Sexual reproduction contributes to the evolution of resistance breaking isolates of the spinach pathogen Peronospora effusa

Peronospora effusa causes downy mildew, the economically most important disease of cultivated spinach worldwide. To date, 19 P. effusa races have been denominated based on their capacity to break spinach resistances, but their genetic diversity and the evolutionary processes that contribute to race emergence are unknown. Here, we performed the first systematic analysis of P. effusa races showing that those emerge by both asexual and sexual reproduction. Specifically, we studied the diversity of 26 P. effusa isolates from 16 denominated races based on mitochondrial and nuclear comparative genomics. Mitochondrial genomes based on long-read sequencing coupled with diversity assessment based on short-read sequencing uncovered two mitochondrial haplogroups, each with distinct genome organization. Nuclear genome-wide comparisons of the 26 isolates revealed that ten isolates from six races could clearly be divided into three asexually evolving groups, in concordance with their mitochondrial phylogeny. The remaining isolates showed signals of reticulated evolution and discordance between nuclear and mitochondrial phylogenies, suggesting that these evolved through sexual reproduction. Increased understanding of this pathogen's reproductive modes will provide the framework for future studies into the molecular mechanisms underlying race emergence and into the P. effusa-spinach interaction, thus assisting in sustainable production of spinach through knowledge-driven resistance breeding.

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Import of Non-Coding RNAs into Human Mitochondria: A Critical Review and Emerging Approaches

Cells ◽

10.3390/cells8030286 ◽

2019 ◽

Vol 8 (3) ◽

pp. 286 ◽

Cited By ~ 15

Author(s):

Damien Jeandard ◽

Anna Smirnova ◽

Ivan Tarassov ◽

Eric Barrey ◽

Alexandre Smirnov ◽

...

Keyword(s):

Molecular Mechanisms ◽

Nuclear Genome ◽

Genetic System ◽

Mitochondrial Import ◽

In Situ Techniques ◽

Genome Wide ◽

Experimental Approaches ◽

Non Coding Rnas ◽

Analyze Data

Mitochondria harbor their own genetic system, yet critically depend on the import of a number of nuclear-encoded macromolecules to ensure their expression. In all eukaryotes, selected non-coding RNAs produced from the nuclear genome are partially redirected into the mitochondria, where they participate in gene expression. Therefore, the mitochondrial RNome represents an intricate mixture of the intrinsic transcriptome and the extrinsic RNA importome. In this review, we summarize and critically analyze data on the nuclear-encoded transcripts detected in human mitochondria and outline the proposed molecular mechanisms of their mitochondrial import. Special attention is given to the various experimental approaches used to study the mitochondrial RNome, including some recently developed genome-wide and in situ techniques.

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Biodiversity genomics of small metazoans: high quality de novo genomes from single specimens of field-collected and ethanol-preserved springtails

10.1101/2020.08.10.244541 ◽

2020 ◽

Cited By ~ 2

Author(s):

Clément Schneider ◽

Christian Woehle ◽

Carola Greve ◽

Cyrille A. D’Haese ◽

Magnus Wolf ◽

...

Keyword(s):

Genome Sequencing ◽

De Novo ◽

Genetic Model ◽

Nuclear Genome ◽

High Quality ◽

Sequencing Technologies ◽

Natural Product Research ◽

Genome Wide ◽

Long Read ◽

Hmw Dna

ABSTRACTGenome sequencing of all known eukaryotes on Earth promises unprecedented advances in evolutionary sciences, ecology, systematics and in biodiversity-related applied fields such as environmental management and natural product research. Advances in DNA sequencing technologies make genome sequencing feasible for many non-genetic model species. However, genome sequencing today relies on large quantities of high quality, high molecular weight (HMW) DNA which is mostly obtained from fresh tissues. This is problematic for biodiversity genomics of Metazoa as most species are small and yield minute amounts of DNA. Furthermore, briging living specimens to the lab bench not realistic for the majority of species.Here we overcome those difficulties by sequencing two species of springtails (Collembola) from single specimens preserved in ethanol. We used a newly developed, genome-wide amplification-based protocol to generate PacBio libraries for HiFi long-read sequencing.The assembled genomes were highly continuous. They can be considered complete as we recovered over 95% of BUSCOs. Genome-wide amplification does not seem to bias genome recovery. Presence of almost complete copies of the mitochondrial genome in the nuclear genome were pitfalls for automatic assemblers. The genomes fit well into an existing phylogeny of springtails. A neotype is designated for one of the species, blending genome sequencing and creation of taxonomic references.Our study shows that it is possible to obtain high quality genomes from small, field-preserved sub-millimeter metazoans, thus making their vast diversity accessible to the fields of genomics.

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MCRiceRepGP: a framework for identification of sexual reproduction associated coding and lincRNA genes in rice

10.1101/271353 ◽

2018 ◽

Author(s):

Agnieszka A. Golicz ◽

Prem L. Bhalla ◽

Mohan B. Singh

Keyword(s):

Machine Learning ◽

Decision Analysis ◽

Sexual Reproduction ◽

Web Application ◽

Molecular Mechanisms ◽

Rice Genome ◽

Protein Coding ◽

Genome Wide ◽

Plant Sexual Reproduction ◽

Global Food

AbstractSexual reproduction in plants underpins global food production and evolution. It is a complex process, requiring intricate signalling pathways integrating a multitude of internal and external cues. However, key players and especially non-coding genes controlling plant sexual reproduction remain elusive. We report the development of MCRiceRepGP a novel machine learning framework, which integrates genomic, transcriptomic, homology and available phenotypic evidence and employs multi-criteria decision analysis and machine learning to predict coding and non-coding genes involved in rice sexual reproduction.The rice genome was re-annotated using deep sequencing transcriptomic data from reproduction-associated tissues/cell types identifying novel putative protein coding genes, transcript isoforms and long intergenic non-coding RNAs (lincRNAs). MCRiceRepGP was used for genome-wide discovery of sexual reproduction associated genes in rice; 2,275 protein-coding and 748 lincRNA genes were predicted to be involved in sexual reproduction. The annotation performed and the genes identified, especially the ones for which mutant lines with phenotypes are available provide a valuable resource. The analysis of genes identified gives insights into the genetic architecture of plant sexual reproduction. MCRiceRepGP can be used in combination with other genome-wide studies, like GWAS, giving more confidence that the genes identified are associated with the biological process of interest. As more data, especially about mutant plant phenotypes will become available, the power of MCRiceRepGP with grow providing researchers with a tool to identify candidate genes for future experiments. MCRiceRepGP is available as a web application (http://mcgplannotator.com/MCRiceRepGP/)Significance statementRice is a staple food crop plant for over half of the world’s population and sexual reproduction resulting in grain formation is a key process underpinning global food security. Despite considerable research efforts, much remains to be learned about the molecular mechanisms involved in rice sexual reproduction. We have developed MCRiceRepGP, a novel framework which allows prediction of sexual reproduction associated genes using multi-omics data, multicriteria decision analysis and machine learning. The genes identified and the methodology developed will become a significant resource for the plant research community.

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Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells

10.1101/756056 ◽

2019 ◽

Author(s):

Ryuichiro Nakato ◽

Youichiro Wada ◽

Ryo Nakaki ◽

Genta Nagae ◽

Yuki Katou ◽

...

Keyword(s):

Endothelial Cells ◽

Molecular Mechanisms ◽

Hox Genes ◽

Vascular System ◽

Vascular Endothelial Cells ◽

Chromatin Interaction ◽

Marker Genes ◽

Systematic Analysis ◽

Genome Wide ◽

Extracellular Stimuli

ABSTRACTBackgroundEndothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood.ResultsTo characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We identified 3,765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. Notably, reflecting the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing.ConclusionsWhile the importance of several HOX genes for early vascular development and adult angiogenesis in pathological conditions has been reported, a systematic analysis of the regulation and roles of HOX genes in mature tissue cells has been lacking. These datasets provide a valuable resource for understanding the vascular system and associated diseases.

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Artificial Intelligence for epigenetics: towards personalized medicine

Current Medicinal Chemistry ◽

10.2174/0929867327666201117142006 ◽

2020 ◽

Vol 27 ◽

Author(s):

Giulia De Riso ◽

Sergio Cocozza

Keyword(s):

Biological Sciences ◽

Artificial Intelligence ◽

Personalized Medicine ◽

Molecular Mechanisms ◽

Genomic Sequence ◽

Health Care Interventions ◽

Genome Wide ◽

Genetic And Environmental Factors ◽

Opening Up ◽

Omic Data

: Epigenetics is a field of biological sciences focused on the study of reversible, heritable changes in gene function not due to modifications of the genomic sequence. These changes are the result of a complex cross-talk between several molecular mechanisms, that is in turn orchestrated by genetic and environmental factors. The epigenetic profile captures the unique regulatory landscape and the exposure to environmental stimuli of an individual. It thus constitutes a valuable reservoir of information for personalized medicine, which is aimed at customizing health-care interventions based on the unique characteristics of each individual. Nowadays, the complex milieu of epigenomic marks can be studied at the genome-wide level thanks to massive, highthroughput technologies. This new experimental approach is opening up new and interesting knowledge perspectives. However, the analysis of these complex omic data requires to face important analytic issues. Artificial Intelligence, and in particular Machine Learning, are emerging as powerful resources to decipher epigenomic data. In this review, we will first describe the most used ML approaches in epigenomics. We then will recapitulate some of the recent applications of ML to epigenomic analysis. Finally, we will provide some examples of how the ML approach to epigenetic data can be useful for personalized medicine.

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Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types

Science Advances ◽

10.1126/sciadv.abd9036 ◽

2021 ◽

Vol 7 (3) ◽

pp. eabd9036

Author(s):

Sara Saez-Atienzar ◽

Sara Bandres-Ciga ◽

Rebekah G. Langston ◽

Jonggeol J. Kim ◽

Shing Wan Choi ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Membrane Trafficking ◽

Molecular Mechanisms ◽

Cell Types ◽

Polygenic Risk Score ◽

Genome Wide ◽

Genome Wide Data ◽

Data Driven Approach ◽

Single Nucleus ◽

Lateral Sclerosis

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.

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Nuclear genome-wide associations with mitochondrial heteroplasmy

Science Advances ◽

10.1126/sciadv.abe7520 ◽

2021 ◽

Vol 7 (12) ◽

pp. eabe7520

Author(s):

Priyanka Nandakumar ◽

Chao Tian ◽

Jared O’Connell ◽

David Hinds ◽

Andrew D. Paterson ◽

...

Keyword(s):

Nuclear Genome ◽

Multiple Roles ◽

European Ancestry ◽

Mitochondrial Transcription Factor ◽

Genome Wide ◽

Mtdna Sequence ◽

Nuclear Component ◽

Mitochondrial Transcription Factor A ◽

Mitochondrial Heteroplasmy ◽

The Stability

The role of the nuclear genome in maintaining the stability of the mitochondrial genome (mtDNA) is incompletely known. mtDNA sequence variants can exist in a state of heteroplasmy, which denotes the coexistence of organellar genomes with different sequences. Heteroplasmic variants that impair mitochondrial capacity cause disease, and the state of heteroplasmy itself is deleterious. However, mitochondrial heteroplasmy may provide an intermediate state in the emergence of novel mitochondrial haplogroups. We used genome-wide genotyping data from 982,072 European ancestry individuals to evaluate variation in mitochondrial heteroplasmy and to identify the regions of the nuclear genome that affect it. Age, sex, and mitochondrial haplogroup were associated with the extent of heteroplasmy. GWAS identified 20 loci for heteroplasmy that exceeded genome-wide significance. This included a region overlapping mitochondrial transcription factor A (TFAM), which has multiple roles in mtDNA packaging, replication, and transcription. These results show that mitochondrial heteroplasmy has a heritable nuclear component.

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Genome-Wide Mapping of Histone H3 Lysine 4 Trimethylation (H3K4me3) and Its Involvement in Fatty Acid Biosynthesis in Sunflower Developing Seeds

Plants ◽

10.3390/plants10040706 ◽

2021 ◽

Vol 10 (4) ◽

pp. 706

Author(s):

Antonio J. Moreno-Pérez ◽

Raquel Martins-Noguerol ◽

Cristina DeAndrés-Gil ◽

Mónica Venegas-Calerón ◽

Rosario Sánchez ◽

...

Keyword(s):

Fatty Acid ◽

Chromatin Remodeling ◽

Molecular Mechanisms ◽

Acid Metabolism ◽

Fatty Acid Biosynthesis ◽

Acid Synthesis ◽

Sunflower Seeds ◽

Acid Biosynthesis ◽

Functional Regions ◽

Genome Wide

Histone modifications are of paramount importance during plant development. Investigating chromatin remodeling in developing oilseeds sheds light on the molecular mechanisms controlling fatty acid metabolism and facilitates the identification of new functional regions in oil crop genomes. The present study characterizes the epigenetic modifications H3K4me3 in relationship with the expression of fatty acid-related genes and transcription factors in developing sunflower seeds. Two master transcriptional regulators identified in this analysis, VIV1 (homologous to Arabidopsis ABI3) and FUS3, cooperate in the regulation of WRINKLED 1, a transcriptional factor regulating glycolysis, and fatty acid synthesis in developing oilseeds.

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Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

Scientific Reports ◽

10.1038/s41598-021-85871-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Helena R. R. Wells ◽

Fatin N. Zainul Abidin ◽

Maxim B. Freidin ◽

Frances M. K. Williams ◽

Sally J. Dawson

Keyword(s):

Association Study ◽

Molecular Mechanisms ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Uk Biobank ◽

Significance Threshold ◽

Genome Wide ◽

Final Sample ◽

Close Proximity ◽

Repressor Complex

AbstractTinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case–control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E−08), rs4900545 (p = 1.8E−08) and 14:103042287_CT_C (p = 3.50E−08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E−06.

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