Warmer is better for evolutionary rescue, driving a warm-to-cold bias in habitat colonization dynamics.

Evolutionary rescue occurs when populations survive lethal environmental stresses through the rising and fixation of tolerant genotypes. Temperature has long been believed to determine the evolutionary speed of populations and species. Here, we suggest that warmer temperatures can facilitate evolutionary rescue. Moreover, with dispersal among habitats, the advantage in evolutionary rescue for warmer populations may cause a bias in habitat colonization dynamics towards the warm-to-cold direction. We experimentally tested these hypotheses with a model microbial system. Our first experiment showed that bacterial populations at warmer temperatures had a greater chance to evolve resistance and escape the fate of extinction under an antibiotic treatment. In the second experiment, metapopulations that consisted of warm and cold habitats were exposed to the antibiotic stress; local populations that went extinct might be recolonized, and such recolonization events were biased to the warm-to-cold direction. We also examined possible mechanisms underlying the temperature effect on the rapid evolution of resistance in our study system. Our results may help to understand the mechanisms of maintenance of biodiversity and patterns of gene flow among climatic regions, particularly in pest species subject to chemical control treatments.

Genetic Variants ε2 and ε4 of APOE Predict Mortality and Poor Outcome Independently in Spontaneous Intracerebral Hemorrhage Within the Chinese Han Population.

The heightened mortality and disability rates, coupled with restricted neurological recovery post intracerebral hemorrhage (ICH), have sparked considerable attention toward its treatment and results. Simultaneously, the influence of the APOE gene on ICH prognosis has been well-documented. This research aimed to explore the relationship between specific APOE alleles in the present cohort and the incidences of mortality, recurrence, and adverse prognosis, as determined by neurological function assessments in ICH patients. Data on patients diagnosed with ICH and hospitalized in the Department of Neurology at our institution from October 2021 to March 2022 were collected, including determining their APOE genotypes. A 1-year follow-up was conducted to evaluate mortality, ICH recurrence, and modified Rankin Scale (mRS) scores at 3 and 12 months. Poor prognosis was defined as an mRS score of ≥ 3. Initially, we analyzed the relationships between different APOE alleles and mortality, recurrence, and poor prognosis. Subsequently, we explored additional factors influencing each prognostic outcome and conducted multivariate analysis to identify independent risk factors. An analysis was conducted on 289 patients diagnosed with ICH. The presence of the ε2 allele was found to be a significant independent predictor for unfavorable outcomes at both 3 months (p = 0.022, OR = 2.138, 95% CI [2.041, 3.470]) and 1 year (p = 0.020, OR = 5.116, 95% CI [5.044, 5.307]). Moreover, the ε4 allele was established as an independent risk factor for ICH recurrence within 1 year (p = 0.025, OR = 2.326, 95% CI [1.163, 2.652]), as well as for mortality at 3 months (p = 0.037, OR = 4.250, 95% CI [4.068, 4.920]) and 1 year (p = 0.023, OR = 4.109, 95% CI [4.016, 4.739]). In conclusions, Both APOE ε2 and ε4 variants independently heighten mortality risk, recurrence, and poor prognosis after ICH. The substantial influence underscores the need for additional investigation into the impact of APOE genotype on ICH prognosis.

Novel variants and genotype-phenotype correlation in a multicentre cohort of GNE myopathy in China.

BACKGROUND: GlcNAc2-epimerase (GNE) myopathy is a rare autosomal recessive disorder caused by pathogenic variants in the GNE gene, which is essential for the sialic acid biosynthesis pathway. OBJECTIVE: This multi-centre study aimed to delineate the clinical phenotype and GNE variant spectrum in Chinese patients, enhancing our understanding of the genetic diversity and clinical manifestation across different populations. METHODS: We retrospectively analysed GNE variants from 113 patients, integrating these data with external GNE variants from online databases for a global perspective, examining their consequences, distribution, ethnicity and severity. RESULTS: This study revealed 97 distinct GNE variants, including 35 (36.08%) novel variants. Two more patients with deep intronic variant c.862+870C>T were identified, while whole genome sequencing (WGS) uncovered another two novel intronic variants: c.52-8924G>T and c.1505-12G>A. Nanopore long reads sequencing (LRS) and further PCR analysis verified a 639 bp insertion at chr9:36249241. Missense variants predominantly located in the epimerase/kinase domain coding region, indicating the impairment of catalytic function as a key pathogenic consequence. Comparative studies with Japanese, Korean and Jewish, our cohorts showed later onset ages by 2 years. The high allele frequency of the non-catalytic GNE variant, c.620A>T, might underlie the milder phenotype of Chinese patients. CONCLUSIONS: Comprehensive techniques such as WGS and Nanopore LRS warrants the identifying of GNE variants. Patients with the non-catalytic GNE variant, c.620A>T, had a milder disease progression and later wheelchair use.

Analysis of CNS autoimmunity in genetically diverse mice reveals unique phenotypes and mechanisms.

Multiple sclerosis (MS) is a complex disease with significant heterogeneity in disease course and progression. Genetic studies have identified numerous loci associated with MS risk, but the genetic basis of disease progression remains elusive. To address this, we leveraged the Collaborative Cross (CC), a genetically diverse mouse strain panel, and experimental autoimmune encephalomyelitis (EAE). The thirty-two CC strains studied captured a wide spectrum of EAE severity, trajectory, and presentation, including severe-progressive, monophasic, relapsing remitting, and axial rotary (AR)-EAE, accompanied by distinct immunopathology. Sex differences in EAE severity were observed in six strains. Quantitative trait locus analysis revealed distinct genetic linkage patterns for different EAE phenotypes, including EAE severity and incidence of AR-EAE. Machine learning-based approaches prioritized candidate genes for loci underlying EAE severity (Abcc4 and Gpc6) and AR-EAE (Yap1 and Dync2h1). This work expands the EAE phenotypic repertoire and identifies novel loci controlling unique EAE phenotypes, supporting the hypothesis that heterogeneity in MS disease course is driven by genetic variation.

Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis.

OBJECTIVES: Pseudomonas aeruginosa is the most common pathogen in the bronchiectasis lung, associated with worsened outcomes. P. aeruginosa genomic studies in this context have been limited to single-country, European studies. We aimed to determine strain diversity, adaptation mechanisms, and AMR features to better inform treatment. METHODS: P. aeruginosa from 180 bronchiectasis patients in 15 countries, obtained prior to a phase 3, randomised clinical trial (ORBIT-3), were analysed by whole-genome sequencing. Phylogenetic groups and sequence types were determined, and between versus within patient genetic diversity compared using Analysis of Molecular Variance (AMOVA). The frequency of AMR-associated genes and mutations was also determined. RESULTS: A total of 2854 P. aeruginosa isolates were analysed, predominantly belonging to phylogenetic group 1 (83%, n = 2359). Genetic diversity was far greater between than within patients, responsible for >99.9% of total diversity (AMOVA: phylogroup 1: df = 145, P < 0.01). Numerous pathways were under selection, some shared with CF (e.g., motility, iron acquisition), some unique to bronchiectasis (e.g., novel efflux pump PA1874). Multidrug resistance features were also frequent. CONCLUSIONS: We present a 10-fold increase in the availability of genomic data for P. aeruginosa in bronchiectasis, highlighting key distinctions with cystic fibrosis and potential targets for future treatments.

A 10-Year Review on Advancements in Identifying and Treating Intellectual Disability Caused by Genetic Variations.

Intellectual disability (ID) is a prevalent neurodevelopmental disorder characterized by neurodevelopmental defects such as the congenital impairment of intellectual function and restricted adaptive behavior. However, genetic studies have been significantly hindered by the extreme clinical and genetic heterogeneity of the subjects under investigation. With the development of gene sequencing technologies, more genetic variations have been discovered, assisting efforts in ID identification and treatment. In this review, the physiological basis of gene variations in ID is systematically explained, the diagnosis and therapy of ID is comprehensively described, and the potential of genetic therapies and exercise therapy in the rehabilitation of individuals with intellectual disabilities are highlighted, offering new perspectives for treatment approaches.

Candidate Genes Associated with Survival Following Highly Pathogenic Avian Influenza Infection in Chickens.

Highly pathogenic strains of avian influenza (HPAI) devastate poultry flocks and result in significant economic losses for farmers due to high mortality, reduced egg production, and mandated euthanization of infected flocks. Within recent years, HPAI outbreaks have affected egg production flocks across the world. The H5N2 outbreak in the US in 2015 resulted in over 99% mortality. Here, we analyze sequence data from chickens that survived (42 cases) along with uninfected controls (28 samples) to find genomic regions that differ between these two groups and that, therefore, may encompass prime candidates that are resistant to HPAI. Blood samples were obtained from survivors of the 2015 HPAI outbreak plus age and genetics-matched non-affected controls. A whole-genome sequence was obtained, and genetic variants were characterized and used in a genome-wide association study to identify regions showing significant association with survival. Regions associated with HPAI resistance were observed on chromosomes 1, 2, 5, 8, 10, 11, 15, 20, and 28, with a number of candidate genes identified. We did not detect a specific locus which could fully explain the difference between survivors and controls. Influenza virus replication depends on multiple components of the host cellular machinery, with many genes involved in the host response.

The implication of ADRA2A and AVPRIB gene variants in the aetiology of stress-related bipolar disorder.

OBJECTIVE: Bipolar disorder is a complex and severe mental illness characterised by manic and depressive episodes that can be triggered and exacerbated by psychosocial, environmental, and biological stressors. Genetic variations are a risk factor for bipolar disorder. However, the identification of the exact gene variants and genotypes remains complex. This study, therefore, aims to identify the potential association between genotypes of analysed single nucleotide polymorphisms and the presence of a stressor in bipolar disorder patients. METHOD: We analysed 114 single nucleotide polymorphisms (SNPs) from bipolar and stress-related candidate genes in 550 patients with bipolar disorders (60.36 % females and 39.64 % male). We compared SNPs of patients reporting the presence (40.73 %) or absence of stressors (59.27 %) before the first episode using the Persons Chi-square test and Bayes Factor t-test. The genotyping of 114 SNPs was done using TaqMan assays. Statistical analysis was done using Statistica 13.3 software (StatSoft Poland, Krakow, Poland), R programming, and G*Power statistics. RESULT: We found significant differences in genotype distribution (p < 0.05) in 6 polymorphisms (AVPRIB/rs28536160, FKBP4/rs2968909, ADRA2A/rs3750625, 5HTR2A/rs6311, 5HTR2A/rs6313, and GLCCI1/rs37972) when comparing BD patient with and without stressor with a small effect of d = 0.2. Of these, two gene variants (ADRA2A/rs3750625/AC and AVPRIB/rs28536160/CT) with minor alleles formed an association with the presence of a stressor prior to the disease onset and favoured the alternative hypothesis using Bayes Factor Analysis t-test for hypothesis testing. CONCLUSION: This study presents a novel association of ADRA2A/rs3750625/AC and AVPR1B/rs28536160/CT gene variants in stress-related bipolar disorder with the AC genotype of ADRA2A/rs3750625 constituting a risk genotype and CT of AVPR1B/rs28536160 constituting a protective genotype. However, further functional analysis is required to fully understand their clinical and biological significance and interaction.

Genetics causal analysis of oral microbiome on type 2 diabetes in East Asian populations: a bidirectional two-sample Mendelian randomized study.

Introduction: The dysbiosis of the oral microbiome is associated with the progression of various systemic diseases, including diabetes. However, the precise causal relationships remain elusive. This study aims to investigate the potential causal associations between oral microbiome and type 2 diabetes (T2D) using Mendelian randomization (MR) analyses. Methods: We conducted bidirectional two-sample MR analyses to investigate the impact of oral microbiome from saliva and the tongue T2D. This analysis was based on metagenome-genome-wide association studies (mgGWAS) summary statistics of the oral microbiome and a large meta-analysis of GWAS of T2D in East Asian populations. Additionally, we utilized the T2D GWAS summary statistics from the Biobank Japan (BBJ) project for replication. The MR methods employed included Wald ratio, inverse variance weighting (IVW), weighted median, MR-Egger, contamination mixture (ConMix), and robust adjusted profile score (RAPS). Results: Our MR analyses revealed genetic associations between specific bacterial species in the oral microbiome of saliva and tongue with T2D in East Asian populations. The MR results indicated that nine genera were shared by both saliva and tongue. Among these, the genera Aggregatibacter, Pauljensenia, and Prevotella were identified as risk factors for T2D. Conversely, the genera Granulicatella and Haemophilus D were found to be protective elements against T2D. However, different species within the genera Catonella, Lachnoanaerobaculum, Streptococcus, and Saccharimonadaceae TM7x exhibited multifaceted influences; some species were positively correlated with the risk of developing T2D, while others were negatively correlated. Discussion: This study utilized genetic variation tools to confirm the causal effect of specific oral microbiomes on T2D in East Asian populations. These findings provide valuable insights for the treatment and early screening of T2D, potentially informing more targeted and effective therapeutic strategies.

Reprint: Acclimatization and Adaptive Capacity of Marine Species in a Changing Ocean.

To persist in an ocean changing in temperature, pH and other stressors related to climate change, many marine species will likely need to acclimatize or adapt to avoid extinction. If marine populations possess adequate genetic variation in tolerance to climate change stressors, species might be able to adapt to environmental change. Marine climate change research is moving away from single life stage studies where individuals are directly placed into projected scenarios ('future shock' approach), to focus on the adaptive potential of populations in an ocean that will gradually change over coming decades. This review summarizes studies that consider the adaptive potential of marine invertebrates to climate change stressors and the methods that have been applied to this research, including quantitative genetics, laboratory selection studies and trans- and multigenerational experiments. Phenotypic plasticity is likely to contribute to population persistence providing time for genetic adaptation to occur. Transgenerational and epigenetic effects indicate that the environmental and physiological history of the parents can affect offspring performance. There is a need for long-term, multigenerational experiments to determine the influence of phenotypic plasticity, genetic variation and transgenerational effects on species' capacity to persist in a changing ocean. However, multigenerational studies are only practicable for short generation species. Consideration of multiple morphological and physiological traits, including changes in molecular processes (eg, DNA methylation) and long-term studies that facilitate acclimatization will be essential in making informed predictions of how the seascape and marine communities will be altered by climate change.

Electronic health record biobank cohort recapitulates an association between the MUC5B promoter polymorphism and ARDS in critically ill adults.

Background: Large population-based DNA biobanks linked to electronic health records (EHRs) may provide advantages over traditional study designs for identifying genetic drivers of ARDS. Research Question: Can ARDS be identified in an EHR biobank, and can this approach validate a previously reported genetic risk factor for ARDS? Study Design and Methods: We analyzed two genotyped cohorts from one academic medical center: a prospective biomarker study of critically ill adults (VALID cohort), and hospitalized participants in a de-identified EHR biobank (BioVU). ARDS status was assessed by clinician-investigator review in VALID and an EHR-derived algorithm in BioVU (EHR-ARDS). We tested the association between the MUC5B promoter polymorphism (rs35705950) with development of ARDS/EHR-ARDS in each cohort. Results: In VALID, 2,795 patients were included, age was 55 [43, 66] (median [IQR]) years, and 718 (25.7%) developed ARDS. In BioVU, 9,025 hospitalized participants were included, age was 60 [48, 70] , and 1,056 (11.7%) developed EHR-ARDS. We observed a significant interaction between age and rs35705950 on ARDS risk in VALID: in older patients rs35705950 was associated with increased ARDS risk (OR: 1.44; 95%CI 1.08-1.92; p=0.012) whereas among younger patients this effect was attenuated (OR: 0.84; 95%CI: 0.62-1.14; p=0.26). In BioVU, rs35705950 was associated with increased risk for EHR-ARDS among all participants (OR: 1.20; 95%CI: 1.00-1.43, p=0.043) and this relationship did not vary by age. The polymorphism was also associated with more severe oxygenation impairment among BioVU participants who required mechanical ventilation. Interpretation: The MUC5B promoter polymorphism was associated with ARDS in two cohorts of at-risk hospitalized adults. Although age-related effect modification was observed only in the prospective biomarker cohort, the EHR cohort identified a consistent association between MUC5B and ARDS risk regardless of age and a novel association with oxygenation impairment. Our study highlights the potential for EHR biobanks to enable precision-medicine ARDS studies.

Effect of Chromosomal Localization of NGS-Based Markers on Their Applicability for Analyzing Genetic Variation and Population Structure of Hexaploid Triticale.

This study aimed to determine whether using DNA-based markers assigned to individual chromosomes would detect the genetic structures of 446 winter triticale forms originating from two breeding companies more effectively than using the entire pool of markers. After filtering for quality control parameters, 6380 codominant single nucleotide polymorphisms (SNPs) markers and 17,490 dominant diversity array technology (silicoDArT) markers were considered for analysis. The mean polymorphic information content (PIC) values varied depending on the chromosomes and ranged from 0.30 (2R) to 0.43 (7A) for the SNPs and from 0.28 (2A) to 0.35 (6R) for the silicoDArTs. The highest correlation of genetic distance (GD) matrices based on SNP markers was observed among the 5B-5R (0.642), 5B-7B (0.626), and 5A-5R (0.605) chromosomes. When silicoDArTs were used for the analysis, the strongest correlations were found between 5B-5R (0.732) and 2B-5B (0.718). A Bayesian analysis showed that SNPs (total marker pool) allowed for the identification of a more complex structure (K = 4, ΔK = 2460.2) than the analysis based on silicoDArTs (K = 2, ΔK = 128). Triticale lines formed into groups, ranging from two (most of the chromosomes) to four (7A) groups depending on the analyzed chromosome when SNP markers were used for analysis. Linkage disequilibrium (LD) varied among individual chromosomes, ranging from 0.031 for 1A to 0.228 for 7R.

Genetic and phenotypic evidence suggest the existence of indigenous olive population of wild var. sylvestris in the Carmel coast, southern Levant.

BACKGROUND: Populations of Olea europaea subsp. europaea var. sylvestris, the ancestor of cultivated olives, are scattered across the Mediterranean Basin. However, after millennia of possible hybridization with cultivated varieties, the genetic identity of many of these populations remain questionable. In the southern Levant, the plausible primary domestication center of olives, many of the naturally growing olive (NGOs) are considered feral, having developed from nearby olive groves. Here, we investigated the genetic identity of NGOs population in the Carmel region, hypothesizing that their specific location, which limit anemophily, provided an opportunity for the persistence of genuine var. sylvestris. RESULTS: We mapped more than 1,000 NGOs on the Kurkar ridge along the Carmel coast, within and outside the residential area of Atlit and used simple sequence repeats of 14 loci to assess the spatial genetic structure of 129 NGOs. Genetic diversity parameters and genetic distances between NGO and cultivated olives, as well as phenotypic and morphometric analyses of their oil content and pits, respectively, indicated the presence of a genuine var. sylvestris population. However, NGOs within the residential area of Atlit and old settlements showed an intermediate admix genetic structure, indicating on hybridization with local varieties, a consequence of their proximity to cultivated trees. CONCLUSIONS: Integrating the results of genetic and phenotypic analyses we provide crucial evidence of the presence of a genuine var. sylvestris population in the southern Levant, in close geographical proximity to archaeological sites with the earliest evidence of olive exploitation in the ancient world. We supplement the results with recommendations for a conservation program that combines municipal requirements and the urgent need to preserve the largest population of var. sylvestris in the southern Levant.

The PS4-likelihood ratio calculator: flexible allocation of evidence weighting for case-control data in variant classification.

BACKGROUND: The 2015 American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant classification framework specifies that case-control observations can be scored as 'strong' evidence (PS4) towards pathogenicity. METHODS: We developed the PS4-likelihood ratio calculator (PS4-LRCalc) for quantitative evidence assignment based on the observed variant frequencies in cases and controls. Binomial likelihoods are computed for two models, each defined by prespecified OR thresholds. Model 1 represents the hypothesis of association between variant and phenotype (eg, OR≥5) and model 2 represents the hypothesis of non-association (eg, OR≤1). RESULTS: PS4-LRCalc enables continuous quantitation of evidence for variant classification expressed as a likelihood ratio (LR), which can be log-converted into log LR (evidence points). Using PS4-LRCalc, observed data can be used to quantify evidence towards either pathogenicity or benignity. Variants can also be evaluated against models of different penetrance. The approach is applicable to balanced data sets generated for more common phenotypes and smaller data sets more typical in very rare disease variant evaluation. CONCLUSION: PS4-LRCalc enables flexible evidence quantitation on a continuous scale for observed case-control data. The converted LR is amenable to incorporation into the now widely used 2018 updated Bayesian ACMG/AMP framework.

Genetic variation and recombination analysis of PRRSV-2 GP3 gene in China from 1996 to 2023.

Porcine reproductive and respiratory syndrome virus (PRRSV) has become widespread in China particularly the highly pathogenic porcine reproductive and respiratory syndromes (HP-PRRSV), NADC30, and NADC34 strains, and has posed a threat to the swine industry for over 20 years. To monitor genetic variation in PRRSV-2 GP3 strains in China, we analyzed 618 strains isolated between 1996 to 2023 and constructed phylogenetic trees. Additionally, 60 selected strains were used to analyze nucleotide and amino acid homology. PRRSV GP3 gene exhibited nucleotide identity ranging from 78.2% to 100.0% and amino acid similarity ranging from 74.9% to 99.6%. The GP3 gene in the 60 selected strains consisted of 254 amino acids, and amino acid mutations in the strains primarily occurred in B-cell epitopes, T-cell epitopes, and highly variable regions. The glycosylation sites of the strains used for amino acid sequence comparisons remained unaltered, except for the N29 site in the GD20220303-2022 strain. PRRSV-2 strains in China belong to lineages 1, 3, 5, and 8. Recombination analysis detected two recombination events, involving lineages 1 and 8. In conclusion, this study investigated multiple strains of the PRRSV-2 GP3 gene to explore the prevalence and genetic diversity of the GP3 gene in China from a gene family perspective. The results of the analyses provide a basis for clinical prevention strategies and vaccine development.

Rapamycin's lifespan effect is modulated by mito-nuclear epistasis in Drosophila.

The macrolide drug rapamycin is a benchmark anti-ageing drug, which robustly extends lifespan of diverse organisms. For any health intervention, it is paramount to establish whether benefits are distributed equitably among individuals and populations, and ideally to match intervention to recipients' needs. However, how responses to rapamycin vary is surprisingly understudied. Here we investigate how among-population variation in both mitochondrial and nuclear genetics shapes rapamycin's effects on lifespan. We show that epistatic "mito-nuclear" interactions, between mitochondria and nuclei, modulate the response to rapamycin treatment. Differences manifest as differential demographic effects of rapamycin, with altered age-specific mortality rate. However, a fitness cost of rapamycin early in life does not show a correlated response, suggesting that mito-nuclear epistasis can decouple costs and benefits of treatment. These findings suggest that a deeper understanding of how variation in mitochondrial and nuclear genomes shapes physiology may facilitate tailoring of anti-ageing therapy to individual need.

Genetic diversity, variation and recombination among the human papillomaviruses (HPVs) genomes isolated in China: a comparative genomic and phylogenetic analysis.

Human papillomaviruses (HPVs) are widespread, sexually transmitted group of viruses that infect most individuals at some stage, causing genital warts and cancers. They are members of the Papillomaviridae family, which contains about 400 HPV types. China is among the high HPV burden countries with reported infections of multiple HPV types, accounting for 17.3% of global deaths and 18.2% of global new cases. Thus, understanding the genetic variation and geographic diversity characteristics of HPVs isolated in China is critical for global HPV prevention strategies. Thus, we analyzed the available HPV genome sequences isolated in China that grouped into two categories (alpha- and gamma-papillomaviruses) based on full-length genomes. The most common were HPV-16, -6, -58, and -52 respectively. In addition, four of the novel strains isolated in China, e.g. TG550, JDFY01, CH2, and L55 clustered with the HPV-mSK 159, 244, 201, and 200 respectively. Our phylogeographic network analysis indicated that the L55, TG550, and CH2 are genetically identical to the mSK 200, 046, and 201 respectively, while JDFY01 appeared separately, connected to the mSK-040 following five mutational steps. Also, we found ten recombination events among HPV-6/11 types within their E1, E2, E7, L1/L2 proteins, and Long Control Region ORFs. We achieved the consensus amino acid sequences of HPV proteins and found a conserved stretch of amino acids within E5A of all HPVs circulating in China. These findings offer valued insights into the genetic relationships, distribution, and evolution of the HPVs in China that may assist in adapting effective HPV preventive measures.

Genetic Evaluation of Water Use Efficiency and Nutrient Use Efficiency in Populus deltoides Bartr. ex Marsh. Seedlings in China.

Populus deltoides Bartr. ex Marsh. represents a valuable genetic resource for fast-growing plantations in temperate regions. It holds significant cultivation and breeding potential in northern China. To establish an efficient breeding population of poplar, we studied the genetic variation of P. deltoides from different provenances. Our focus was on genotypes exhibiting high growth rates and efficient water and nutrient use efficiency (WUE and NUE). We evaluated 256 one-year-old seedlings from six provenances, measuring height, ground diameter, total biomass, and leaf carbon and nitrogen isotope abundance (δ13C and δ15N). Our analytical methods included variance analysis, multiple comparisons, mixed linear models, correlation analysis, and principal component analysis. The results showed that the coefficient of variation was highest for δ15N and lowest for δ13C among all traits. Except for δ15N, the effects of intra- and inter-provenance were highly significant (p < 0.01). The rates of variation for all traits ranged from 78.36% to 99.49% for intra-provenance and from 0.51% to 21.64% for inter-provenance. The heritability of all traits in AQ provenance was over 0.65, and all exhibited the highest level except for seedling height. All traits were significantly positively correlated with each other (p < 0.05), while ground diameter, total biomass, and WUE were highly significantly negatively correlated with latitude (p < 0.01). After a comprehensive evaluation, two provenances and eight genotypes were selected. The genetic gains for seedling height, ground diameter, total biomass, WUE, and NUE were 27.46 cm (178-2-106), 3.85 mm (178-2-141), 16.40 g (178-2-141), 0.852‱ (LA05-N15), and 3.145‱ (174-1-2), respectively. Overall, we revealed that the abundant genetic variation in P. deltoides populations mainly comes from intra-provenance differences and evaluated provenances and genotypes. The results of this study will contribute to optimizing and enhancing the breeding process of Chinese poplar and improving the productivity of fast-growing plantations.

Distinct patterns of genetic variation at low-recombining genomic regions represent haplotype structure.

Genomic regions sometimes show patterns of genetic variation distinct from the genome-wide population structure. Such deviations have often been interpreted to represent effects of selection. However, systematic investigation of whether and how non-selective factors, such as recombination rates, can affect distinct patterns has been limited. Here, we associate distinct patterns of genetic variation with reduced recombination rates in a songbird, the Eurasian blackcap (Sylvia atricapilla), using a new reference genome assembly, whole-genome resequenc- ing data and recombination maps. We find that distinct patterns of genetic variation reflect haplotype structure at genomic regions with different prevalence of reduced recombination rate across populations. At low-recombining regions shared in most populations, distinct patterns reflect conspicuous haplotypes segregating in multiple populations. At low-recombining regions found only in a few populations, distinct patterns represent variance among cryptic haplotypes within the low-recombining populations. With simulations, we confirm that these distinct patterns evolve neutrally by reduced recombination rate, on which the effects of selection can be overlaid. Our results highlight that distinct patterns of genetic variation can emerge through evolutionary reduction of local recombination rate. The recombination landscape as an evolvable trait therefore plays an important role determining the heterogeneous distribution of genetic variation along the genome.

Biallelic variants in α-tubulin isotypes cause female infertility characterised as recurrent preimplantation embryo arrest.

BACKGROUND: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the ß-tubulin subunit gene, TUBB8, cause oocyte meiotic arrest and RPEA through a broad spectrum of spindle defects. In contrast, α-tubulin subunit genes are poorly studied in the context of preimplantation embryonic development. METHODS: Whole exome sequencing was performed on the PREA cohort. Functional characterisations of the identified candidate disease-causing variants were validated using Sanger sequencing, bioinformatics, in vitro functional analyses and single-cell RNA-sequencing of arrested embryos. RESULTS: Four homozygous variants were identified in the PREA cohort: two of TUBA1C (p.Gln358Ter and p.Asp444Metfs*42) and two of TUBA4A (p.Arg339Cys and p.Tyr440Ter). These variants cause varying degrees of spindle assembly defects. Additionally, we characterised changes in the human arrested embryo transcriptome carrying TUBA4A variants, with a particular focus on spindle organisation, chromosome segregation and mRNA decay. CONCLUSION: Our findings identified TUBA1C as a novel genetic marker and expanded the genetic and phenotypic spectrum of TUBA4A in female infertility and RPEA, which altogether highlighted the importance of α-tubulin isotypes in preimplantation embryonic development.