Genetic Diversity in Yeast Assessed With Whole-Genome Oligonucleotide Arrays

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Elizabeth A Winzeler ◽  
Cristian I Castillo-Davis ◽  
Guy Oshiro ◽  
David Liang ◽  
Daniel R Richards ◽  
...  
Keyword(s):  
Wide Distribution ◽  
Oligonucleotide Arrays ◽  
Gene Deletions ◽  
Genome Variability ◽  
Yeast Strains ◽  
Genome Wide ◽  
Single Feature ◽  
Central Regions ◽  
Intraspecies Variability ◽  
Common Laboratory

Abstract The availability of a complete genome sequence allows the detailed study of intraspecies variability. Here we use high-density oligonucleotide arrays to discover 11,115 single-feature polymorphisms (SFPs) existing in one or more of 14 different yeast strains. We use these SFPs to define regions of genetic identity between common laboratory strains of yeast. We assess the genome-wide distribution of genetic variation on the basis of this yeast population. We find that genome variability is biased toward the ends of chromosomes and is more likely to be found in genes with roles in fermentation or in transport. This subtelomeric bias may arise through recombination between nonhomologous sequences because full-gene deletions are more common in these regions than in more central regions of the chromosome.

scholarly journals A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia

2017 ◽  
Vol 7 (7) ◽  
pp. 2171-2184 ◽  
Author(s):  
Jordi Leno-Colorado ◽  
Nick J Hudson ◽  
Antonio Reverter ◽  
Miguel Pérez-Enciso
Keyword(s):  
Statistical Significance ◽  
Purifying Selection ◽  
Wide Distribution ◽  
Physiological Basis ◽  
Genome Variability ◽  
Genome Wide ◽  
Biological Interpretation ◽  
The Impact ◽  
The Brain ◽  
Different Levels

Abstract Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig (Sus scrofa) is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst) and linkage disequilibrium (nSL) statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q-value < 0.05 in Asia and Europe, respectively; five were shared across continents. In Asia, we found six significant pathways related to behavior, which involved essential neurotransmitters like dopamine and serotonin. Several significant pathways were interrelated and shared a variable percentage of genes. There were 12 genes present in >10 significant pathways (in terms of Fst), comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis), a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other physiological and developmental processes.

scholarly journals Author Correction: Determinants of genome-wide distribution and evolution of uORFs in eukaryotes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hong Zhang ◽  
Yirong Wang ◽  
Xinkai Wu ◽  
Xiaolu Tang ◽  
Changcheng Wu ◽  
...  
Keyword(s):  
Wide Distribution ◽  
Genome Wide

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22435-2

scholarly journals Genome-wide distribution of DNA replication origins at A+T-rich islands in Schizosaccharomyces pombe

EMBO Reports ◽  
2003 ◽  
Vol 4 (11) ◽  
pp. 1048-1053 ◽  
Author(s):  
Mónica Segurado ◽  
Alberto de Luis ◽  
Francisco Antequera
Keyword(s):  
Dna Replication ◽  
Schizosaccharomyces Pombe ◽  
Wide Distribution ◽  
Replication Origins ◽  
Genome Wide ◽  
Dna Replication Origins

scholarly journals Genome-wide association studies: assessing trait characteristics in model and crop plants

2021 ◽  
Author(s):  
Saleh Alseekh ◽  
Dimitrina Kostova ◽  
Mustafa Bulut ◽  
Alisdair R. Fernie
Keyword(s):  
Biotic Resistance ◽  
Association Studies ◽  
Critical Evaluation ◽  
Genome Wide Association ◽  
Functional Study ◽  
Genome Wide Association Studies ◽  
Future Perspectives ◽  
Crop Species ◽  
Genome Wide ◽  
Single Feature

AbstractGWAS involves testing genetic variants across the genomes of many individuals of a population to identify genotype–phenotype association. It was initially developed and has proven highly successful in human disease genetics. In plants genome-wide association studies (GWAS) initially focused on single feature polymorphism and recombination and linkage disequilibrium but has now been embraced by a plethora of different disciplines with several thousand studies being published in model and crop species within the last decade or so. Here we will provide a comprehensive review of these studies providing cases studies on biotic resistance, abiotic tolerance, yield associated traits, and metabolic composition. We also detail current strategies of candidate gene validation as well as the functional study of haplotypes. Furthermore, we provide a critical evaluation of the GWAS strategy and its alternatives as well as future perspectives that are emerging with the emergence of pan-genomic datasets.

scholarly journals Epigenetic mechanisms in sexual differentiation of the brain and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Wide Distribution ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
The Brain

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.

scholarly journals Delineation of the Ancestral Tus-Dependent Replication Fork Trap

2021 ◽  
Author(s):  
Casey Toft ◽  
Morgane Moreau ◽  
Jiri Perutka ◽  
Savitri Mandapati ◽  
Peter Enyeart ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Replication Fork ◽  
Wide Distribution ◽  
Replication Forks ◽  
Genome Wide ◽  
Replication Fork Arrest

In Escherichia coli, DNA replication termination is orchestrated by two clusters of Ter sites forming a DNA replication fork trap when bound by Tus proteins. The formation of a ‘locked’ Tus-Ter complex is essential for halting incoming DNA replication forks. However, the absence of replication fork arrest at some Ter sites raised questions about their significance. In this study, we examined the genome-wide distribution of Tus and found that only the six innermost Ter sites (TerA-E and G) were significantly bound by Tus. We also found that a single ectopic insertion of TerB in its non-permissive orientation could not be achieved, advocating against a need for ‘back-up’ Ter sites. Finally, examination of the genomes of a variety of Enterobacterales revealed a new replication fork trap architecture mostly found outside the Enterobacteriaceae family. Taken together, our data enabled the delineation of a narrow ancestral Tus-dependent DNA replication fork trap consisting of only two Ter sites.

scholarly journals MtrA regulation of essential peptidoglycan cleavage in Mycobacterium tuberculosis during infection

2021 ◽  
Author(s):  
Eliza J. R. Peterson ◽  
Aaron N Brooks ◽  
David J. Reiss ◽  
Amardeep Kaur ◽  
Wei-Ju Wu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Regulatory Elements ◽  
Wide Distribution ◽  
Regulatory Control ◽  
Transcriptional Responses ◽  
Pathogenic Organism ◽  
Rifampicin Treatment ◽  
Genome Wide ◽  
Gene Regulatory Elements ◽  
Dynamic Interplay

AbstractThe success of Mycobacterium tuberculosis (Mtb) is largely due to its ability to withstand multiple stresses encountered in the host. Here, we present a data-driven model that captures the dynamic interplay of environmental cues and genome-encoded regulatory programs in Mtb. The model captures the genome-wide distribution of cis-acting gene regulatory elements and the conditional influences of transcription factors at those elements to elicit environment-specific responses. Analysis of transcriptional responses that may be essential for Mtb to survive acidic stress within the maturing macrophage, identified regulatory control by the MtrAB two-component signal system. Using genome-wide transcriptomics as well as imaging studies, we have characterized the MtrAB circuit by tunable CRISPRi knockdown in both Mtb and the non-pathogenic organism, M. smegmatis (Msm). These experiments validated the essentiality of MtrA in Mtb, but not Msm. We identified that MtrA regulates multiple enzymes that cleave cell wall peptidoglycan and is required for efficient cell division. Moreover, our results suggest that peptidoglycan cleavage, regulated by MtrA, is necessary for Mtb to survive intracellular stress. Further, we present MtrA as an attractive drug target, as even weak repression of mtrA results in loss of Mtb viability and completely clears the bacteria with low-dose isoniazid or rifampicin treatment.

scholarly journals Genome-Wide Screening and Genetic Networks in Pleiotropic Drug Resistance, Oxidative Stress, and Drug Targets in S. Cerevisiae

2021 ◽  
Author(s):  
◽  
Ploi Yibmantasiri
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Abc Transporters ◽  
Oxidative Stress Response ◽  
Genetic Networks ◽  
Antifungal Compound ◽  
Pleiotropic Drug Resistance ◽  
Gene Deletions ◽  
Genome Wide ◽  
And Oxidative Stress

<p>One of the major problems in biology is to identify genes that are involved in specific processes. Classical genetics and biochemistry, although powerful and informative, can be very labour intensive and do not necessarily characterise networked genes in processes that may overarch numerous biochemical pathways. Here we utilised genomic tools that are capable of defining networks to identify genes involved the complex target mode-of-action of a novel antifungal compound, neothyonidioside and in regulating specific stress processes and the PDR phenotype. The first part of this study investigated the mode-of-action of the antifungal compound, neothyonidioside (neo). We developed a neo resistant mutant strain then utilising a modification of SGAM, a genetic mapping tool, and application of genome-wide chemical-genetic profiling, we identified the neo resistant locus NCP1. This gene acts at a late step in ergosterol biosynthesis but is not the target of neo. The finding that many of the component genes in the ESCRT complex were necessary for neo resistance allowed us to predict and verify by high-content fluorescence microcopy that interruptions in the endosome-multivesicular body pathway were involved. From the known function of the ESCRT proteins and that neo binds ergosterol only above threshold concentrations of ergosterol (explaining the mutant phenotype) we concluded that neo disruption of membrane curvature and fusion capability in the endosome-vacuole pathway is its target. In the second part of this study we identified genes in a genome-wide fashion that modulate the pleiotropic drug resistance (PDR) phenotype and oxidative stress response. Many PDR targets are well studied ABC transporters (e.g. PDR5 , YOR1), but the modulating events between xenobiotic sensing and transcription factor activation, and possible crosstalk between PDR and other stress responses such as oxidative stress are not well characterised. To identify specific genes involved in the PDR and oxidative stress processes, we developed a fluorescent reporter screen for effects on the PDR-target ABC-transporters, Pdr5p and Yor1p tagged with GFP. For the oxidative stress response, the oxidative stress (OS) transcription factor Yap1p tagged with GFP was used. Each reporter was placed in the yeast non-essential gene deletion background of ~4800 strains which were then subjected to either xenobiotic treatments (PDR –GFP reporters) or oxidant treatments (Yap1p-GFP). We then screened for gene deletions which prevented the normal upregulation of PDR reporters in the presence of xenobiotics. Controls were included in the screens that assured we were assessing genes that must contribute to or act before the transcription of the ABC-transporters. A similar screening strategy was pursued for identifying gene deletions that prevent the normal nuclear re-localisation of Yap1p in the presence of oxidants. A major finding in this study was identification of genes contributing to the PDR phenotype that involved signalling (Rho-GTPase, MAPK), that were involved in RNA polymerase II mediator complexes and chromatin modification (subunits of ADA and SAGA histone acetyltransferase complexes), and that were involved in sphingo/phosphorlipids biosynthesis. Secondary screens comprising spot dilution growth assays and Western blots of Pdr5p abundance confirmed key genes of the primary screen and showed that these were specific and not global transcriptional effects.For some of the gene-dependencies, our results can only be construed to indicate the existence of alternative pathways underpinning the PDR phenotype in a Pdr1p/Pdr3p independent manner. We then supposed that if in fact PDR phenotypes are the result of genetic networks, then genes known to interact with the most highly connected hubs from our PDR screen results should also to some extent contribute to the PDR phenotype (spot dilution growth assays, Western blot abundance). A selection of 18 such genes that also appeared in our primary screen but were deemed to be below the cut-off point were phenotype tested and in 60% of the cases showed similar phenotypes to the genes already identified. This result not only proved the validity of the screening methods but validated the original supposition, i.e. that PDR phenotypes can be affected, through gene networks.</p>

scholarly journals Restricted nucleation and piRNA-mediated establishment of heterochromatin during embryogenesis in Drosophila miranda

2021 ◽  
Author(s):  
Kevin H.-C. Wei ◽  
Carolus Chan ◽  
Doris Bachtrog
Keyword(s):  
Genome Stability ◽  
Repetitive Sequences ◽  
Developmental Time ◽  
Wide Distribution ◽  
Promoter Regions ◽  
Architectural Feature ◽  
Genome Wide ◽  
Nucleation Sites ◽  
Zygotic Transcription ◽  
Initial Nucleation

Heterochromatin is a key architectural feature of eukaryotic genomes, crucial for silencing of repetitive elements and maintaining genome stability. Heterochromatin shows stereotypical enrichment patterns around centromeres and repetitive sequences, but the molecular details of how heterochromatin is established during embryogenesis are poorly understood. Here, we map the genome-wide distribution of H3K9me3-dependent heterochromatin in individual embryos of D. miranda at precisely staged developmental time points. We find that canonical H3K9me3 enrichment patterns are established early on before cellularization, and mature into stable and broad heterochromatin domains through development. Intriguingly, initial nucleation sites of H3K9me3 enrichment appear as early as embryonic stage3 (nuclear cycle 9) over transposable elements (TE) and progressively broaden, consistent with spreading to neighboring nucleosomes. The earliest nucleation sites are limited to specific regions of a small number of TE families and often appear over promoter regions, while late nucleation develops broadly across most TEs. Early nucleating TEs are highly targeted by maternal piRNAs and show early zygotic transcription, consistent with a model of co-transcriptional silencing of TEs by small RNAs. Interestingly, truncated TE insertions lacking nucleation sites show significantly reduced enrichment across development, suggesting that the underlying sequences play an important role in recruiting histone methyltransferases for heterochromatin establishment.

Sign in / Sign up

Export Citation Format

Share Document