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1.
BMC Genomics ; 22(1): 512, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233617

RESUMO

BACKGROUND: Genomic prediction is now an essential technology for genetic improvement in animal and plant breeding. Whereas emphasis has been placed on predicting the breeding values, the prediction of non-additive genetic effects has also been of interest. In this study, we assessed the potential of genomic prediction using non-additive effects for phenotypic prediction in Japanese Black, a beef cattle breed. In addition, we examined the stability of variance component and genetic effect estimates against population size by subsampling with different sample sizes. RESULTS: Records of six carcass traits, namely, carcass weight, rib eye area, rib thickness, subcutaneous fat thickness, yield rate and beef marbling score, for 9850 animals were used for analyses. As the non-additive genetic effects, dominance, additive-by-additive, additive-by-dominance and dominance-by-dominance effects were considered. The covariance structures of these genetic effects were defined using genome-wide SNPs. Using single-trait animal models with different combinations of genetic effects, it was found that 12.6-19.5 % of phenotypic variance were occupied by the additive-by-additive variance, whereas little dominance variance was observed. In cross-validation, adding the additive-by-additive effects had little influence on predictive accuracy and bias. Subsampling analyses showed that estimation of the additive-by-additive effects was highly variable when phenotypes were not available. On the other hand, the estimates of the additive-by-additive variance components were less affected by reduction of the population size. CONCLUSIONS: The six carcass traits of Japanese Black cattle showed moderate or relatively high levels of additive-by-additive variance components, although incorporating the additive-by-additive effects did not improve the predictive accuracy. Subsampling analysis suggested that estimation of the additive-by-additive effects was highly reliant on the phenotypic values of the animals to be estimated, as supported by low off-diagonal values of the relationship matrix. On the other hand, estimates of the additive-by-additive variance components were relatively stable against reduction of the population size compared with the estimates of the corresponding genetic effects.


Assuntos
Genoma , Modelos Genéticos , Animais , Bovinos/genética , Genômica , Fenótipo , Polimorfismo de Nucleotídeo Único , Densidade Demográfica
2.
BMC Plant Biol ; 21(1): 307, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193031

RESUMO

BACKGROUND: Maize rough dwarf disease (MRDD), a widespread disease caused by four pathogenic viruses, severely reduces maize yield and grain quality. Resistance against MRDD is a complex trait that controlled by many quantitative trait loci (QTL) and easily influenced by environmental conditions. So far, many studies have reported numbers of resistant QTL, however, only one QTL have been cloned, so it is especially important to map and clone more genes that confer resistance to MRDD. RESULTS: In the study, a major quantitative trait locus (QTL) qMrdd2, which confers resistance to MRDD, was identified and fine mapped. qMrdd2, located on chromosome 2, was consistently identified in a 15-Mb interval between the simple sequence repeat (SSR) markers D184 and D1600 by using a recombinant inbred line (RIL) population derived from a cross between resistant ("80007") and susceptible ("80044") inbred lines. Using a recombinant-derived progeny test strategy, qMrdd2 was delineated to an interval of 577 kb flanked by markers N31 and N42. We further demonstrated that qMrdd2 is an incompletely dominant resistance locus for MRDD that reduced the disease severity index by 20.4%. CONCLUSIONS: A major resistance QTL (qMrdd2) have been identified and successfully refined into 577 kb region. This locus will be valuable for improving maize variety resistance to MRDD via marker-assisted selection (MAS).


Assuntos
Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/virologia , Locos de Características Quantitativas/genética , Zea mays/genética , Zea mays/virologia , Análise de Variância , Ligação Genética , Endogamia , Modelos Genéticos , Fenótipo , Mapeamento Físico do Cromossomo
3.
FASEB J ; 35(8): e21753, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34233068

RESUMO

Ovarian infertility and subfertility presenting with premature ovarian insufficiency (POI) and diminished ovarian reserve are major issues facing the developed world due to the trend of delaying childbirth. Ovarian senescence and POI represent a continuum of physiological/pathophysiological changes in ovarian follicle functions. Based on advances in whole exome sequencing, evaluation of gene copy variants, together with family-based and genome-wide association studies, we discussed genes responsible for POI and ovarian senescence. We used a gene-centric approach to sort out literature deposited in the Ovarian Kaleidoscope database (http://okdb.appliedbioinfo.net) by sub-categorizing candidate genes as ligand-receptor signaling, meiosis and DNA repair, transcriptional factors, RNA metabolism, enzymes, and others. We discussed individual gene mutations found in POI patients and verification of gene functions in gene-deleted model organisms. Decreased expression of some of the POI genes could be responsible for ovarian senescence, especially those essential for DNA repair, meiosis and mitochondrial functions. We propose to set up a candidate gene panel for targeted sequencing in POI patients together with studies on mitochondria-associated genes in middle-aged subfertile patients.


Assuntos
Ovário/metabolismo , Insuficiência Ovariana Primária/genética , Animais , Reparo do DNA/genética , Bases de Dados Genéticas , Feminino , Estudo de Associação Genômica Ampla , Humanos , Meiose/genética , Menopausa Precoce/genética , Menopausa Precoce/metabolismo , Modelos Genéticos , Reserva Ovariana/genética , Insuficiência Ovariana Primária/metabolismo , Fatores de Transcrição/genética , Sequenciamento Completo do Exoma
4.
Nat Commun ; 12(1): 4237, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244483

RESUMO

Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted magnetic resonance imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.


Assuntos
Encéfalo/fisiologia , Conectoma , Redes Reguladoras de Genes , Rede Nervosa/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Conjuntos de Dados como Assunto , Imagem de Difusão por Ressonância Magnética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Modelos Genéticos , Gêmeos
5.
Nat Commun ; 12(1): 4202, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244507

RESUMO

Biochemical reactions typically depend on the concentrations of the molecules involved, and cell survival therefore critically depends on the concentration of proteins. To maintain constant protein concentrations during cell growth, global mRNA and protein synthesis rates are tightly linked to cell volume. While such regulation is appropriate for most proteins, certain cellular structures do not scale with cell volume. The most striking example of this is the genomic DNA, which doubles during the cell cycle and increases with ploidy, but is independent of cell volume. Here, we show that the amount of histone proteins is coupled to the DNA content, even though mRNA and protein synthesis globally increase with cell volume. As a consequence, and in contrast to the global trend, histone concentrations decrease with cell volume but increase with ploidy. We find that this distinct coordination of histone homeostasis and genome content is already achieved at the transcript level, and is an intrinsic property of histone promoters that does not require direct feedback mechanisms. Mathematical modeling and histone promoter truncations reveal a simple and generalizable mechanism to control the cell volume- and ploidy-dependence of a given gene through the balance of the initiation and elongation rates.


Assuntos
Histonas/biossíntese , Modelos Genéticos , Biossíntese de Proteínas/genética , RNA Mensageiro/biossíntese , Transcrição Genética , DNA Fúngico/genética , Genoma Fúngico , Histonas/genética , Ploidias , Regiões Promotoras Genéticas/genética , RNA Fúngico/biossíntese , RNA Fúngico/genética , RNA Mensageiro/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/biossíntese , Proteínas de Saccharomyces cerevisiae/genética
6.
Nat Genet ; 53(6): 861-868, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34083789

RESUMO

Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.


Assuntos
Regulação da Expressão Gênica , Microglia/metabolismo , Transcrição Genética , Doença de Alzheimer/genética , Humanos , Modelos Genéticos , Locos de Características Quantitativas/genética , Análise de Sequência de RNA , Análise de Célula Única
7.
Nat Commun ; 12(1): 3258, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059679

RESUMO

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.


Assuntos
Carcinogênese/genética , Macroautofagia/genética , Proteínas de Membrana/genética , Modelos Genéticos , Proteínas Musculares/genética , Neoplasias/genética , Algoritmos , Animais , Carcinogênese/patologia , Linhagem Celular Tumoral , Simulação por Computador , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Técnicas de Silenciamento de Genes , Glicogênio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Proteínas de Membrana/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Musculares/metabolismo , Mutação , Neoplasias/mortalidade , Neoplasias/patologia , Via de Pentose Fosfato/genética , Domínios e Motivos de Interação entre Proteínas/genética , Proteoma/genética , RNA-Seq , Análise Serial de Tecidos , Efeito Warburg em Oncologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Nat Commun ; 12(1): 3370, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099647

RESUMO

A sensitive approach to quantitative analysis of transcriptional regulation in diploid organisms is analysis of allelic imbalance (AI) in RNA sequencing (RNA-seq) data. A near-universal practice in such studies is to prepare and sequence only one library per RNA sample. We present theoretical and experimental evidence that data from a single RNA-seq library is insufficient for reliable quantification of the contribution of technical noise to the observed AI signal; consequently, reliance on one-replicate experimental design can lead to unaccounted-for variation in error rates in allele-specific analysis. We develop a computational approach, Qllelic, that accurately accounts for technical noise by making use of replicate RNA-seq libraries. Testing on new and existing datasets shows that application of Qllelic greatly decreases false positive rate in allele-specific analysis while conserving appropriate signal, and thus greatly improves reproducibility of AI estimates. We explore sources of technical overdispersion in observed AI signal and conclude by discussing design of RNA-seq studies addressing two biologically important questions: quantification of transcriptome-wide AI in one sample, and differential analysis of allele-specific expression between samples.


Assuntos
Desequilíbrio Alélico , Biblioteca Gênica , Polimorfismo de Nucleotídeo Único , RNA/genética , Análise de Sequência de RNA/métodos , Transcriptoma/genética , Algoritmos , Alelos , Animais , Feminino , Camundongos da Linhagem 129 , Modelos Genéticos , RNA/metabolismo
9.
Nat Commun ; 12(1): 3628, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131135

RESUMO

We present TensorSignatures, an algorithm to learn mutational signatures jointly across different variant categories and their genomic localisation and properties. The analysis of 2778 primary and 3824 metastatic cancer genomes of the PCAWG consortium and the HMF cohort shows that all signatures operate dynamically in response to genomic states. The analysis pins differential spectra of UV mutagenesis found in active and inactive chromatin to global genome nucleotide excision repair. TensorSignatures accurately characterises transcription-associated mutagenesis in 7 different cancer types. The algorithm also extracts distinct signatures of replication- and double strand break repair-driven mutagenesis by APOBEC3A and 3B with differential numbers and length of mutation clusters. Finally, TensorSignatures reproduces a signature of somatic hypermutation generating highly clustered variants at transcription start sites of active genes in lymphoid leukaemia, distinct from a general and less clustered signature of Polη-driven translesion synthesis found in a broad range of cancer types. In summary, TensorSignatures elucidates complex mutational footprints by characterising their underlying processes with respect to a multitude of genomic variables.


Assuntos
Genômica , Mutação , Neoplasias/genética , Algoritmos , Sequência de Bases , Citidina Desaminase/genética , DNA/genética , Quebras de DNA de Cadeia Dupla , Análise Mutacional de DNA , Reparo do DNA , Replicação do DNA , DNA Polimerase Dirigida por DNA/genética , Epigenômica , Humanos , Antígenos de Histocompatibilidade Menor/genética , Modelos Genéticos , Mutagênese , Proteínas/genética , Transcrição Genética/genética
10.
BMC Plant Biol ; 21(1): 283, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34157965

RESUMO

BACKGROUND: Sesame is a rare example of non-model and minor crop for which numerous genetic loci and candidate genes underlying features of interest have been disclosed at relatively high resolution. These progresses have been achieved thanks to the applications of the genome-wide association study (GWAS) approach. GWAS has benefited from the availability of high-quality genomes, re-sequencing data from thousands of genotypes, extensive transcriptome sequencing, development of haplotype map and web-based functional databases in sesame. RESULTS: In this paper, we reviewed the GWAS methods, the underlying statistical models and the applications for genetic discovery of important traits in sesame. A novel online database SiGeDiD ( http://sigedid.ucad.sn/ ) has been developed to provide access to all genetic and genomic discoveries through GWAS in sesame. We also tested for the first time, applications of various new GWAS multi-locus models in sesame. CONCLUSIONS: Collectively, this work portrays steps and provides guidelines for efficient GWAS implementation in sesame, a non-model crop.


Assuntos
Produtos Agrícolas/genética , Estudo de Associação Genômica Ampla/métodos , Sesamum/genética , Genes de Plantas/genética , Genoma de Planta/genética , Modelos Genéticos
11.
Animal ; 15(5): 100202, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34091273

RESUMO

Community-based sheep breeding programs (CBBPs) have been adopted strategically to improve Bonga sheep, the most popular sheep breed in Ethiopia. The present study was undertaken to estimate genetic parameters and genetic trends for growth traits and inbreeding levels in each Bonga sheep CBBP. Data pertaining to growth traits, spanning a period of seven years (2012-2017), were collected from 14 Bonga sheep CBBPs. Data were analyzed using the General Linear Model procedure of SAS to study the performance of the breed over the years. The genetic parameters were estimated by univariate and multivariate animal model using restricted maximum likelihood method of WOMBAT software. The genetic trends were estimated by the regression of the average breeding values of the animals on the year of birth. The overall least square means ±â€¯SE of BW (kg) were 3.10 ±â€¯0.010, 16.1 ±â€¯0.07, 24.7 ±â€¯0.20, 30.4 ±â€¯0.40 and 34.0 ±â€¯0.84 for birth weight (BWT), weaning weight (WWT), six-month weight (SMWT), nine-month weight (NMWT) and yearling weight (YWT), respectively. Direct heritability estimates from selected models were 0.56 ±â€¯0.030, 0.36 ±â€¯0.030, 0.22 ±â€¯0.040, 0.17 ±â€¯0.070 and 0.13 ±â€¯0.150 for BWT, WWT, SMWT, NMWT and YWT, respectively. Six-month weight was the selection trait and presented positive trends for 10 CBBPs, and negative trends for four CBBPs. Moderate to high heritability estimates and positive genetic trends indicated scope for further improvement of BW. Additionally, the positive and high correlation between BW traits indicated that selection for just one trait would also improve the other traits through correlated responses.


Assuntos
Modelos Genéticos , Animais , Peso ao Nascer , Peso Corporal/genética , Etiópia , Modelos Lineares , Fenótipo , Ovinos/genética , Desmame
12.
Nat Commun ; 12(1): 3896, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162837

RESUMO

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.


Assuntos
Neoplasias Renais/genética , Rim/metabolismo , RNA Mensageiro/genética , RNA-Seq/métodos , Análise de Célula Única/métodos , Transcriptoma , Adulto , Algoritmos , Criança , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Rim/embriologia , Neoplasias Renais/embriologia , Neoplasias Renais/metabolismo , Modelos Genéticos , Transdução de Sinais/genética
13.
Gene ; 793: 145747, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34077778

RESUMO

BACKGROUND: In addition to being a tumour suppressor, TP53 is a suppressor of inflammation, and dysfunction of this gene has been related to autoimmune diseases. Patients with autoimmunity, such as rheumatoid arthritis (RA) have an increased risk of certain cancers, like lymphomas, indicating that some underlying mechanisms may modulate risk of both cancers and autoimmunity. METHODS: We genotyped 5 common genetic variants in TP53 and its main regulators MDM2 and MDM4 in a sample of 942 RA patients and 3,747 healthy controls, and mined previously published GWAS-data, to assess the potential impact of these variants on risk of RA. RESULTS: For the TP53 Arg72Pro polymorphism (rs1042522), MDM4 SNP34091 (rs4245739) and MDM2 SNP285C (rs117039649), we found no association to risk of RA. For MDM2 SNP309 (rs2279744), the minor G-allele was associated with a reduced risk of RA (OR: 0.87; CI: 0.79-0.97). This association was also seen in genotype models (OR: 0.86; CI: 0.74-0.99 and OR: 0.79; CI 0.63-0.99; dominant and recessive model, respectively), but was not validated in a large GWAS data set. For MDM2 del1518 (rs3730485), the minor del-allele was associated with an increased risk of RA in the dominant model (OR: 1.18; CI: 1.02-1.38). Stratifying RA cases and controls into phylogenetic subgroups according to the combined genotypes of all three MDM2 polymorphism, we found individuals with the del158-285-309 genotype del/ins-G/G-T/T to have an increased risk of RA as compared to those with the ins/ins-G/G-G/G genotype (OR: 1.56; CI: 1.18-2.06) indicating opposite effects of the del1518 del-allele and the SNP309 G-allele. CONCLUSION: We find a potential association between the MDM2 del1518 variant and RA, and indications that combinatorial genotypes and haplotypes in the MDM2 locus may be related to RA.


Assuntos
Artrite Reumatoide/genética , Proteínas de Ciclo Celular/genética , Predisposição Genética para Doença , Polimorfismo Genético , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/metabolismo , Mineração de Dados , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Risco , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo
14.
Nat Commun ; 12(1): 3324, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083540

RESUMO

Elucidating the timescale of the evolution of Alphaproteobacteria, one of the most prevalent microbial lineages in marine and terrestrial ecosystems, is key to testing hypotheses on their co-evolution with eukaryotic hosts and Earth's systems, which, however, is largely limited by the scarcity of bacterial fossils. Here, we incorporate eukaryotic fossils to date the divergence times of Alphaproteobacteria, based on the mitochondrial endosymbiosis that mitochondria evolved from an alphaproteobacterial lineage. We estimate that Alphaproteobacteria arose ~1900 million years (Ma) ago, followed by rapid divergence of their major clades. We show that the origin of Rickettsiales, an order of obligate intracellular bacteria whose hosts are mostly animals, predates the emergence of animals for ~700 Ma but coincides with that of eukaryotes. This, together with reconstruction of ancestral hosts, strongly suggests that early Rickettsiales lineages had established previously underappreciated interactions with unicellular eukaryotes. Moreover, the mitochondria-based approach displays higher robustness to uncertainties in calibrations compared with the traditional strategy using cyanobacterial fossils. Further, our analyses imply the potential of dating the (bacterial) tree of life based on endosymbiosis events, and suggest that previous applications using divergence times of the modern hosts of symbiotic bacteria to date bacterial evolution might need to be revisited.


Assuntos
Alphaproteobacteria/classificação , Alphaproteobacteria/genética , Eucariotos/classificação , Eucariotos/genética , Evolução Molecular , Fósseis , Animais , Cianobactérias/classificação , Cianobactérias/genética , Fósseis/história , Fósseis/microbiologia , Genoma Bacteriano , Genoma Mitocondrial , História Antiga , Mitocôndrias/genética , Mitocôndrias/microbiologia , Modelos Biológicos , Modelos Genéticos , Filogenia , Rickettsiales/classificação , Rickettsiales/genética , Simbiose/genética , Fatores de Tempo
15.
Nat Commun ; 12(1): 3498, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108452

RESUMO

Plant genomes vary greatly in size, organization, and architecture. Such structural differences may be highly relevant for inference of genome evolution dynamics and phylogeny. Indeed, microsynteny-the conservation of local gene content and order-is recognized as a valuable source of phylogenetic information, but its use for the inference of large phylogenies has been limited. Here, by combining synteny network analysis, matrix representation, and maximum likelihood phylogenetic inference, we provide a way to reconstruct phylogenies based on microsynteny information. Both simulations and use of empirical data sets show our method to be accurate, consistent, and widely applicable. As an example, we focus on the analysis of a large-scale whole-genome data set for angiosperms, including more than 120 available high-quality genomes, representing more than 50 different plant families and 30 orders. Our 'microsynteny-based' tree is largely congruent with phylogenies proposed based on more traditional sequence alignment-based methods and current phylogenetic classifications but differs for some long-contested and controversial relationships. For instance, our synteny-based tree finds Vitales as early diverging eudicots, Saxifragales within superasterids, and magnoliids as sister to monocots. We discuss how synteny-based phylogenetic inference can complement traditional methods and could provide additional insights into some long-standing controversial phylogenetic relationships.


Assuntos
Genoma de Planta/genética , Magnoliopsida/genética , Filogenia , Sintenia , Evolução Molecular , Genes de Plantas/genética , Magnoliopsida/classificação , Modelos Genéticos , Família Multigênica/genética
16.
Trop Anim Health Prod ; 53(3): 349, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34101031

RESUMO

The objective of this study was to evaluate the accuracy of genomic predictions of growth traits in Nellore cattle. Data from 5064 animals belonging to farms that participate in the Conexão DeltaGen and PAINT breeding programs were used. Genotyping was performed with the Illumina BovineHD BeadChip (777,962 SNPs). After quality control of the genomic data, 412,993 SNPs were used. Deregressed EBVs (DEBVs) were calculated using the estimated breeding values (EBVs) and accuracies of birth weight (BW), weight gain from birth to weaning (GBW), postweaning weight gain (PWG), yearling height (YH), and cow weight (CW) provided by GenSys. Three models were used to estimate marker effects: genomic best linear unbiased prediction (GBLUP), BayesCπ, and improved Bayesian least absolute shrinkage and selection operator (IBLASSO). The prediction ability of genomic estimated breeding value (GEBVs) was estimated by the average Pearson correlation between DEBVs and GEBVs, predicted with the different methodologies in the validation populations. The regression coefficients of DEBVs on GEBVs in the validation population were calculated and used as indicators of prediction bias of GEBV. In general, the Bayesian methods provided slightly more accurate predictions of genomic breeding values than GBLUP. The BayesCπ and IBLASSO were similar for all traits (BW, GBW, PWG, and YH), except for CW. Thus, there does not seem to be a more suitable method for the estimation of SNP effects and genomic breeding values. Bayesian regression models are of interest for future applications of genomic selection in this population, but further improvements are needed to reduce deflation of their predictions.


Assuntos
Genoma , Genômica , Animais , Teorema de Bayes , Bovinos/genética , Feminino , Genótipo , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único
17.
Nat Commun ; 12(1): 3551, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112792

RESUMO

Species harbor extensive structural variation underpinning recent adaptive evolution. However, the causality between genomic features and the induction of new rearrangements is poorly established. Here, we analyze a global set of telomere-to-telomere genome assemblies of a fungal pathogen of wheat to establish a nucleotide-level map of structural variation. We show that the recent emergence of pesticide resistance has been disproportionally driven by rearrangements. We use machine learning to train a model on structural variation events based on 30 chromosomal sequence features. We show that base composition and gene density are the major determinants of structural variation. Retrotransposons explain most inversion, indel and duplication events. We apply our model to Arabidopsis thaliana and show that our approach extends to more complex genomes. Finally, we analyze complete genomes of haploid offspring in a four-generation pedigree. Meiotic crossover locations are enriched for new rearrangements consistent with crossovers being mutational hotspots. The model trained on species-wide structural variation accurately predicts the position of >74% of newly generated variants along the pedigree. The predictive power highlights causality between specific sequence features and the induction of chromosomal rearrangements. Our work demonstrates that training sequence-derived models can accurately identify regions of intrinsic DNA instability in eukaryotic genomes.


Assuntos
Ascomicetos/genética , Ascomicetos/patogenicidade , Cromossomos/genética , Variação Genética , Genoma , Genômica/métodos , Aprendizado de Máquina , Meiose/genética , Arabidopsis/genética , Cromossomos/metabolismo , Simulação por Computador , Troca Genética , Eucariotos/genética , Evolução Molecular , Genes Duplicados , Estudo de Associação Genômica Ampla , Mutação INDEL , Modelos Genéticos , Linhagem , Filogenia , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Retroelementos/genética , Inversão de Sequência
18.
Phys Rev Lett ; 126(21): 218102, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34114848

RESUMO

We introduce a statistical and linear response theory of selective conduction in biological ion channels with multiple binding sites and possible point mutation. We derive an effective grand-canonical ensemble and generalized Einstein relations for the selectivity filter, assuming strongly coordinated ionic motion, and allowing for ionic Coulomb blockade. The theory agrees well with data from the KcsA K^{+} channel and a mutant. We show that the Eisenman relations for thermodynamic selectivity follow from the condition for fast conduction and find that maximum conduction requires the binding sites to be nearly identical.


Assuntos
Canais Iônicos/química , Canais Iônicos/genética , Modelos Biológicos , Modelos Químicos , Mutação Puntual , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Fenômenos Biofísicos , Canais Iônicos/metabolismo , Modelos Genéticos , Modelos Moleculares , Canais de Potássio/química , Canais de Potássio/genética , Canais de Potássio/metabolismo , Termodinâmica
19.
BMC Ecol Evol ; 21(1): 110, 2021 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-34092214

RESUMO

BACKGROUND: Mendelian inheritance is a fundamental law of genetics. When we consider two genomes in a diploid cell, a heterozygote's phenotype is dominated by a particular homozygote according to the law of dominance. Classical Mendelian dominance is concerned with which proteins are dominant, and is usually based on simple genotype-phenotype relationship in which one gene regulates one phenotype. However, in reality, some interactions between genes can exist, resulting in deviations from Mendelian dominance. Whether and how Mendelian dominance is generalized to the phenotypes of gene expression determined by gene regulatory networks (GRNs) remains elusive. RESULTS: Here, by using the numerical evolution of diploid GRNs, we discuss whether the dominance of phenotype evolves beyond the classical Mendelian case of one-to-one genotype-phenotype relationship. We examine whether complex genotype-phenotype relationship can achieve Mendelian dominance at the expression level by a pair of haplotypes through the evolution of the GRN with interacting genes. This dominance is defined via a pair of haplotypes that differ from each other but have a common phenotype given by the expression of target genes. We numerically evolve the GRN model for a diploid case, in which two GRN matrices are added to give gene expression dynamics and simulate evolution with meiosis and recombination. Our results reveal that group Mendelian dominance evolves even under complex genotype-phenotype relationship. Calculating the degree of dominance shows that it increases through the evolution, correlating closely with the decrease in phenotypic fluctuations and the increase in robustness to initial noise. We also demonstrate that the dominance of gene expression patterns evolves concurrently. This evolution of group Mendelian dominance and pattern dominance is associated with phenotypic robustness against meiosis-induced genome mixing, whereas sexual recombination arising from the mixing of genomes from the parents further enhances dominance and robustness. Due to this dominance, the robustness to genetic differences increases, while optimal fitness is sustained to a significant difference between the two genomes. CONCLUSION: Group Mendelian dominance and gene-expression pattern dominance are achieved associated with the increase in phenotypic robustness to noise.


Assuntos
Modelos Genéticos , Expressão Gênica , Genótipo , Mutação , Fenótipo
20.
Mol Ecol ; 30(12): 2710-2723, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955064

RESUMO

A key step in understanding the genetic basis of different evolutionary outcomes (e.g., adaptation) is to determine the roles played by different mutation types (e.g., SNPs, translocations and inversions). To do this we must simultaneously consider different mutation types in an evolutionary framework. Here, we propose a research framework that directly utilizes the most important characteristics of mutations, their population genetic effects, to determine their relative evolutionary significance in a given scenario. We review known population genetic effects of different mutation types and show how these may be connected to different evolutionary outcomes. We provide examples of how to implement this framework and pinpoint areas where more data, theory and synthesis are needed. Linking experimental and theoretical approaches to examine different mutation types simultaneously is a critical step towards understanding their evolutionary significance.


Assuntos
Evolução Biológica , Genética Populacional , Modelos Genéticos , Adaptação Fisiológica , Inversão Cromossômica , Mutação , Taxa de Mutação , Densidade Demográfica , Seleção Genética
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