation since there was no positive correlation between genetic structure and climate dissimilarity. Moreover, specific leaf area and leaf saturated water content, which are important phenotypic traits related to soil fertility and drought stress, were rather plastic. We conclude that ecotypic differentiation is absent, since phenotypic plasticity is an important mechanism explaining the niche broadness of this species., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Objective: Our objective was to evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH)-associated genes among patients with systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS)., Methods: Targeted sequencing of HLH genes (LYST, PRF1, RAB27A, STX11, STXBP2, UNC13D) was performed in patients with sJIA from an established cohort. Sequence data from control participants were obtained in silico (database of Genotypes and Phenotypes: phs000280.v8.p2). Rare variant association testing (RVT) was performed with sequence kernel association test package. Significance was defined as P < 0.05 after 100,000 permutations., Results: Sequencing data from 524 sJIA cases were jointly called and harmonized with exome-derived target data from 3,000 controls. Quality control operations produced a set of 480 cases and 2,924 ancestrally matched control participants. RVT of cases and controls revealed a significant association with rare protein-altering variants (minor allele frequency [MAF] < 0.01) of STXBP2 (P = 0.020) and ultrarare variants (MAF < 0.001) of STXBP2 (P = 0.006) and UNC13D (P = 0.046). A subanalysis of 32 cases with known MAS and 90 without revealed a significant difference in the distribution of rare UNC13D variants (P = 0.0047) between the groups. Additionally, patients with sJIA more often carried two or more HLH variants than did controls (P = 0.007), driven largely by digenic combinations involving LYST., Conclusion: We identified an enrichment of rare HLH variants in patients with sJIA compared with controls, driven by STXBP2 and UNC13D. Biallelic variation in HLH genes was associated with sJIA, driven by LYST. Only UNC13D displayed enrichment in patients with MAS. This suggests that HLH variants may contribute to the pathophysiology of sJIA, even without MAS., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Osmoregulation, the physiological regulation of water and ion balance, is vital for the survival of both aquatic and terrestrial insects. In freshwater aquatic insects, such as those within the Lampyridae family, this function is important due to the natural variation of aquatic habitats. Aquaporins play a key role in this process by facilitating the rapid transport of water molecules across cell membranes, maintaining cellular water balance, and adapting to changes in external salinity. In this study, I investigate the genetic diversity and expression levels of aquaporins in Elateroidea, particularly focusing on the Lampyridae family, using transcriptomic data and in silico analyses. The results reveal the diversity of aquaporins and compare gene expression patterns between freshwater aquatic Lampyridae and terrestrial Elateroidea species, such as Lycidae, Phengodidae, and Elateridae. Phylogenetic analyses identify seven distinct clades of aquaporins and uncovered gene duplication events related to the diversification of Elateridae and Lampyridae. A comparative abundance analysis indicated higher aquaporin expression in aquatic fireflies, aligning with the need for efficient osmoregulation in aquatic environments. Additionally, stage-specific expression patterns in Aspisoma lineatum (Neotropical firefly) and Aquatica lateralis (Paleartic firefly) suggest species-specific strategies for coping with osmotic challenges during development. This study provides insights into the evolutionary adaptations of aquaporins in Elateroidea, highlighting their importance in both aquatic and terrestrial insect physiology., (© 2024 Wiley Periodicals LLC.)

Premise: A key goal of evolutionary biologists is to understand how and why genetic variation is partitioned within species. In the yellow monkeyflower, Mimulus guttatus (syn. Erythranthe guttata), coastal perennial populations constitute a single genetically and morphologically differentiated ecotype compared to inland M. guttatus populations. While the coastal ecotype's distinctiveness has now been well documented, there is also environmental variation across the ecotype's range that could drive more continuous differentiation among its component populations., Methods: Based on previous observations of a potential cline within this ecotype, we quantified plant height, among other traits, across coastal perennial accessions from 74 populations in a greenhouse common garden experiment. To evaluate potential drivers of the relationship between trait variation and latitude, we regressed height against multiple climatic factors, including temperature, precipitation, and coastal wind speeds. We also accounted for exposure to the open ocean in all analyses., Results: Multiple traits were correlated with latitude of origin, but none more than plant height. Height was negatively correlated with latitude, and plants directly exposed to the open ocean were shorter than those protected from coastal winds. Further analyses revealed that height was correlated with climatic factors (precipitation, temperature, and wind speeds) that were autocorrelated with latitude. We hypothesize that one or more of these climatic factors drove the evolution of latitudinal clinal variation within the coastal ecotype., Conclusions: Overall, our study illustrates the complexity of how the distribution of environmental variation can simultaneously drive the evolution of both distinct ecotypes and continuous clines within those ecotypes., (© 2024 The Author(s). American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Diversity is the cornerstone of the adaptive immune system, crucial for its effectiveness against constantly evolving pathogens that pose threats to higher vertebrates. Accurately measuring and interpreting this diversity presents challenges for immunologists, as changes in diversity and clonotype composition can tip the balance between protective immunity and autoimmunity. In this review, we present the current methods commonly used to measure diversity from single-cell T-cell receptor and B-cell receptor sequencing. We also discuss two case studies where single-cell sequencing and diversity estimations have led to breakthroughs in autoimmune disease discovery and therapeutic innovation, and reflect upon the necessity and importance of accurately defining and measuring lymphocyte diversity in these contexts., (© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Premise: Globally, barriers triggered by climatic changes have caused habitat fragmentation and population allopatric divergence. Across North America, oscillations during the Quaternary have played important roles in the distribution of wildlife. Notably, diverse plant species from the Baja California Peninsula in western North America, isolated during the Pleistocene glacial-interglacial cycles, exhibit strong genetic structure and highly concordant divergent lineages across their ranges. A representative plant genus of the peninsula is Yucca, with Y. valida having the widest range. Although a dominant species, it has an extensive distribution discontinuity between 26° N and 27° N, suggesting restricted gene flow. Moreover, historical distribution models indicate the absence of an area with suitable conditions for the species during the Last Interglacial, making it an interesting model for studying genetic divergence., Methods: We assembled 4411 SNPs from 147 plants of Y. valida throughout its range to examine its phylogeography to identify the number of genetic lineages, quantify their genetic differentiation, reconstruct their demographic history and estimate the age of the species., Results: Three allopatric lineages were identified based on the SNPs. Our analyses support that genetic drift is the driver of genetic differentiation among these lineages. We estimated an age of less than 1 million years for the common ancestor of Y. valida and its sister species., Conclusions: Habitat fragmentation caused by climatic changes, low dispersal, and an extensive geographical range gap acted as cumulative mechanisms leading to allopatric divergence in Y. valida., (© 2024 Botanical Society of America.)

Abstract The phenotypic space encompasses the assemblage of trait combinations yielding well‐suited integrated phenotypes. At the population level, understanding the phenotypic space structure requires the quantification of among‐ and within‐population variations in traits and the correlation pattern among them. Here, we studied the phenotypic space of the annual plant Diplotaxis acris occurring in hyperarid deserts. Given the advance of warming and aridity in vast regions occupied by drylands, D. acris can indicate the successful evolutionary trajectory that many other annual plant species may follow in expanding drylands. To this end, we conducted a greenhouse experiment with 176 D. acris individuals from five Saudi populations to quantify the genetic component of variation in architectural and life history traits. We found low among‐population divergence but high among‐individual variation in all traits. In addition, all traits showed a high degree of genetic determination in our study experimental conditions. We did not find significant effects of recruitment and fecundity on fitness. Finally, all architectural traits exhibited a strong correlation pattern among them, whereas for life history traits, only higher seed germination implied earlier flowering. Seed weight appeared to be an important trait in D. acris as individuals with heavier seeds tended to advance flowering and have a more vigorous branching pattern, which led to higher fecundity. Population divergence in D. acris might be constrained by the severity of the hyperarid environment, but populations maintain high among‐individual genetic variation in all traits. Furthermore, D. acris showed phenotypic integration for architectural traits and, to a lesser extent, for life history traits. Overall, we hypothesize that D. acris may be fine‐tuned to its demanding extreme environments. Evolutionary speaking, annual plants facing increasing warming, aridity, and environmental seasonality might modify their phenotypic spaces toward new phenotypic configurations strongly dominated by correlated architectural traits enhancing fecundity and seed‐related traits advancing flowering time.

Abstract The Small East African (SEA) goat are widely distributed in different agro‐ecological zones of Tanzania. We report the genetic diversity, maternal origin, and phylogenetic relationship among the 12 Tanzanian indigenous goat populations, namely Fipa, Songwe, Tanga, Pwani, Iringa, Newala, Lindi, Gogo, Pare, Maasai, Sukuma, and Ujiji, based on the mitochondrial DNA (mtDNA) D‐loop. High haplotype (Hd = 0.9619–0.9945) and nucleotide (π = 0.0120–0.0162) diversities were observed from a total of 389 haplotypes. The majority of the haplotypes (n = 334) belonged to Haplogroup A which was consistent with the global scenario on the genetic pattern of maternal origin of all goat breeds in the world. Haplogroup G comprised of 45 haplotypes drawn from all populations except the Ujiji goat population while Haplogroup B with 10 haplotypes was dominated by Ujiji goats (41%). Tanzanian goats shared four haplotypes with the Kenyan goats and two with goats from South Africa, Namibia, and Mozambique. There was no sharing of haplotypes observed between individuals from Tanzanian goat populations with individuals from North or West Africa. The indigenous goats in Tanzania have high genetic diversity defined by 389 haplotypes and multiple maternal origins of haplogroup A, B, and G. There is a lot of intermixing and high genetic variation within populations which represent an abundant resource for selective breeding in the different agro‐ecological regions of the country.

Abstract Background The neurotransmitter serotonin (5‐HT) affects valvular degeneration and dogs with myxomatous mitral valve disease (MMVD) exhibit alterations in 5‐HT signaling. In Maltese dogs, 3 single nucleotide polymorphisms (SNPs) in the 5‐HT transporter (SERT) gene are suggested to associate with MMVD. Hypothesis/Objectives Determine the association of SERT polymorphisms on MMVD severity and serum 5‐HT concentration in Cavalier King Charles Spaniels (CKCS). Additionally, investigate the association between selected clinical and hematologic variables and serum 5‐HT and assess the correlation between HPLC and ELISA measurements of serum 5‐HT. Animals Seventy‐one CKCS (42 females and 29 males; 7.8 [4.7;9.9] years (median [Q1;Q3])) in different MMVD stages. Methods This prospective study used TaqMan genotyping assays to assess SERT gene polymorphisms. Neurotransmitter concentrations were assessed by HPLC and ELISA. Results TaqMan analyses identified none of the selected SERT polymorphisms in any of the CKCS examined. Serum 5‐HT was associated with platelet count (P

Abstract Restoration of species‐rich grasslands is a key issue of conservation. The transfer of seed‐containing local plant material is a proven technique to restore species‐rich grassland, since it potentially allows to establish genetically variable and locally adapted populations. In our study, we tested how the transfer of local plant material affected the species diversity and composition of restored grasslands and the genetic variation of the typical grassland plant species Knautia arvensis and Plantago lanceolata. For our study, we selected fifteen study sites in southeastern Germany. We analyzed species diversity and composition and used molecular markers to investigate genetic variation within and among populations of the study species from grasslands that served as source sites for restoration and grasslands, which were restored by transfer of green hay and threshed local plant material. The results revealed no significant differences in species diversity and composition between grasslands at source and restoration sites. Levels of genetic variation within populations of the study species Knautia arvensis and Plantago lanceolata were comparable at source and restoration sites and genetic variation among populations at source and their corresponding restoration sites were only marginal different. Our study suggests that the transfer of local plant material is a restoration approach highly suited to preserve the composition of species‐rich grasslands and the natural genetic pattern of typical grassland plant species.

Abstract Background Polymorphisms of the vitamin D receptor (VDR) are associated with calcium oxalate (CaOx) nephrolithiasis in humans. Objectives To investigate the association between VDR polymorphisms and susceptibility to CaOx urolithiasis in dogs. Animals Thirty‐five dogs with CaOx urolithiasis were compared with 40 stone‐free dogs. Methods This was a case‐control study. Two VDR gene polymorphisms (rs851998024 and rs852900542) were detected by specific TaqMan real‐time polymerase chain reaction assay, and their relationship with serum 1,25‐dihydroxyvitamin D, serum and urinary electrolyte concentrations was evaluated. Results The distribution of the rs852900542 polymorphism was significantly different between the case and the control dogs (x2 = 6.369, P = .04). Dogs with a CC or CT genotype had an increased risk of CaOx stones than those with the TT genotype (odds ratio = 3.82, 95% confidence interval 1.04‐13.98). The CaOx dogs with the TT genotype had a significantly lower urinary calcium‐to‐creatinine ratio than the CT+CC genotypes. 1,25‐(OH)2D concentrations did not differ between the cases and the controls (308.7 ± 217.4 vs 286.7 ± 185.1 pg/mL, P = .45). Conclusions and Clinical Importance This finding suggests that vitamin D metabolism might play a role in CaOx stone formation in dogs.

Abstract Niche breadth, the range of environments that individuals, populations, and species can tolerate, is a fundamental ecological and evolutionary property, yet few studies have examined how niche breadth is partitioned across biological scales. We use a published dataset of thermal performance for a single population from each of 10 closely related species of western North American monkeyflowers (genus Mimulus) to investigate whether populations achieve broad thermal niches through general purpose genotypes, specialized genotypes with divergent environmental optima, and/or variation among genotypes in the degree of generalization. We found the strongest relative support for the hypothesis that populations with greater genetic variation for thermal optimum had broader thermal niches, and for every unit increase in among‐family variance in thermal optimum, population‐level thermal breadth increased by 0.508°C. While the niche breadth of a single genotype represented up to 86% of population‐level niche breadth, genotype‐level niche breadth had a weaker positive effect on population‐level breadth, with every 1°C increase in genotypic thermal breadth resulting in a 0.062°C increase in population breadth. Genetic variation for thermal breadth was not predictive of population‐level thermal breadth. These findings suggest that populations of Mimulus species have achieved broad thermal niches primarily through genotypes with divergent thermal optima and to a lesser extent via general‐purpose genotypes. Future work examining additional biological hierarchies would provide a more comprehensive understanding of how niche breadth partitioning impacts the vulnerabilities of individuals, populations, and species to environmental change.

Abstract Phenotypic variability results from interactions between genotype and environment and is a major driver of ecological and evolutionary interactions. Measuring the relative contributions of genetic variation, the environment, and their interaction to phenotypic variation remains a fundamental goal of evolutionary ecology. In this study, we assess the question: How do genetic variation and local environmental conditions interact to influence phenotype within a single population? We explored this question using seed from a single population of common milkweed, Asclepias syriaca, in northern Michigan. We first measured resistance and resistance traits of 14 maternal lines in two common garden experiments (field and greenhouse) to detect genetic variation within the population. We carried out a reciprocal transplant experiment with three of these maternal lines to assess effects of local environment on phenotype. Finally, we compared the phenotypic traits measured in our experiments with the phenotypic traits of the naturally growing maternal genets to be able to compare relative effect of genetic and environmental variation on naturally occurring phenotypic variation. We measured defoliation levels, arthropod abundances, foliar cardenolide concentrations, foliar latex exudation, foliar carbon and nitrogen concentrations, and plant growth. We found a striking lack of correlation in trait expression of the maternal lines between the common gardens, or between the common gardens and the naturally growing maternal genets, suggesting that environment plays a larger role in phenotypic trait variation of this population. We found evidence of significant genotype‐by‐environment interactions for all traits except foliar concentrations of nitrogen and cardenolide. Milkweed resistance to chewing herbivores was associated more strongly with the growing environment. We observed no variation in foliar cardenolide concentrations among maternal lines but did observe variation among maternal lines in foliar latex exudation. Overall, our data reveal powerful genotype‐by‐environment interactions on the expression of most resistance traits in milkweed.

Abstract In many cases, understanding species’ responses to climate change requires understanding variation among individuals in response to such change. For species with strong symbiotic relationships, such as many coral reef species, genetic variation in symbiont responses to temperature may affect the response to increased ocean temperatures. To assess variation among symbiont genotypes, we examined the population dynamics and physiological responses of genotypes of Breviolum antillogorgium in response to increased temperature. We found broad temperature tolerance across genotypes, with all genotypes showing positive growth at 26, 30, and 32°C. Genotypes differed in the magnitude of the response of growth rate and carrying capacity to increasing temperature, suggesting that natural selection could favor different genotypes at different temperatures. However, the historical temperature at which genotypes were reared (26 or 30°C) was not a good predictor of contemporary temperature response. We found increased photosynthetic rates and decreased respiration rates with increasing contemporary temperature, and differences in physiology among genotypes, but found no significant differences in the response of these traits to temperature among genotypes. In species with such broad thermal tolerance, selection experiments on symbionts outside of the host may not yield results sufficient for evolutionary rescue from climate change.

Abstract Climate warming alters plant composition and population dynamics of arctic ecosystems. In particular, an increase in relative abundance and cover of deciduous shrub species (shrubification) has been recorded. We inferred genetic variation of common shrub species (Alnus alnobetula, Betula nana, Salix sp.) through time. Chloroplast genomes were assembled from modern plants (n = 15) from the Siberian forest‐tundra ecotone. Sedimentary ancient DNA (sedaDNA; n = 4) was retrieved from a lake on the southern Taymyr Peninsula and analyzed by metagenomics shotgun sequencing and a hybridization capture approach. For A. alnobetula, analyses of modern DNA showed low intraspecies genetic variability and a clear geographical structure in haplotype distribution. In contrast, B. nana showed high intraspecies genetic diversity and weak geographical structure. Analyses of sedaDNA revealed a decreasing relative abundance of Alnus since 5,400 cal yr BP, whereas Betula and Salix increased. A comparison between genetic variations identified in modern DNA and sedaDNA showed that Alnus variants were maintained over the last 6,700 years in the Taymyr region. In accordance with modern individuals, the variants retrieved from Betula and Salix sedaDNA showed higher genetic diversity. The success of the hybridization capture in retrieving diverged sequences demonstrates the high potential for future studies of plant biodiversity as well as specific genetic variation on ancient DNA from lake sediments. Overall, our results suggest that shrubification has species‐specific trajectories. The low genetic diversity in A. alnobetula suggests a local population recruitment and growth response of the already present communities, whereas the higher genetic variability and lack of geographical structure in B. nana may indicate a recruitment from different populations due to more efficient seed dispersal, increasing the genetic connectivity over long distances.

Abstract Animal and plant species around the world are being challenged by the deleterious effects of inbreeding, loss of genetic diversity, and maladaptation due to widespread habitat destruction and rapid climate change. In many cases, interventions will likely be needed to safeguard populations and species and to maintain functioning ecosystems. Strategies aimed at initiating, reinstating, or enhancing patterns of gene flow via the deliberate movement of genotypes around the environment are generating growing interest with broad applications in conservation and environmental management. These diverse strategies go by various names ranging from genetic or evolutionary rescue to provenancing and genetic resurrection. Our aim here is to provide some clarification around terminology and to how these strategies are connected and linked to underlying genetic processes. We draw on case studies from the literature and outline mechanisms that underlie how the various strategies aim to increase species fitness and impact the wider community. We argue that understanding mechanisms leading to species decline and community impact is a key to successful implementation of these strategies. We emphasize the need to consider the nature of source and recipient populations, as well as associated risks and trade‐offs for the various strategies. This overview highlights where strategies are likely to have potential at population, species, and ecosystem scales, but also where they should probably not be attempted depending on the overall aims of the intervention. We advocate an approach where short‐ and long‐term strategies are integrated into a decision framework that also considers nongenetic aspects of management.

Abstract The Japanese rhinoceros beetle Trypoxylus dichotomus is one of the largest beetle species in the world and is commonly used in traditional Chinese medicine. Ten subspecies of T. dichotomus and a related Trypoxylus species (T. kanamorii) have been described throughout Asia, but their taxonomic delimitations remain problematic. To clarify issues such as taxonomy, and the degree of genetic differentiation of Trypoxylus populations, we investigated the genetic structure, genetic variability, and phylogeography of 53 specimens of Trypoxylus species from 44 locations in five Asian countries (China, Japan, Korea, Thailand, and Myanmar). Using specific‐locus amplified fragment sequencing (SLAF‐seq) techniques, we developed 330,799 SLAFs over 114.16M reads, in turn yielding 46,939 high‐resolution single nucleotide polymorphisms (SNPs) for genotyping. Phylogenetic analysis of SNPs indicated the presence of three distinct genetic groups, suggesting that the various subspecies could be treated as three groups of populations. PCA and ADMIXTURE analysis also identified three genetic clusters (North, South, West), which corresponded to their locations, suggesting that geographic factors were important in maintaining within population homogeneity and between population divergence. Analyses of SNP data confirmed the monophyly of certain subspecies on islands, while other subspecies (e.g., T. d. septentrionalis) were found to be polyphyletic and nested in more than one lineage. AMOVA demonstrated high level of differentiation among populations/groups. Also, pairwise FST values revealed high differentiation, particularly between South and West, as well as between North and South. Despite the differentiation, measurable gene flow was inferred between genetic clusters but at varying rates and directions. Our study demonstrated that SLAF‐seq derived markers outperformed 16S and COII sequences and provided improved resolution of the genetic differentiation of rhinoceros beetle populations from a large part of the species’ range.

Abstract Polyploid species possess more than two sets of chromosomes and may show high gene redundancy, hybrid vigor, and masking of deleterious alleles compared to their parent species. Following this, it is hypothesized that this makes them better at adapting to novel environments than their parent species, possibly due to phenotypic plasticity. The allopolyploid Arabidopsis suecica and its parent species A. arenosa and A. thaliana were chosen as a model system to investigate relationships between phenotypic plasticity, fitness, and genetic variation. Particularly, we test if A. suecica is more plastic, show higher genetic diversity, and/or have higher fitness than its parent species. Wild Norwegian populations of each species were analyzed for phenotypic responses to differences in availability of nutrient, water, and light, while genetic diversity was assessed through analysis of AFLP markers. Arabidopsis arenosa showed a higher level of phenotypic plasticity and higher levels of genetic diversity than the two other species, probably related to its outbreeding reproduction strategy. Furthermore, a general positive relationship between genetic diversity and phenotypic plasticity was found. Low genetic diversity was found in the inbreeding A. thaliana. Geographic spacing of populations might explain the clear genetic structure in A. arenosa, while the lack of structure in A. suecica could be due to coherent populations. Fitness measured as allocation of resources to reproduction, pointed toward A. arenosa having lower fitness under poor environmental conditions. Arabidopsis suecica, on the other hand, showed tendencies toward keeping up fitness under different environmental conditions.

Abstract The Seedlot Selection Tool and Climate‐Smart Restoration Tool are web‐based tools designed to match seedlots with planting sites assuming that seedlots are adapted to the past climates in which they evolved, primarily with respect to temperature and aridity. The tools map the climatic match of seedlots with the past or projected climates of planting sites. The challenge is that future climates are a moving target, which means that seedlots must be adapted to the near‐term climates as well as the climates of the mid‐ to late‐21st century. Because climate projections are uncertain, the prudent approach is to aim for the warmest climate that may be expected while ensuring that seedlots moved from warmer to colder locales are not moved so far that they risk cold damage. Uncertainty in climate projections may be mitigated by ensuring genetic diversity through mixing seed sources and having collections from many parents per seed source. Three examples illustrate how to effectively use the web tools: (1) choosing seedlots targeting different future climates for a mid‐elevation Douglas‐fir site in the Washington Cascades, (2) finding current and future seed sources for restoration of big sagebrush after fires in the Great Basin and Snake River Plain, and (3) planning to ensure that a Douglas‐fir seed inventory includes seedlots suitable for future climates in western Oregon and Washington.

Abstract Diet specialization may affect the population genetic structure of pollinators by reducing gene flow and driving genetic differentiation, especially in pollen‐specialist bees. Colletes gigas is a pollen‐specialist pollinator of Camellia oleifera, one of the most important staple oil crops in China. Ca. oleifera blooms in cold climates and contains special compounds that make it an unusable pollen source to other pollinators. Thus, C. gigas undoubtedly plays a key role as the main pollinator of Ca. oleifera, with biological and economic significance. Here, we use a population genomic approach to analyze the roles of geography and climate on the genetic structure, genetic diversity, and demographic history of C. gigas. A total of 1,035,407 SNPs were identified from a 582.77 Gb dataset. Clustering and phylogenetic analyses revealed a marked genetic structure, with individuals grouped into nine local clusters. A significant isolation by distance was detected by both the Mantel test (R = .866, p = .008) and linear regression (R2 = .616, p < .001). Precipitation and sunshine duration were positively and significantly (R ≥ .765, p ≤ .016) correlated with observed heterozygosity (Ho) and expected heterozygosity (He). These results showed that C. gigas populations had a distinct phylogeographic pattern determined by geographical distance and environmental factors (precipitation and sunshine duration). In addition, an analysis of paleogeographic dynamics indicated that C. gigas populations exhibited patterns of glacial expansion and interglacial contraction, likely resulting from post‐glacial habitat contraction and fragmentation. Our results indicated that the peculiar phylogeographic patterns in C. gigas populations may be related to their specialization under long‐term adaptation to host plants. This work improves our understanding of the population genetics in pollen‐specialist bees. The distinct genetic clusters identified in this study should be taken into consideration for the protection and utilization of this specialized crop pollinator.

Abstract Genetic diversity is important for long‐term viability of a population. Low genetic diversity reduces persistence and survival of populations and increases susceptibility to diseases. Comparisons of the neutral markers with functional loci such as immune genes [Toll‐like receptors; TLR] can provide useful insights into evolutionary potential of a species and how the diversity of pathogens and selection pressures on their hosts are directly linked to their environment. In this study, we compare genetic diversity in neutral (eleven microsatellite loci) and adaptive (seven TLR loci) loci to determine genetic variation in a nonmigratory western Himalayan passerine, the black‐throated tit (Aegithalos concinnus), distributed across an elevation gradient with varying degree of pathogen‐mediated selection pressure. We further compare the diversity in TLR loci with a high‐elevation sister species, the white‐throated tit (Aegithalos niveogularis). Our results indicate a lack of population genetic structure in the black‐throated tit and signatures of a past bottleneck. In contrast, we found high diversity in TLR loci and locus‐specific (TLR7) signatures of pathogen‐mediated selection, which was comparable to diversity in the white‐throated tit. Levels of diversity at TLR5 locus corresponded very closely with neutral microsatellite variation. We found evidence of positive selection in TLR1LA, TLR5, and TLR7 loci highlighting the importance in pathogen recognition. Our finding demonstrates that reduction in neutral variation does not necessarily lead to reduction in functional genetic diversity and probably helps in revival of population in a widespread species.

Abstract The three mussel species comprising the Mytilus complex are widespread across Europe and readily hybridize when they occur in sympatry, resulting in a mosaic of populations with varying genomic backgrounds. Two of these species, M. edulis and M. galloprovincialis, are extensively cultivated across Europe, with annual production exceeding 230,000 tonnes. The third species, M. trossulus, is considered commercially damaging as hybridization with this species results in weaker shells and poor meat quality. We therefore used restriction site associated DNA sequencing to generate high‐resolution insights into the structure of the Mytilus complex across Europe and to resolve patterns of introgression. Inferred species distributions were concordant with the results of previous studies based on smaller numbers of genetic markers, with M. edulis and M. galloprovincialis predominating in northern and southern Europe respectively, while introgression between these species was most pronounced in northern France and the Shetland Islands. We also detected traces of M. trossulus ancestry in several northern European populations, especially around the Baltic and in northern Scotland. Finally, genome‐wide heterozygosity, whether quantified at the population or individual level, was lowest in M. edulis, intermediate in M. galloprovincialis, and highest in M. trossulus, while introgression was positively associated with heterozygosity in M. edulis but negatively associated with heterozygosity in M. galloprovincialis. Our study will help to inform mussel aquaculture by providing baseline information on the genomic backgrounds of different Mytilus populations across Europe and by elucidating the effects of introgression on genome‐wide heterozygosity, which is known to influence commercially important traits such as growth, viability, and fecundity in mussels.

Abstract Positive selection may be the main factor of the between‐population divergence in gene expression. Expression profiles of two Drosophila melanogaster laboratory strains of different geographical origin and long‐term laboratory maintenance were analyzed using microchip arrays encompassing probes for 18,500 transcripts. The Russian strain D18 and the North American strain Canton‐S were compared. A set of 223 known or putative genes demonstrated significant changes in expression levels between these strains. Differentially expressed genes (DEG) were enriched in response to DDT (p = .0014), proteolysis (p = 2.285E−5), transmembrane transport (p = 1.03E−4), carbohydrate metabolic process (p = .0317), protein homotetramerization (p = .0444), and antibacterial humoral response (p = 425E−4). The expression in subset of genes from different categories was verified by qRT‐PCR. Analysis of transcript abundance between Canton‐S and D18 strains allowed to select several genes to estimate their participation in latitude adaptation. Expression of selected genes was analyzed in five D. melanogaster lines of different geographic origins by qRT‐PCR, and we found two candidate genes that may be associated with latitude adaptation in adult flies—smp‐30 and Cda9. Quite possible that several alleles of these genes may be important for insect survival in the environments of global warming. It is interesting that the number of genes involved in local adaptation demonstrates expression level appropriate to their geographical origin even after decades of laboratory maintenance.

Abstract The Mexican highlands are areas of high biological complexity where taxa of Nearctic and Neotropical origin and different population histories are found. To gain a more detailed view of the evolution of the biota in these regions, it is necessary to evaluate the effects of historical tectonic and climate events on species. Here, we analyzed the phylogeographic structure, historical demographic processes, and the contemporary period, Last Glacial Maximum (LGM) and Last Interglacial (LIG) ecological niche models of Quercus castanea, to infer the historical population dynamics of this oak distributed in the Mexican highlands. A total of 36 populations of Q. castanea were genotyped with seven chloroplast microsatellite loci in four recognized biogeographic provinces of Mexico: the Sierra Madre Occidental (western mountain range), the Central Plateau, the Trans‐Mexican Volcanic Belt (TMVB, mountain range crossing central Mexico from west to east) and the Sierra Madre del Sur (SMS, southern mountain range). We obtained standard statistics of genetic diversity and structure and tested for signals of historical demographic expansions. A total of 90 haplotypes were identified, and 29 of these haplotypes were restricted to single populations. The within‐population genetic diversity was high (mean hS = 0.72), and among‐population genetic differentiation showed a strong phylogeographic structure (NST = 0.630 > GST = 0.266; p

Abstract Transposable elements are abundant, dynamic components of the genome that affect organismal phenotypes and fitness. In Drosophila melanogaster, they have increased in abundance as the species spread out of Africa, and different populations differ in their transposable element content. However, very little is currently known about how transposable elements differ between individual genotypes, and how that relates to the population dynamics of transposable elements overall. The sister species of D. melanogaster, D. simulans, has also recently become cosmopolitan, and panels of inbred genotypes exist from cosmopolitan and African flies. Therefore, we can determine whether the differences in colonizing populations are repeated in D. simulans, what the dynamics of transposable elements are in individual genotypes, and how that compares to wild flies. After estimating copy number in cosmopolitan and African D. simulans, I find that transposable element load is higher in flies from cosmopolitan populations. In addition, transposable element load varies considerably between populations, between genotypes, but not overall between wild and inbred lines. Certain genotypes either contain active transposable elements or are more permissive of transposition and accumulate copies of particular transposable elements. Overall, it is important to quantify genotype‐specific transposable element dynamics as well as population averages to understand the dynamics of transposable element accumulation over time.

Abstract Population restoration is an inherently costly conservation practice typically reliant on animal translocations. There are many approaches to translocation and consideration is paid to understanding how various translocation models influence restoration success. Translocation strategies are often designed to meet site‐specific objectives, minimize cost, and maximize success. We investigated genetic diversity retention associated with the low‐founder, multi‐release, single admixed stock translocation model of the Missouri elk (Cervus canadensis) restoration in 2011–2013. We further estimated effective population size and projected future losses in genetic diversity if the restored Missouri elk herd is maintained at the population size objective with no immigration from neighboring states. We observed relatively high levels of genetic diversity retention as evidenced by minimal losses in allelic richness and expected heterozygosity. Our projections indicated 90% genetic diversity retention within the Missouri population for roughly 130 years. Where number of progeny or source stocks are limited by resource or disease considerations, use of a relatively low‐founder, single admixed source may enable retention of genetic variation, while minimizing costs.

Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. Physiologically-based PK (PBPK) models are an attractive alternative that can account for physiologic-, genetic-, and drug-specific changes without the need for extensive clinical trial data. In this study, we explored the effect of obesity on pantoprazole PK and evaluated label-suggested dosing in this population. An adult PBPK model for pantoprazole was developed using data from the literature and accounting for genetic variation in CYP2C19. The adult PBPK model was scaled to children without obesity using age-associated changes in anatomical and physiological parameters. Lastly, the pediatric PBPK model was expanded to children with obesity. Three pantoprazole dosing strategies were evaluated: 1 mg/kg total body weight, 1.2 mg/kg lean body weight, and US Food and Drug Administration-recommended weight-tiered dosing. Simulated concentration-time profiles from our model were compared with data from a prospective cohort study (PAN01; NCT02186652). Weight-tiered dosing resulted in the most (>90%) children with pantoprazole exposures in the reference range, regardless of obesity status or CYP2C19 phenotype, confirming results from previously published population PK models. PBPK models may allow for the efficient study of physiologic and developmental effects of obesity on PK in special populations where clinical trial data may be limited., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Premise: Evolution of cross-pollination efficiency depends on the genetic variation of flower traits, the pollen vector, and flower trait matching between pollen donors and recipients. Trait matching has been almost unexplored among nonheterostylous species, and we examined whether the match of anther length in pollen donors and stigma length in pollen recipients influences the efficiency of cross-pollination. To explore potential constraints for evolutionary response, we also quantified genetic variation and covariation among sepal length, petal length and width, stamen length, style length, and herkogamy., Methods: We created 58 experimental arrays of Turnera velutina that varied in the extent of mismatch in the position of anthers and stigmas between single-flowered plants. Genetic variation and correlations among flower traits were estimated under greenhouse conditions., Results: Style length, but not herkogamy, influenced the efficiency of cross-pollination. Plants with stamen length that matched the style length of other plants were more efficient pollen donors, whereas those with the style protruding above the stamens of other plants were more efficient pollen recipients. Significant broad-sense heritability (0.22 > h B 2  < 0.42) and moderate genetic correlations (0.33 > r < 0.85) among floral traits were detected., Conclusions: Our results demonstrated that anther-stigma mismatch between flowers contributed to variation in the efficiency of cross-pollination. The genetic correlations between stamen length and other floral traits suggests that any change in cross-pollination efficiency would be driven by changes in style rather than in stamen length., (© 2024 The Author(s). American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

T cells express a T-cell receptor (TCR) heterodimer that is the product of germline rearrangement and junctional editing resulting in immense clonotypic diversity. The generation of diverse TCR repertoires enables the recognition of pathogen-derived peptide antigens presented by polymorphic major histocompatibility complex (MHC) molecules. However, T cells also recognize nonpeptide antigens through nearly monomorphic antigen-presenting systems, such as cluster of differentiation 1 (CD1), MHC-related protein 1 (MR1) and butyrophilins (BTNs). This potential for shared immune responses across genetically diverse populations led to their designation as donor-unrestricted T cells (DURTs). As might be expected, some CD1-, MR1- and BTN-restricted T cells express a TCR that is conserved across unrelated individuals. However, several recent studies have reported unexpected diversity among DURT TCRs, and increasing evidence suggests that this diversity has functional consequences. Recent reports also challenge the dogma that immune cells are either innate or adaptive and suggest that DURT TCRs may act in both capacities. Here, we review this evidence and propose an expanded view of the role for clonotypic diversity among DURTs in humans, including new perspectives on how DURT TCRs may integrate their adaptive and innate immune functions., (© 2024 the Australian and New Zealand Society for Immunology, Inc.)

Premise: The domestication of wild plant species can begin with gathering and transport of propagules by Indigenous peoples. The effect on genomic composition, especially in clonal, self-incompatible perennials would be instantaneous and drastic with respect to new, anthropogenic populations subsequently established. Reductions in genetic diversity and mating capability would be symptomatic and the presence of unique alleles and genetic sequences would reveal the origins and ancestry of populations associated with archaeological sites. The current distribution of the Four Corners potato, Solanum jamesii Torr. in the Southwestern USA, may thus reflect the early stages of a domestication process that began with tuber transport., Methods: Herein genetic sequencing (GBS) data are used to further examine the hypothesis of domestication in this culturally significant species by sampling 25 archaeological and non-archaeological populations., Results: Archaeological populations from Utah, Colorado and northern Arizona have lower levels of polymorphic loci, unique alleles, and heterozygosity than non-archaeological populations from the Mogollon region of central Arizona and New Mexico. Principle components analysis, Fst values, and structure analysis revealed that genetic relationships among archaeological populations did not correspond to geographic proximity. Populations in Escalante, Utah were related to those on the Mogollon Rim (400 km south) and had multiple origins and significant disjunctions with those populations in Bears Ears, Chaco Canyon, and Mesa Verde sites., Conclusions: Movement of tubers from the Mogollon region may have occurred many times and in multiple directions during the past, resulting in the complex genetic patterns seen in populations from across the Four Corners region., (© 2024 The Author(s). American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Premise: Light is essential for plants, and local populations exhibit adaptive photosynthetic traits depending on their habitats. Although plastic responses in morphological and/or physiological characteristics to different light intensities are well known, adaptive divergence with genetic variation remains to be explored. This study focused on Saxifraga fortunei (Saxifragaceae) growing in sun-exposed and shaded habitats., Methods: We measured the leaf anatomical structure and photosynthetic rate of plants grown in their natural habitats and in a common greenhouse (high- and low-intensity light experimental sites). To assess differences in ecophysiological tolerance to high-intensity light between the sun and shade types, we evaluated the level of photoinhibition of photosystem II and the leaf mortality rate under high-intensity light conditions. In addition, population genetic analysis was conducted to investigate phylogenetic origins., Results: Clear phenotypic differences were found between the sun and shade types despite their recent phylogenetic origin. The leaf anatomical structure and photosynthetic rate showed plastic changes in response to growing conditions. Moreover, the sun type had a well-developed palisade parenchyma and a higher photosynthetic rate, which were genetically fixed, and a lower level of photoinhibition under high-intensity light., Conclusions: Our findings demonstrate that light intensity is a selective pressure that can rapidly promote phenotypic divergence between the sun and shade types. While phenotypic changes in multiple photosynthetic traits were plastic, genetic divergence in specific traits related to adaptation to high-intensity light would be fundamental for ecotypic divergence to different light regimes., (© 2024 Botanical Society of America.)

Premise: Bracken (Pteridium, Dennstaedtiaceae) is a cosmopolitan genus of aggressive disturbance colonizers that are toxic to agricultural livestock. The taxonomy of Pteridium has been treated in multiple schemes, ranging from one to six species worldwide, with numerous subspecies and varieties. Recent work has focused on the worldwide distribution and systematics of the bracken fern, but South America has been poorly represented. We present the first continent-wide sampling and analysis of Pteridium esculentum, a Southern Hemisphere diploid species., Methods: Within South America, P. esculentum has several morphotypes, distinguished into subspecies by variation in indument and lamina architecture. We used double digest restriction site-associated DNA sequencing (ddRADSeq) to assess the phylogenetic relationships of P. esculentum subspecies., Results: We found a striking genetic homogeneity in the species, being able to support only two morphotypes from molecular data: P. e. arachnoideum and P. e. campestre. We had high confidence for shallow and deep phylogenetic relationships, but less support for relationships among crown groups., Conclusions: We describe an east-west geographic pattern that would explain the relationships between populations; and, in contrast to previous studies, we detected differences with P. esculentum from Australia. These results will lay the foundations for studying variations in this species' behavior as a weed, as well as its impact on the production of agricultural livestock in South America., (© 2024 Botanical Society of America.)

Fabry disease (FD) is an X-linked multiorgan disorder caused by variants in the alpha-galactosidase A gene (GLA). Depending on the variant, disease phenotypes range from benign to life-threatening. More than 1000 GLA variants are known, but a link between genotype and phenotype in FD has not yet been established for all. p.A143T, p.D313Y, and p.S126G are frequent examples of variants of unknown significance (VUS). We have investigated the potential pathogenicity of these VUS combining clinical data with data obtained in human cellular in vitro systems. We have analyzed four different male subject-derived cell types for alpha-galactosidase A enzyme (GLA) activity and intracellular Gb3 load. Additionally, Gb3 load in skin tissue as well as clinical data were studied for correlates of disease manifestations. A reduction of GLA activity was observed in cells carrying p.A143T compared with controls (p < 0.05). In cells carrying the p.D313Y variant, a reduced GLA activity was found only in endothelial cells (p < 0.01) compared with controls. No pathological changes were observed in cells carrying the p.S126G variant. None of the VUS investigated caused intracellular Gb3 accumulation in any cell type. Our data of aberrant GLA activity in cells of p.A143T hemizygotes and overall normal cellular phenotypes in cells of p.D313Y and p.S126G hemizygotes contribute a basic science perspective to the clinically highly relevant discussion on VUS in GLA., (© 2024 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Massive genetic compendiums such as the UK Biobank have become an invaluable resource for identifying genetic variants that are associated with complex diseases. Due to the difficulties of massive data collection, a common practice of these compendiums is to collect interval-censored data. One challenge in analyzing such data is the lack of methodology available for genetic association studies with interval-censored data. Genetic effects are difficult to detect because of their rare and weak nature, and often the time-to-event outcomes are transformed to binary phenotypes for access to more powerful signal detection approaches. However transforming the data to binary outcomes can result in loss of valuable information. To alleviate such challenges, this work develops methodology to associate genetic variant sets with multiple interval-censored outcomes. Testing sets of variants such as genes or pathways is a common approach in genetic association settings to lower the multiple testing burden, aggregate small effects, and improve interpretations of results. Instead of performing inference with only a single outcome, utilizing multiple outcomes can increase statistical power by aggregating information across multiple correlated phenotypes. Simulations show that the proposed strategy can offer significant power gains over a single outcome approach. We apply the proposed test to the investigation that motivated this study, a search for the genes that perturb risks of bone fractures and falls in the UK Biobank., (© 2024 John Wiley & Sons Ltd.)