Implications of the Evolutionary Trajectory of Centromeres in the Fungal Kingdom

2020 ◽  
Vol 74 (1) ◽  
pp. 835-853
Author(s):  
Krishnendu Guin ◽  
Lakshmi Sreekumar ◽  
Kaustuv Sanyal
Keyword(s):  
Chromosome Segregation ◽  
Fungal Species ◽  
Last Common Ancestor ◽  
Yeast Saccharomyces Cerevisiae ◽  
Evolutionary Trajectory ◽  
Centromeric Chromatin ◽  
Evolutionarily Conserved ◽  
Sequence Elements ◽  
Fundamental Biological Process ◽  
Fungal Kingdom

Chromosome segregation during the cell cycle is an evolutionarily conserved, fundamental biological process. Dynamic interaction between spindle microtubules and the kinetochore complex that assembles on centromere DNA is required for faithful chromosome segregation. The first artificial minichromosome was constructed by cloning the centromere DNA of the budding yeast Saccharomyces cerevisiae. Since then, centromeres have been identified in >60 fungal species. The DNA sequence and organization of the sequence elements are highly diverse across these fungal centromeres. In this article, we provide a comprehensive view of the evolution of fungal centromeres. Studies of this process facilitated the identification of factors influencing centromere specification, maintenance, and propagation through many generations. Additionally, we discuss the unique features and plasticity of centromeric chromatin and the involvement of centromeres in karyotype evolution. Finally, we discuss the implications of recurrent loss of RNA interference (RNAi) and/or heterochromatin components on the trajectory of the evolution of fungal centromeres and propose the centromere structure of the last common ancestor of three major fungal phyla—Ascomycota, Basidiomycota, and Mucoromycota.

scholarly journals Polo kinase Cdc5 associates with centromeres to facilitate the removal of centromeric cohesin during mitosis

2016 ◽  
Vol 27 (14) ◽  
pp. 2286-2300 ◽  
Author(s):  
Prashant K. Mishra ◽  
Sultan Ciftci-Yilmaz ◽  
David Reynolds ◽  
Wei-Chun Au ◽  
Lars Boeckmann ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Centromeric Chromatin ◽  
Polo Kinase ◽  
Chromatid Cohesion ◽  
Evolutionarily Conserved ◽  
Sister Chromatid Separation

Sister chromatid cohesion is essential for tension-sensing mechanisms that monitor bipolar attachment of replicated chromatids in metaphase. Cohesion is mediated by the association of cohesins along the length of sister chromatid arms. In contrast, centromeric cohesin generates intrastrand cohesion and sister centromeres, while highly cohesin enriched, are separated by >800 nm at metaphase in yeast. Removal of cohesin is necessary for sister chromatid separation during anaphase, and this is regulated by evolutionarily conserved polo-like kinase (Cdc5 in yeast, Plk1 in humans). Here we address how high levels of cohesins at centromeric chromatin are removed. Cdc5 associates with centromeric chromatin and cohesin-associated regions. Maximum enrichment of Cdc5 in centromeric chromatin occurs during the metaphase-to-anaphase transition and coincides with the removal of chromosome-associated cohesin. Cdc5 interacts with cohesin in vivo, and cohesin is required for association of Cdc5 at centromeric chromatin. Cohesin removal from centromeric chromatin requires Cdc5 but removal at distal chromosomal arm sites does not. Our results define a novel role for Cdc5 in regulating removal of centromeric cohesins and faithful chromosome segregation.

scholarly journals Early diverging fungus Mucor circinelloides lacks centromeric histone CENP-A and displays a mosaic of point and regional centromeres

2019 ◽  
Author(s):  
María Isabel Navarro-Mendoza ◽  
Carlos Pérez-Arques ◽  
Shweta Panchal ◽  
Francisco E. Nicolás ◽  
Stephen J. Mondo ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Critical Role ◽  
Mucor Circinelloides ◽  
Rnai Pathway ◽  
Holocentric Chromosomes ◽  
Hybrid Features ◽  
Retrotransposable Element ◽  
Evolutionarily Conserved ◽  
Opportunistic Human Pathogen ◽  
Fungal Kingdom

AbstractCentromeres are rapidly evolving across eukaryotes, despite performing a conserved function to ensure high fidelity chromosome segregation. CENP-A chromatin is a hallmark of a functional centromere in most organisms. Due to its critical role in kinetochore architecture, the loss of CENP-A is tolerated in only a few organisms, many of which possess holocentric chromosomes. Here, we characterize the consequence of the loss of CENP-A in the fungal kingdom. Mucor circinelloides, an opportunistic human pathogen, lacks CENP-A along with the evolutionarily conserved CENP-C, but assembles a monocentric chromosome with a localized kinetochore complex throughout the cell cycle. Mis12 and Dsn1, two conserved kinetochore proteins were found to bind nine short overlapping regions, each comprising an ∼200-bp AT-rich sequence followed by a centromere-specific conserved motif that echoes the structure of budding yeast point centromeres. Resembling fungal regional centromeres, these core centromere regions are embedded in large genomic expanses devoid of genes yet marked by Grem-LINE1s, a novel retrotransposable element silenced by the Dicer-dependent RNAi pathway. Our results suggest that these hybrid features of point and regional centromeres arose from the absence of CENP-A, thus defining novel mosaic centromeres in this early-diverging fungus.

scholarly journals New Method for Identifying Fungal Kingdom Enzyme Hotspots from Genome Sequences

2021 ◽  
Vol 7 (3) ◽  
pp. 207
Author(s):  
Lene Lange ◽  
Kristian Barrett ◽  
Anne S. Meyer
Keyword(s):  
Fungal Species ◽  
Fungal Genome ◽  
Sequencing Data ◽  
Carbohydrate Active Enzymes ◽  
New Approach ◽  
Fungal Enzyme ◽  
Biomass Processing ◽  
Fungal Genomes ◽  
Robust Prediction ◽  
Fungal Kingdom

Fungal genome sequencing data represent an enormous pool of information for enzyme discovery. Here, we report a new approach to identify and quantitatively compare biomass-degrading capacity and diversity of fungal genomes via integrated function-family annotation of carbohydrate-active enzymes (CAZymes) encoded by the genomes. Based on analyses of 1932 fungal genomes the most potent hotspots of fungal biomass processing CAZymes are identified and ranked according to substrate degradation capacity. The analysis is achieved by a new bioinformatics approach, Conserved Unique Peptide Patterns (CUPP), providing for CAZyme-family annotation and robust prediction of molecular function followed by conversion of the CUPP output to lists of integrated “Function;Family” (e.g., EC 3.2.1.4;GH5) enzyme observations. An EC-function found in several protein families counts as different observations. Summing up such observations allows for ranking of all analyzed genome sequenced fungal species according to richness in CAZyme function diversity and degrading capacity. Identifying fungal CAZyme hotspots provides for identification of fungal species richest in cellulolytic, xylanolytic, pectinolytic, and lignin modifying enzymes. The fungal enzyme hotspots are found in fungi having very different lifestyle, ecology, physiology and substrate/host affinity. Surprisingly, most CAZyme hotspots are found in enzymatically understudied and unexploited species. In contrast, the most well-known fungal enzyme producers, from where many industrially exploited enzymes are derived, are ranking unexpectedly low. The results contribute to elucidating the evolution of fungal substrate-digestive CAZyme profiles, ecophysiology, and habitat adaptations, and expand the knowledge base for novel and improved biomass resource utilization.

scholarly journals Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 901 ◽  
Author(s):  
Asiya Gusa ◽  
Sue Jinks-Robertson
Keyword(s):  
Fungal Pathogens ◽  
Repetitive Sequences ◽  
Pathogenic Fungi ◽  
Genetic Alterations ◽  
Fungal Species ◽  
Chronic Infections ◽  
Yeast Saccharomyces Cerevisiae ◽  
Genomic Changes ◽  
Break Site ◽  
Repair Mechanisms

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast Saccharomyces cerevisiae. The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens Candida albicans and Cryptococcus neoformans.

scholarly journals Genes Involved in Sister Chromatid Separation and Segregation in the Budding Yeast Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 453-470
Author(s):  
Sue Biggins ◽  
Needhi Bhalla ◽  
Amy Chang ◽  
Dana L Smith ◽  
Andrew W Murray
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Budding Yeast ◽  
Temperature Sensitive ◽  
Chromosome Behavior ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sister Chromatids ◽  
Marked Chromosome ◽  
Sister Chromatid Separation

Abstract Accurate chromosome segregation requires the precise coordination of events during the cell cycle. Replicated sister chromatids are held together while they are properly attached to and aligned by the mitotic spindle at metaphase. At anaphase, the links between sisters must be promptly dissolved to allow the mitotic spindle to rapidly separate them to opposite poles. To isolate genes involved in chromosome behavior during mitosis, we microscopically screened a temperature-sensitive collection of budding yeast mutants that contain a GFP-marked chromosome. Nine LOC (loss of cohesion) complementation groups that do not segregate sister chromatids at anaphase were identified. We cloned the corresponding genes and performed secondary tests to determine their function in chromosome behavior. We determined that three LOC genes, PDS1, ESP1, and YCS4, are required for sister chromatid separation and three other LOC genes, CSE4, IPL1, and SMT3, are required for chromosome segregation. We isolated alleles of two genes involved in splicing, PRP16 and PRP19, which impair α-tubulin synthesis thus preventing spindle assembly, as well as an allele of CDC7 that is defective in DNA replication. We also report an initial characterization of phenotypes associated with the SMT3/SUMO gene and the isolation of WSS1, a high-copy smt3 suppressor.

In vivo analysis of the Saccharomyces cerevisiae centromere CDEIII sequence: requirements for mitotic chromosome segregation

1991 ◽  
Vol 11 (10) ◽  
pp. 5212-5221
Author(s):  
B Jehn ◽  
R Niedenthal ◽  
J H Hegemann
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Chromosome Segregation ◽  
Artificial Chromosome ◽  
Complete Information ◽  
Saturation Mutagenesis ◽  
Chromosome Loss ◽  
Single Mutation ◽  
Yeast Saccharomyces Cerevisiae ◽  
Double Base

In the yeast Saccharomyces cerevisiae, the complete information needed in cis to specify a fully functional mitotic and meiotic centromere is contained within 120 bp arranged in the three conserved centromeric (CEN) DNA elements CDEI, -II, and -III. The 25-bp CDEIII is most important for faithful chromosome segregation. We have constructed single- and double-base substitutions in all highly conserved residues and one nonconserved residue of this element and analyzed the mitotic in vivo function of the mutated CEN DNAs, using an artificial chromosome. The effects of the mutations on chromosome segregation vary between wild-type-like activity (chromosome loss rate of 4.8 x 10(-4)) and a complete loss of CEN function. Data obtained by saturation mutagenesis of the palindromic core sequence suggest asymmetric involvement of the palindromic half-sites in mitotic CEN function. The poor CEN activity of certain single mutations could be improved by introducing an additional single mutation. These second-site suppressors can be found at conserved and nonconserved positions in CDEIII. Our suppression data are discussed in the context of natural CDEIII sequence variations found in the CEN sequences of different yeast chromosomes.

scholarly journals Phosphorylation of Drosophila CENP-A on serine 20 regulates protein turn-over and centromere-specific loading

2019 ◽  
Vol 47 (20) ◽  
pp. 10754-10770 ◽  
Author(s):  
Anming Huang ◽  
Leopold Kremser ◽  
Fabian Schuler ◽  
Doris Wilflingseder ◽  
Herbert Lindner ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Posttranslational Modifications ◽  
Centromeric Chromatin ◽  
Phosphorylated Form ◽  
Specific Loading ◽  
Histone H3 Variant ◽  
Proteasome Pathway ◽  
Turn Over ◽  
Fine Tune

Abstract Centromeres are specialized chromosomal regions epigenetically defined by the presence of the histone H3 variant CENP-A. CENP-A is required for kinetochore formation which is essential for chromosome segregation during mitosis. Spatial restriction of CENP-A to the centromere is tightly controlled. Its overexpression results in ectopic incorporation and the formation of potentially deleterious neocentromeres in yeast, flies and in various human cancers. While the contribution of posttranslational modifications of CENP-A to these processes has been studied in yeast and mammals to some extent, very little is known about Drosophila melanogaster. Here, we show that CENP-A is phosphorylated at serine 20 (S20) by casein kinase II and that in mitotic cells, the phosphorylated form is enriched on chromatin. Importantly, our results reveal that S20 phosphorylation regulates the turn-over of prenucleosomal CENP-A by the SCFPpa-proteasome pathway and that phosphorylation promotes removal of CENP-A from ectopic but not from centromeric sites in chromatin. We provide multiple lines of evidence for a crucial role of S20 phosphorylation in controlling restricted incorporation of CENP-A into centromeric chromatin in flies. Modulation of the phosphorylation state of S20 may provide the cells with a means to fine-tune CENP-A levels in order to prevent deleterious loading to extra-centromeric sites.

scholarly journals Integrative transcriptome analysis discloses the molecular basis of a heterogeneous fungal phytopathogen complex, Rhizoctonia solani AG-1 subgroups

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Naoki Yamamoto ◽  
Yanran Wang ◽  
Runmao Lin ◽  
Yueyang Liang ◽  
Yao Liu ◽  
...  
Keyword(s):  
Rhizoctonia Solani ◽  
Transcriptome Analysis ◽  
Molecular Basis ◽  
Ethylene Biosynthesis ◽  
Fungal Species ◽  
Detoxification Enzymes ◽  
Secreted Proteins ◽  
Evolutionary Trajectory ◽  
Pathogenic Factors ◽  
Allergen Protein

AbstractRhizoctonia solani is a fungal species complex that causes necrotrophic crop diseases. It comprises several anastomosis groups, some of which include intra-subgroups, such as AG-1 IA and AG-1 IB, exhibiting varying pathogenicity. Owing to its heterozygous and multinucleate features, genomic analyses of R. solani are still challenging, and understanding of its genetic diversity and genic components is limited. In this study, in order to elucidate the molecular basis of this phytopathogen complex, an integrated transcriptome analysis was undertaken for three subgroups of AG-1, i.e. AG-1 IA, AG-1 IB, and AG-1 IC. Sequence variations suggested substantial evolutionary distances within AG-1. Transcript simple sequence repeats showed comparable characteristics among AG-1, but contained polymorphic sites. Intra-subgroup polymorphisms suggested varying genic heterozygosity within AG-1, suggesting their independent evolutionary trajectory. Sequences of pathogenic factors, phytotoxin biosynthesis pathway enzymes, secreted lignocellulosic enzymes, secreted reactive oxygen species detoxification enzymes, apoplastic/cytoplasmic effector candidates, were conserved among those subgroups. dN/dS ratios of a secretome subset suggested core secreted proteins in AG-1 and distinct evolution of Cys-rich small secreted proteins after differentiation of AG-1 subgroups. Identification of likely pathogenic factors including allergen protein homologues, oxidative phosphorylation and ethylene biosynthesis pathways, and diversification of polysaccharide monooxygenases provides molecular insight into key genomic components that play a role in R. solani pathogenesis.

scholarly journals Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5.

1996 ◽  
Vol 16 (2) ◽  
pp. 593-602 ◽  
Author(s):  
R Candau ◽  
P A Moore ◽  
L Wang ◽  
N Barlev ◽  
C Y Ying ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Sequence Similarity ◽  
Adaptor Proteins ◽  
Yeast Two Hybrid ◽  
Yeast Saccharomyces Cerevisiae ◽  
Activation Domains ◽  
Evolutionarily Conserved ◽  
Human Proteins ◽  
Two Hybrid

Transcriptional adaptor proteins are required for full function of higher eukaryotic acidic activators in the yeast Saccharomyces cerevisiae, suggesting that this pathway of activation is evolutionarily conserved. Consistent with this view, we have identified possible human homologs of yeast ADA2 (yADA2) and yeast GCN5 (yGCN5), components of a putative adaptor complex. While there is overall sequence similarity between the yeast and human proteins, perhaps more significant is conservation of key sequence features with other known adaptors. We show several functional similarities between the human and yeast adaptors. First, as shown for yADA2 and yGCN5, human ADA2 (hADA2) and human GCN5 (hGCN5) interacted in vivo in a yeast two-hybrid assay. Moreover, hGCN5 interacted with yADA2 in this assay, suggesting that the human proteins form similar complexes. Second, both yADA2 and hADA2 contain cryptic activation domains. Third, hGCN5 and yGCN5 had similar stabilizing effects on yADA2 in vivo. Furthermore, the region of yADA2 that interacted with yGCN5 mapped to the amino terminus of yADA2, which is highly conserved in hADA2. Most striking, is the behavior of the human proteins in human cells. First, GAL4-hADA2 activated transcription in HeLa cells, and second, either hADA2 or hGCN5 augmented GAL4-VP16 activation. These data indicated that the human proteins correspond to functional homologs of the yeast adaptors, suggesting that these cofactors play a key role in transcriptional activation.

scholarly journals Regional centromeres in the yeastCandida lusitaniaelack pericentromeric heterochromatin

2015 ◽  
Vol 112 (39) ◽  
pp. 12139-12144 ◽  
Author(s):  
Shivali Kapoor ◽  
Lisha Zhu ◽  
Cara Froyd ◽  
Tao Liu ◽  
Laura N. Rusche
Keyword(s):  
Chromosome Segregation ◽  
Consensus Sequence ◽  
Distinct Type ◽  
Distinct Pattern ◽  
Pericentromeric Heterochromatin ◽  
Centromeric Chromatin ◽  
Chip Sequencing ◽  
Conserved Sequence ◽  
Centromere Proteins ◽  
Candida Lusitaniae

Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional centromeres require pericentromeric heterochromatin. In the yeastCandida lusitaniae, we identified a distinct type of regional centromere that lacks pericentromeric heterochromatin. Centromere locations were determined by ChIP-sequencing of two key centromere proteins, Cse4 and Mif2, and are consistent with bioinformatic predictions. The centromeric DNA sequence was unique for each chromosome and spanned 4–4.5 kbp, consistent with regional epigenetically inherited centromeres. However, unlike other regional centromeres, there was no evidence of pericentromeric heterochromatin inC. lusitaniae. In particular, flanking genes were expressed at a similar level to the rest of the genome, and aURA3reporter inserted adjacent to a centromere was not repressed. In addition, regions flanking the centromeric core were not associated with hypoacetylated histones or a sirtuin deacetylase that generates heterochromatin in other yeast. Interestingly, the centromeric chromatin had a distinct pattern of histone modifications, being enriched for methylated H3K79 and H3R2 but lacking methylation of H3K4, which is found at other regional centromeres. Thus, not all regional centromeres require flanking heterochromatin.

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