RESUMO
The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcaseCYP2D6, a gene that metabolizes approximately 25% of all prescribed drugs. We also show how the historical underrepresentation of females in clinical trials has led to significantly more adverse drug reactions in females than in males.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sexismo , Masculino , Humanos , Feminino , FarmacogenéticaRESUMO
Understanding the quantitative genetics of crops has been and will continue to be central to maintaining and improving global food security. We outline four stages that plant breeding either has already achieved or will probably soon achieve. Top-of-the-line breeding programs are currently in Breeding 3.0, where inexpensive, genome-wide data coupled with powerful algorithms allow us to start breeding on predicted instead of measured phenotypes. We focus on three major questions that must be answered to move from current Breeding 3.0 practices to Breeding 4.0: ( a) How do we adapt crops to better fit agricultural environments? ( b) What is the nature of the diversity upon which breeding can act? ( c) How do we deal with deleterious variants? Answering these questions and then translating them to actual gains for farmers will be a significant part of achieving global food security in the twenty-first century.
Assuntos
Produtos Agrícolas/genética , Genoma de Planta/genética , Melhoramento Vegetal , Locos de Características Quantitativas/genética , Genômica , HumanosRESUMO
Kinesin-5 motor proteins play essential roles during mitosis in most organisms. Their tetrameric structure and plus-end-directed motility allow them to bind to and move along antiparallel microtubules, thereby pushing spindle poles apart to assemble a bipolar spindle. Recent work has shown that the C-terminal tail is particularly important to kinesin-5 function: The tail affects motor domain structure, ATP hydrolysis, motility, clustering, and sliding force measured for purified motors, as well as motility, clustering, and spindle assembly in cells. Because previous work has focused on presence or absence of the entire tail, the functionally important regions of the tail remain to be identified. We have therefore characterized a series of kinesin-5/Cut7 tail truncation alleles in fission yeast. Partial truncation causes mitotic defects and temperature-sensitive growth, while further truncation that removes the conserved BimC motif is lethal. We compared the sliding force generated by cut7 mutants using a kinesin-14 mutant background in which some microtubules detach from the spindle poles and are pushed into the nuclear envelope. These Cut7-driven protrusions decreased as more of the tail was truncated, and the most severe truncations produced no observable protrusions. Our observations suggest that the C-terminal tail of Cut7p contributes to both sliding force and midzone localization. In the context of sequential tail truncation, the BimC motif and adjacent C-terminal amino acids are particularly important for sliding force. In addition, moderate tail truncation increases midzone localization, but further truncation of residues N-terminal to the BimC motif decreases midzone localization.
Assuntos
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Cinesinas/genética , Fuso Acromático/genética , Microtúbulos , Alelos , Ciclo Celular , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genéticaRESUMO
Arthropod silk is vital to the evolutionary success of hundreds of thousands of species. The primary proteins in silks are often encoded by long, repetitive gene sequences. Until recently, sequencing and assembling these complex gene sequences has proven intractable given their repetitive structure. Here, using high-quality long-read sequencing, we show that there is extensive variation-both in terms of length and repeat motif order-between alleles of silk genes within individual arthropods. Further, this variation exists across two deep, independent origins of silk which diverged more than 500 Mya: the insect clade containing caddisflies and butterflies and spiders. This remarkable convergence in previously overlooked patterns of allelic variation across multiple origins of silk suggests common mechanisms for the generation and maintenance of structural protein-coding genes. Future genomic efforts to connect genotypes to phenotypes should account for such allelic variation.
Assuntos
Borboletas , Fibroínas , Aranhas , Animais , Seda/química , Sequência de Aminoácidos , Fibroínas/química , Alelos , Insetos/genética , Borboletas/genética , Variação Genética , Aranhas/genética , Proteínas de Insetos/genética , FilogeniaRESUMO
This review explores the integration of wild grass-derived alleles into modern bread wheat breeding to tackle the challenges of climate change and increasing food demand. With a focus on synthetic hexaploid wheat, this review highlights the potential of genetic variability in wheat wild relatives, particularly Aegilops tauschii, for improving resilience to multifactorial stresses like drought, heat, and salinity. The evolutionary journey of wheat (Triticum spp.) from diploid to hexaploid species is examined, revealing significant genetic contributions from wild grasses. We also emphasize the importance of understanding incomplete lineage sorting in the genomic evolution of wheat. Grasping this information is crucial as it can guide breeders in selecting the appropriate alleles from the gene pool of wild relatives to incorporate into modern wheat varieties. This approach improves the precision of phylogenetic relationships and increases the overall effectiveness of breeding strategies. This review also addresses the challenges in utilizing the wheat wild genetic resources, such as the linkage drag and cross-compatibility issues. Finally, we culminate the review with future perspectives, advocating for a combined approach of high-throughput phenotyping tools and advanced genomic techniques to comprehensively understand the genetic and regulatory architectures of wheat under stress conditions, paving the way for more precise and efficient breeding strategies.
Assuntos
Alelos , Melhoramento Vegetal , Estresse Fisiológico , Triticum , Triticum/genética , Triticum/fisiologia , Melhoramento Vegetal/métodos , Estresse Fisiológico/genética , Genoma de Planta/genética , Poaceae/genética , Poaceae/fisiologia , Aegilops/genética , Variação Genética , Poliploidia , FilogeniaRESUMO
Adaptive evolution to cellular stress is a process implicated in a wide range of biological and clinical phenomena. Two major routes of adaptation have been identified: non-genetic changes, which allow expression of different phenotypes in novel environments, and genetic variation achieved by selection of fitter phenotypes. While these processes are broadly accepted, their temporal and epistatic features in the context of cellular evolution and emerging drug resistance are contentious. In this manuscript, we generated hypomorphic alleles of the essential nuclear pore complex (NPC) gene NUP58. By dissecting early and long-term mechanisms of adaptation in independent clones, we observed that early physiological adaptation correlated with transcriptome rewiring and upregulation of genes known to interact with the NPC; long-term adaptation and fitness recovery instead occurred via focal amplification of NUP58 and restoration of mutant protein expression. These data support the concept that early phenotypic plasticity allows later acquisition of genetic adaptations to a specific impairment. We propose this approach as a genetic model to mimic targeted drug therapy in human cells and to dissect mechanisms of adaptation.
Assuntos
Adaptação Fisiológica/genética , Alelos , Receptor Quinase 1 Acoplada a Proteína G/genética , Aptidão Genética , N-Glicosil Hidrolases/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Receptor Quinase 1 Acoplada a Proteína G/metabolismo , Edição de Genes , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HCT116 , Células HEK293 , Haploidia , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mutação , Células Mieloides/metabolismo , Células Mieloides/patologia , N-Glicosil Hidrolases/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Transdução de Sinais , Transcriptoma , Proteína Vermelha FluorescenteRESUMO
SignificanceProteins are the machinery which execute essential cellular functions. However, measuring their abundance within an organism can be difficult and resource-intensive. Cells use a variety of mechanisms to control protein synthesis from mRNA, including short open reading frames (uORFs) that lie upstream of the main coding sequence. Ribosomes can preferentially translate uORFs instead of the main coding sequence, leading to reduced translation of the main protein. In this study, we show that uORF sequence variation between individuals can lead to different rates of protein translation and thus variable protein abundances. We also demonstrate that natural variation in uORFs occurs frequently and can be linked to whole-plant phenotypes, indicating that uORF sequence variation likely contributes to plant adaptation.
Assuntos
Biossíntese de Proteínas , Zea mays , Regiões 5' não Traduzidas , Fases de Leitura Aberta/genética , Biossíntese de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Zea mays/genética , Zea mays/metabolismoRESUMO
BACKGROUND: The identification of low-frequency haplotypes, never observed in homozygous state in a population, is considered informative on the presence of potentially harmful alleles (candidate alleles), putatively involved in inbreeding depression. Although identification of candidate alleles is challenging, studies analyzing the dynamics of potentially harmful alleles are lacking. A pedigree of the highly endangered Gochu Asturcelta pig breed, including 471 individuals belonging to 51 different families with at least 5 offspring each, was genotyped using the Axiom PigHDv1 Array (658,692 SNPs). Analyses were carried out on four different cohorts defined according to pedigree depth and at the whole population (WP) level. RESULTS: The 4,470 Linkage Blocks (LB) identified in the Base Population (10 individuals), gathered a total of 16,981 alleles in the WP. Up to 5,466 (32%) haplotypes were statistically considered candidate alleles, 3,995 of them (73%) having one copy only. The number of alleles and candidate alleles varied across cohorts according to sample size. Up to 4,610 of the alleles identified in the WP (27% of the total) were present in one cohort only. Parentage analysis identified a total of 67,742 parent-offspring incompatibilities. The number of mismatches varied according to family size. Parent-offspring inconsistencies were identified in 98.2% of the candidate alleles and 100% of the LB in which they were located. Segregation analyses informed that most potential candidate alleles appeared de novo in the pedigree. Only 17 candidate alleles were identified in the boar, sow, and paternal and maternal grandparents and were considered segregants. CONCLUSIONS: Our results suggest that neither mutation nor recombination are the major forces causing the apparition of candidate alleles. Their occurrence is more likely caused by Allele-Drop-In events due to SNP calling errors. New alleles appear when wrongly called SNPs are used to construct haplotypes. The presence of candidate alleles in either parents or grandparents of the carrier individuals does not ensure that they are true alleles. Minimum Allele Frequency thresholds may remove informative alleles. Only fully segregant candidate alleles should be considered potentially harmful alleles. A set of 16 candidate genes, potentially involved in inbreeding depression, is described.
Assuntos
Alelos , Haplótipos , Linhagem , Polimorfismo de Nucleotídeo Único , Animais , Suínos/genética , Dinâmica Populacional , Feminino , Masculino , Frequência do GeneRESUMO
The oomycete Phytophthora cinnamomi is a devastating plant pathogen with a notably broad host range. It is the causal agent of Phytophthora root rot (PRR), arguably the most economically important yield-limiting disease in Persea americana (avocado). Despite this, our understanding of the mechanisms P. cinnamomi employs to infect and successfully colonize avocado remains limited, particularly regarding the pathogen's ability to maintain its biotrophic and necrotrophic lifestyles during infection. The pathogen utilises a large repertoire of effector proteins which function in facilitating and establishing disease in susceptible host plants. Crinkling and necrosis effectors (CRN/Crinklers) are suspected to manipulate cell death to aid in maintenance of the pathogens biotrophic and necrotrophic lifestyles during different stages of infection. The current study identified 25 P. cinnamomi CRN effectors from the GKB4 genome using an HMM profile and assigned putative function to them as either cell death inducers or suppressors. Function was assigned to 10 PcinCRNs by analysing their RNA-seq expression profiles, relatedness to other functionally characterised Phytophthora CRNs and tertiary protein predictions. The full-length coding sequences for these PcinCRNs were confirmed by Sanger sequencing, six of which were found to have two divergent alleles. The presence of alleles indicates that the proteins encoded may perform contradicting functions in cell death manipulation, or function in different host plant species. Overall, this study provides a foundation for future research on P. cinnamomi infection and cell death manipulation mechanisms.
Assuntos
Morte Celular , Persea , Phytophthora , Doenças das Plantas , Phytophthora/fisiologia , Phytophthora/genética , Phytophthora/patogenicidade , Persea/microbiologia , Persea/genética , Doenças das Plantas/microbiologiaRESUMO
The reduced penetrance of TBP intermediate alleles and the recently proposed possible digenic TBP/STUB1 inheritance raised questions on the possible mechanism involved opening a debate on the existence of SCA48 as a monogenic disorder. We here report clinical and genetic results of two apparently unrelated patients carrying the same STUB1 variant(c.244G > T;p.Asp82Tyr) with normal TBP alleles and a clinical picture fully resembling SCA48, including cerebellar ataxia, dysarthria and mild cognitive impairment. This report provides supportive evidence that this specific ataxia can also occur as a monogenic disease, considering classical TBP allelic ranges.
Assuntos
Linhagem , Ataxias Espinocerebelares , Ubiquitina-Proteína Ligases , Humanos , Ataxias Espinocerebelares/genética , Masculino , Feminino , Ubiquitina-Proteína Ligases/genética , Pessoa de Meia-Idade , Proteína de Ligação a TATA-Box/genética , Adulto , Alelos , Mutação/genéticaRESUMO
Chromosome rearrangements are often implicated with genomic divergence and are proposed to be associated with species evolution. Rearrangements alter the genomic structure and interfere with homologous recombination by isolating a portion of the genome. Integration of multiplatform next-generation DNA sequencing technologies has enabled putative identification of chromosome rearrangements in many taxa; however, integrating these data sets with cytogenetics is still uncommon beyond model genetic organisms. Therefore, to achieve the ultimate goal for the genomic classification of eukaryotic organisms, physical chromosome mapping remains critical. The ridge-tailed goannas (Varanus acanthurus BOULENGER) are a group of dwarf monitor lizards comprised of several species found throughout northern Australia. These lizards exhibit extreme divergence at both the genic and chromosomal levels. The chromosome polymorphisms are widespread extending across much of their distribution, raising the question if these polymorphisms are homologous within the V. acanthurus complex. We used a combined genomic and cytogenetic approach to test for homology across divergent populations with morphologically similar chromosome rearrangements. We showed that more than one chromosome pair was involved with the widespread rearrangements. This finding provides evidence to support de novo chromosome rearrangements have occurred within populations. These chromosome rearrangements are characterized by fixed allele differences originating in the vicinity of the centromeric region. We then compared this region with several other assembled genomes of reptiles, chicken, and the platypus. We demonstrated that the synteny of genes in Reptilia remains conserved despite centromere repositioning across these taxa.
Assuntos
Evolução Molecular , Lagartos , Animais , Alelos , Lagartos/genética , Centrômero/genética , Rearranjo GênicoRESUMO
One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-II risk alleles for developing Hashimoto's thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (thyroid peroxidase, TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective alleles for HT disease. Then, in silico analysis was conducted to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacities to HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles and DRB1*13:01 as a potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002; OR, 3.97) and DRB1*03:01 ~ DQB1*02:01 (Pc = 0.004; OR, 2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles for discrimination of the susceptible from healthy individuals (AUC, 0.70; P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herpes virus and sequence 151-199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individuals carrying HLA risk alleles which can also be related to herpes virus infection.
Assuntos
Alelos , Autoantígenos , Epitopos , Predisposição Genética para Doença , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Doença de Hashimoto , Humanos , Masculino , Feminino , Doença de Hashimoto/genética , Doença de Hashimoto/imunologia , Adulto , Irã (Geográfico) , Cadeias HLA-DRB1/genética , Cadeias beta de HLA-DQ/genética , Autoantígenos/imunologia , Autoantígenos/genética , Epitopos/imunologia , Epitopos/genética , Pessoa de Meia-Idade , Estudos de Casos e Controles , Iodeto Peroxidase/genética , Iodeto Peroxidase/imunologia , Haplótipos , Genótipo , Frequência do GeneRESUMO
HLA alleles are representative of ethnicities and may play important roles in predisposition to hematological disorders. We analyzed DNA samples for HLA-A, -B, -C, -DRB1, and -DQB1 loci, from 1550 patients and 4450 potential related donors by PCR-SSO (Polymerase chain reaction sequence-specific oligonucleotides) and estimated allele frequencies in donors and patients from 1550 families who underwent bone marrow transplantation (BMT) in Egypt. We also studied the association between HLA allele frequencies and incidence of acute myeloid leukemia, acute lymphoblastic leukemia, and severe aplastic anemia. The most frequently observed HLA class I alleles were HLA- A*01:01 (16.9%), A*02:01 (16.1%), B*41:01 (8.7%), B*49:01 (7.3%), C*06:02 (25.1%), and C*07:01 (25.1%), and the most frequently observed class II alleles were HLA-DRB1*11:01 (11.8%), DRB1*03:01 (11.6%), DQB1*03:01 (27.5%), and DQB1*05:01 (18.9%). The most frequently observed haplotypes were A*33:01~B*14:02 ~ DRB1*01:02 (2.35%) and A*01:01~B*52:01~DRB1*15:01 (2.11%). HLA-DRB1*07:01 was associated with higher AML odds (OR, 1.26; 95% CI, 1.02-1.55; p = 0.030). Only HLA-B38 antigen showed a trend towards increased odds of ALL (OR, 1.52; 95% CI, 1.00-2.30; p = 0.049) HLA-A*02:01, -B*14:02, and -DRB1*15:01 were associated with higher odds of SAA (A*02:01: OR, 1.35; 95% CI, 1.07-1.70; p = 0.010; B*14:02: OR, 1.43; 95% CI, 1.06-1.93; p = 0.020; DRB1*15:01: OR, 1.32; 95% CI, 1.07-1.64; p = 0.011). This study provides estimates of HLA allele and haplotype frequencies and their association with hematological disorders in an Egyptian population.
Assuntos
Alelos , Transplante de Medula Óssea , Frequência do Gene , Haplótipos , Doenças Hematológicas , Humanos , Egito , Masculino , Feminino , Adolescente , Adulto , Criança , Doenças Hematológicas/genética , Pré-Escolar , Transplante Homólogo , Leucemia Mieloide Aguda/genética , Adulto Jovem , Antígenos HLA/genética , Pessoa de Meia-Idade , Predisposição Genética para Doença , Lactente , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Anemia Aplástica/genéticaRESUMO
Soybean is a crucial crop for the Brazilian economy, but it faces challenges from the biotrophic fungus Phakopsora pachyrhizi, which causes Asian Soybean Rust (ASR). In this study, we aimed to identify SNPs associated with resistance within the Rpp1 locus, which is effective against Brazilian ASR populations. We employed GWAS and re-sequencing analyzes to pinpoint SNP markers capable of differentiating between soybean accessions harboring the Rpp1, Rpp1-b and other alternative alleles in the Rpp1 locus and from susceptible soybean cultivars. Seven SNP markers were found to be associated with ASR resistance through GWAS, with three of them defining haplotypes that efficiently distinguished the accessions based on their ASR resistance and source of the Rpp gene. These haplotypes were subsequently validated using a bi-parental population and a diverse set of Rpp sources, demonstrating that the GWAS markers co-segregate with ASR resistance. We then examined the presence of these haplotypes in a diverse set of soybean genomes worldwide, finding a few new potential sources of Rpp1/Rpp1-b. Further genomic sequence analysis revealed nucleotide differences within the genes present in the Rpp1 locus, including the ULP1-NBS-LRR genes, which are potential R gene candidates. These results provide valuable insights into ASR resistance in soybean, thus helping the development of resistant soybean varieties through genetic breeding programs.
Assuntos
Alelos , Resistência à Doença , Estudo de Associação Genômica Ampla , Glycine max , Phakopsora pachyrhizi , Doenças das Plantas , Polimorfismo de Nucleotídeo Único , Glycine max/genética , Glycine max/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Resistência à Doença/genética , Phakopsora pachyrhizi/fisiologia , Phakopsora pachyrhizi/genética , Haplótipos , Genes de Plantas , Basidiomycota/fisiologiaRESUMO
BACKGROUND: Semi-dwarfing alleles are used widely in cereals to confer improved lodging resistance and assimilate partitioning. The most widely deployed semi-dwarfing alleles in rice and barley encode the gibberellin (GA)-biosynthetic enzyme GA 20-OXIDASE2 (GA20OX2). The hexaploid wheat genome carries three homoeologous copies of GA20OX2, and because of functional redundancy, loss-of-function alleles of a single homoeologue would not be selected in wheat breeding programmes. Instead, approximately 70% of wheat cultivars carry gain-of-function mutations in REDUCED HEIGHT 1 (RHT1) genes that encode negative growth regulators and are degraded in response to GA. Semi-dwarf Rht-B1b or Rht-D1b alleles encode proteins that are insensitive to GA-mediated degradation. However, because RHT1 is expressed ubiquitously these alleles have pleiotropic effects that confer undesirable traits in some environments. RESULTS: We have applied reverse genetics to combine loss-of-function alleles in all three homoeologues of wheat GA20OX2 and its paralogue GA20OX1 and evaluated their performance in three years of field trials. ga20ox1 mutants exhibited a mild height reduction (approximately 3%) suggesting GA20OX1 plays a minor role in stem elongation in wheat. ga20ox2 mutants have reduced GA1 content and are 12-32% shorter than their wild-type segregants, comparable to the effect of the Rht-D1b 'Green Revolution' allele. The ga20ox2 mutants showed no significant negative effects on yield components in the spring wheat variety 'Cadenza'. CONCLUSIONS: Our study demonstrates that chemical mutagenesis can expand genetic variation in polyploid crops to uncover novel alleles despite the difficulty in identifying appropriate mutations for some target genes and the negative effects of background mutations. Field experiments demonstrate that mutations in GA20OX2 reduce height in wheat, but it will be necessary to evaluate the effect of these alleles in different genetic backgrounds and environments to determine their value in wheat breeding as alternative semi-dwarfing alleles.
Assuntos
Fenótipo , Proteínas de Plantas , Triticum , Triticum/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação , Oryza/genética , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Alelos , Giberelinas/metabolismo , Genes de PlantasRESUMO
BACKGROUND: Rice (Oryza sativa L.) is one of the globally important staple food crops, and yield-related traits are prerequisites for improved breeding efficiency in rice. Here, we used six different genome-wide association study (GWAS) models for 198 accessions, with 553,229 single nucleotide markers (SNPs) to identify the quantitative trait nucleotides (QTNs) and candidate genes (CGs) governing rice yield. RESULTS: Amongst the 73 different QTNs in total, 24 were co-localized with already reported QTLs or loci in previous mapping studies. We obtained fifteen significant QTNs, pathway analysis revealed 10 potential candidates within 100kb of these QTNs that are predicted to govern plant height, days to flowering, and plot yield in rice. Based on their superior allelic information in 20 elite and 6 inferior genotypes, we found a higher percentage of superior alleles in the elite genotypes in comparison to inferior genotypes. Further, we implemented expression analysis and enrichment analysis enabling the identification of 73 candidate genes and 25 homologues of Arabidopsis, 19 of which might regulate rice yield traits. Of these candidate genes, 40 CGs were found to be enriched in 60 GO terms of the studied traits for instance, positive regulator metabolic process (GO:0010929), intracellular part (GO:0031090), and nucleic acid binding (GO:0090079). Haplotype and phenotypic variation analysis confirmed that LOC_OS09G15770, LOC_OS02G36710 and LOC_OS02G17520 are key candidates associated with rice yield. CONCLUSIONS: Overall, we foresee that the QTNs, putative candidates elucidated in the study could summarize the polygenic regulatory networks controlling rice yield and be useful for breeding high-yielding varieties.
Assuntos
Estudo de Associação Genômica Ampla , Oryza , Mapeamento Cromossômico , Oryza/genética , Melhoramento Vegetal , Locos de Características Quantitativas/genéticaRESUMO
Drought stress profoundly hampers both plant growth and crop yield. To combat this, plants have evolved intricate transcriptional regulation mechanisms as a pivotal strategy. Through a genetic screening with rice genome-scale mutagenesis pool under drought stress, we identified an APETALA2/Ethylene Responsive Factor, namely OsERF103, positively responds to drought tolerance in rice. Combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we pinpointed c. 1000 genes directly influenced by OsERF103. Further results revealed that OsERF103 interacts with Stress-responsive NAC1 (SNAC1), a positive regulator of drought tolerance in rice, to synergistically regulate the expression of key drought-related genes, such as OsbZIP23. Moreover, we found that OsERF103 recruits a Su(var)3-9,enhancer of zeste and trithorax-domain group protein 705, which encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase to specifically affect the deposition of H3K4me3 at loci like OsbZIP23 and other genes linked to dehydration responses. Additionally, the natural alleles of OsERF103 are selected during the domestication of both indica and japonica rice varieties and exhibit significant geographic distribution. Collectively, our findings have unfurled a comprehensive mechanistic framework underlying the OsERF103-mediated cascade regulation of drought response. This discovery not only enhances our understanding of drought signaling but also presents a promising avenue for the genetic improvement of drought-tolerant rice cultivars.
Assuntos
Oryza , Oryza/metabolismo , Estresse Fisiológico/genética , Secas , Plantas Geneticamente Modificadas/metabolismo , Sequências Reguladoras de Ácido Nucleico , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Linear barriers pose significant challenges for wildlife gene flow, impacting species persistence, adaptation, and evolution. While numerous studies have examined the effects of linear barriers (e.g., fences and roadways) on partitioning urban and non-urban areas, understanding their influence on gene flow within cities remains limited. Here, we investigated the impact of linear barriers on coyote (Canis latrans) population structure in Seattle, Washington, where major barriers (i.e., interstate highways and bodies of water) divide the city into distinct quadrants. Just under 1000 scats were collected to obtain genetic data between January 2021 and December 2022, allowing us to identify 73 individual coyotes. Notably, private allele analysis underscored limited interbreeding among quadrants. When comparing one quadrant to each other, there were up to 16 private alleles within a single quadrant, representing nearly 22% of the population allelic diversity. Our analysis revealed weak isolation by distance, and despite being a highly mobile species, genetic structuring was apparent between quadrants even with extremely short geographic distance between individual coyotes, implying that Interstate 5 and the Ship Canal act as major barriers. This study uses coyotes as a model species for understanding urban gene flow and its consequences in cities, a crucial component for bolstering conservation of rarer species and developing wildlife friendly cities.
Assuntos
Coiotes , Fluxo Gênico , Genética Populacional , Coiotes/genética , Animais , Washington , Variação Genética , Cidades , Alelos , Repetições de Microssatélites/genéticaRESUMO
In the realm of agricultural sustainability, the utilization of plant genetic resources (PGRs) for enhanced disease resistance is paramount. Preservation efforts in genebanks are justified by their potential contributions to future crop improvement. To capitalize on the potential of PGRs, we focused on a barley core collection from the German ex situ genebank, and contrasted it with a European elite collection. The phenotypic assessment included 812 PGRs and 298 elites with a particular emphasis on four disease traits (Puccinia hordei, Blumeria graminis hordei, Ramularia collo-cygni, and Rhynchosporium commune). An integrated genome-wide association study, employing both Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) and a linear mixed model, was performed to unravel the genetic underpinnings of disease resistance. A total of 932 marker-trait associations were identified and assigned to 49 quantitative trait loci. The accumulation of novel and rare resistance alleles significantly bolstered the overall resistance level in PGRs. Three PGR donors with high counts of novel/rare alleles and exhibited exceptional resistance to leaf rust and powdery mildew were identified, offering promise for targeted pre-breeding goals and enhanced resilience in forthcoming varieties. Our findings underscore the critical contribution of PGRs to strengthening crop resilience and advancing sustainable agricultural practices.
RESUMO
In Athreya et al. (2021), models from population genetics were used to define stochastic dynamics in the space of graphons arising as continuum limits of dense graphs. In the present paper we exhibit an example of a simple neutral population genetics model for which this dynamics is a Markovian diffusion that can be characterized as the solution of a martingale problem. In particular, we consider a Markov chain in the space of finite graphs that resembles a Moran model with resampling and mutation. We encode the finite graphs as graphemes, which can be represented as a triple consisting of a vertex set (or more generally, a topological space), an adjacency matrix, and a sampling (Borel) measure. We equip the space of graphons with convergence of sample subgraph densities and show that the grapheme-valued Markov chain converges to a grapheme-valued diffusion as the number of vertices goes to infinity. We show that the grapheme-valued diffusion has a stationary distribution that is linked to the Griffiths-Engen-McCloskey (GEM) distribution. In a companion paper (Greven et al. 2023), we build up a general theory for obtaining grapheme-valued diffusions via genealogies of models in population genetics.