scholarly journals Evolutionary cell biology of chromosome segregation: insights from trypanosomes

Open Biology ◽  
2013 ◽  
Vol 3 (5) ◽  
pp. 130023 ◽  
Author(s):  
Bungo Akiyoshi ◽  
Keith Gull
Keyword(s):  
Chromosome Segregation ◽  
Cell Biology ◽  
Design Principle ◽  
Genetic Material ◽  
Evolutionary Time ◽  
Origin And Evolution ◽  
Eukaryotic Chromosome ◽  
Evolutionary Origins ◽  
Spindle Microtubules ◽  
Kinetoplastid Parasite

Faithful transmission of genetic material is essential for the survival of all organisms. Eukaryotic chromosome segregation is driven by the kinetochore that assembles onto centromeric DNA to capture spindle microtubules and govern the movement of chromosomes. Its molecular mechanism has been actively studied in conventional model eukaryotes, such as yeasts, worms, flies and human. However, these organisms are closely related in the evolutionary time scale and it therefore remains unclear whether all eukaryotes use a similar mechanism. The evolutionary origins of the segregation apparatus also remain enigmatic. To gain insights into these questions, it is critical to perform comparative studies. Here, we review our current understanding of the mitotic mechanism in Trypanosoma brucei , an experimentally tractable kinetoplastid parasite that branched early in eukaryotic history. No canonical kinetochore component has been identified, and the design principle of kinetochores might be fundamentally different in kinetoplastids. Furthermore, these organisms do not appear to possess a functional spindle checkpoint that monitors kinetochore–microtubule attachments. With these unique features and the long evolutionary distance from other eukaryotes, understanding the mechanism of chromosome segregation in T. brucei should reveal fundamental requirements for the eukaryotic segregation machinery, and may also provide hints about the origin and evolution of the segregation apparatus.

scholarly journals Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly

2021 ◽  
Author(s):  
Stephen M Hinshaw ◽  
Yun Quan ◽  
Jiaxi Cai ◽  
Ann Zhou ◽  
Huilin Zhou
Keyword(s):  
Chromosome Segregation ◽  
Regulatory Mechanism ◽  
Phosphorylation Sites ◽  
Biochemical System ◽  
Eukaryotic Chromosome ◽  
Kinetochore Assembly ◽  
Spindle Microtubules ◽  
Pest Region ◽  
Microtubule Poisons ◽  
In Cells

Kinetochores control eukaryotic chromosome segregation by connecting chromosomal centromeres to spindle microtubules. Duplication of centromeric DNA necessitates kinetochore disassembly and subsequent reassembly on the nascent sisters. To search for a regulatory mechanism that controls the earliest steps of kinetochore assembly, we studied Mif2/CENP-C, an essential basal component. We found that Polo-like kinase (Cdc5) and Dbf4-dependent kinase (DDK) phosphorylate the conserved PEST region of Mif2/CENP-C and that this phosphorylation directs inner kinetochore assembly. Mif2 phosphorylation promotes kinetochore assembly in a reconstituted biochemical system, and it strengthens Mif2 localization at centromeres in cells. Disrupting one or more phosphorylation sites in the Mif2-PEST region progressively impairs cellular fitness and sensitizes cells to microtubule poisons. The most severe Mif2-PEST mutations are lethal in cells lacking otherwise non-essential Ctf19 complex factors. These data suggest that multi-site phosphorylation of Mif2/CENP-C is a robust switch that controls inner kinetochore assembly, ensuring accurate chromosome segregation.

scholarly journals The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle

Open Biology ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 200051 ◽  
Author(s):  
Kathryn Kixmoeller ◽  
Praveen Kumar Allu ◽  
Ben E. Black
Keyword(s):  
Chromosome Segregation ◽  
Molecular Complexes ◽  
Molecular Models ◽  
Chromosomal Locus ◽  
Centromeric Chromatin ◽  
Eukaryotic Chromosome ◽  
The Core ◽  
Histone H3 Variant ◽  
Spindle Microtubules ◽  
Insight Into

Eukaryotic chromosome segregation relies upon specific connections from DNA to the microtubule-based spindle that forms at cell division. The chromosomal locus that directs this process is the centromere, where a structure called the kinetochore forms upon entry into mitosis. Recent crystallography and single-particle electron microscopy have provided unprecedented high-resolution views of the molecular complexes involved in this process. The centromere is epigenetically specified by nucleosomes harbouring a histone H3 variant, CENP-A, and we review recent progress on how it differentiates centromeric chromatin from the rest of the chromosome, the biochemical pathway that mediates its assembly and how two non-histone components of the centromere specifically recognize CENP-A nucleosomes. The core centromeric nucleosome complex (CCNC) is required to recruit a 16-subunit complex termed the constitutive centromere associated network (CCAN), and we highlight recent structures reported of the budding yeast CCAN. Finally, the structures of multiple modular sub-complexes of the kinetochore have been solved at near-atomic resolution, providing insight into how connections are made to the CCAN on one end and to the spindle microtubules on the other. One can now build molecular models from the DNA through to the physical connections to microtubules.

scholarly journals The unconventional kinetoplastid kinetochore: from discovery toward functional understanding

2016 ◽  
Vol 44 (5) ◽  
pp. 1201-1217 ◽  
Author(s):  
Bungo Akiyoshi
Keyword(s):  
Dna Binding ◽  
Chromosome Segregation ◽  
Protein Complex ◽  
Fundamental Function ◽  
Centromeric Dna ◽  
Eukaryotic Chromosome ◽  
Ndc80 Complex ◽  
Functional Understanding ◽  
Macromolecular Protein ◽  
Spindle Microtubules

The kinetochore is the macromolecular protein complex that drives chromosome segregation in eukaryotes. Its most fundamental function is to connect centromeric DNA to dynamic spindle microtubules. Studies in popular model eukaryotes have shown that centromere protein (CENP)-A is critical for DNA-binding, whereas the Ndc80 complex is essential for microtubule-binding. Given their conservation in diverse eukaryotes, it was widely believed that all eukaryotes would utilize these components to make up a core of the kinetochore. However, a recent study identified an unconventional type of kinetochore in evolutionarily distant kinetoplastid species, showing that chromosome segregation can be achieved using a distinct set of proteins. Here, I review the discovery of the two kinetochore systems and discuss how their studies contribute to a better understanding of the eukaryotic chromosome segregation machinery.

scholarly journals Divergent polo box domains underpin the unique kinetoplastid kinetochore

Open Biology ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 150206 ◽  
Author(s):  
Olga O. Nerusheva ◽  
Bungo Akiyoshi
Keyword(s):  
Trypanosoma Brucei ◽  
Chromosome Segregation ◽  
Sequence Similarity ◽  
Rich Region ◽  
Significant Similarity ◽  
Centromeric Dna ◽  
Eukaryotic Chromosome ◽  
Duplication Events ◽  
Spindle Microtubules

Kinetochores are macromolecular machines that drive eukaryotic chromosome segregation by interacting with centromeric DNA and spindle microtubules. While most eukaryotes possess conventional kinetochore proteins, evolutionarily distant kinetoplastid species have unconventional kinetochore proteins, composed of at least 19 proteins (KKT1–19). Polo-like kinase (PLK) is not a structural kinetochore component in either system. Here, we report the identification of an additional kinetochore protein, KKT20, in Trypanosoma brucei . KKT20 has sequence similarity with KKT2 and KKT3 in the Cys-rich region, and all three proteins have weak but significant similarity to the polo box domain (PBD) of PLK. These divergent PBDs of KKT2 and KKT20 are sufficient for kinetochore localization in vivo . We propose that the ancestral PLK acquired a Cys-rich region and then underwent gene duplication events to give rise to three structural kinetochore proteins in kinetoplastids.

scholarly journals Comets (Existing Populations)

1994 ◽  
Vol 160 ◽  
pp. 77-94
Author(s):  
Ľ. Kresák
Keyword(s):  
Kuiper Belt ◽  
Dynamical Evolution ◽  
Oort Cloud ◽  
Survival Times ◽  
Evolutionary Time ◽  
Origin And Evolution ◽  
History Of ◽  
The Individual ◽  
Evolutionary Paths

The definition, population, extent, origin and evolution of the individual subsystems of comets and transitions between them are discussed, together with presentation of the relevant statistical data and their changes with time. The largest outer subsystems are unobservable, but their existence is documented by the necessity of progressive replenishment of the observable populations, with limited survival times. There is persuasive evidence for two different evolutionary paths, one from the Oort cloud and another from the Kuiper belt. While the extent and accuracy of the data available is increasing rapidly, the Jupiter family of comets is the only one for which the evolutionary time scales do not exceed by many orders of magnitude the history of astronomical observations. The individual comet populations differ from one another not only by the distribution of orbits, but also by the size distribution and aging rate of their members. Their dynamical evolution is coupled with disintegration processes, which make it questionable whether the present state can be interpreted as a long-term average.

scholarly journals Reticulate evolution in eukaryotes: origin and evolution of the nitrate assimilation pathway

2018 ◽  
Author(s):  
Eduard Ocaña-Pallarès ◽  
Sebastián R. Najle ◽  
Claudio Scazzocchio ◽  
Iñaki Ruiz-Trillo
Keyword(s):  
Nitrate Reductase ◽  
Gene Fusion ◽  
Evolutionary History ◽  
Transcriptional Control ◽  
Genetic Material ◽  
Nitrate Assimilation ◽  
Nitrogen Sources ◽  
Reticulate Evolution ◽  
Origin And Evolution ◽  
Ideal Object

AbstractGenes and genomes can evolve through interchanging genetic material, this leading to reticular evolutionary patterns. However, the importance of reticulate evolution in eukaryotes, and in particular of horizontal gene transfer (HGT), remains controversial. Given that metabolic pathways with taxonomically-patchy distributions can be indicative of HGT events, the eukaryotic nitrate assimilation pathway is an ideal object of investigation, as previous results revealed a patchy distribution and suggested one crucial HGT event. We studied the evolution of this pathway through both multi-scale bioinformatic and experimental approaches. Our taxon-rich genomic screening shows this pathway to be present in more lineages than previously proposed and that nitrate assimilation is restricted to autotrophs and to distinct osmotrophic groups. Our phylogenies show a pervasive role of HGT, with three bacterial transfers contributing to the pathway origin, and at least seven well-supported transfers between eukaryotes. Our results, based on a larger dataset, differ from the previously proposed transfer of a nitrate assimilation cluster from Oomycota (Stramenopiles) to Dikarya (Fungi, Opisthokonta). We propose a complex HGT path involving at least two cluster transfers between Stramenopiles and Opisthokonta. We also found that gene fusion played an essential role in this evolutionary history, underlying the origin of the canonical eukaryotic nitrate reductase, and of a novel nitrate reductase in Ichthyosporea (Opisthokonta). We show that the ichthyosporean pathway, including this novel nitrate reductase, is physiologically active and transcriptionally co-regulated, responding to different nitrogen sources; similarly to distant eukaryotes with independent HGT-acquisitions of the pathway. This indicates that this pattern of transcriptional control evolved convergently in eukaryotes, favoring the proper integration of the pathway in the metabolic landscape. Our results highlight the importance of reticulate evolution in eukaryotes, by showing the crucial contribution of HGT and gene fusion in the evolutionary history of the nitrate assimilation pathway.

scholarly journals Coelacanth SERINC2 inhibits HIV-1 infectivity and is counteracted by envelope glycoprotein from foamy virus

2021 ◽  
Author(s):  
Pavitra Ramdas ◽  
Vipin Bhardwaj ◽  
Aman Singh ◽  
Nagarjun Vijay ◽  
Ajit Chande
Keyword(s):  
Foamy Virus ◽  
Virus Envelope ◽  
Origin And Evolution ◽  
Evolutionary Origins ◽  
Evolutionarily Conserved ◽  
Foamy Viruses ◽  
Future Drug ◽  
Steady State Levels ◽  
Infection Inhibition ◽  
Hiv 1

SERINC5 restricts nef-defective HIV-1 by affecting early steps of the virus life cycle. Distant retroviruses with a wide host-range encode virulent factors in response to the challenge by SERINC5. Yet, the evolutionary origins of this anti-retroviral activity, its prevalence among the paralogs, and its ability to target retroviruses remain understudied. In agreement with previous studies, we find that four human SERINC paralogs inhibit nef-defective HIV-1, with SERINC2 being an exception. Here, we demonstrate that this lack of activity in human SERINC2 is associated with its post-whole genome duplication (WGD) divergence, as evidenced by the ability of pre-WGD orthologs from yeast, fly, and a post-WGD-proximate SERINC2 from coelacanth to inhibit the virus. Intriguingly, Nef is unable to counter coelacanth SERINC2, indicating that such activity was directed towards other retroviruses found in coelacanth (like foamy viruses). However, foamy-derived vectors are intrinsically resistant to the action of SERINC2, and we show that the foamy virus envelope confers this resistance by affecting its steady-state levels. Our study highlights an ancient origin of anti-retroviral activity in SERINCs and a hitherto unknown interaction with a foamy virus. Importance SERINC5 constitutes a critical barrier to the propagation of retroviruses as highlighted by parallel emergence of anti-SERINC5 activities among distant retroviral lineages. Therefore, understanding the origin and evolution of these host factors will provide key information about virus-host relationships that can be exploited for future drug development. Here we show that SERINC5-mediated nef-defective HIV-1 infection inhibition is evolutionarily conserved. SERINC2 from coelacanth restricts HIV-1 and it was functionally adapted to target foamy viruses. Our findings provide insights into the evolutionary origin of anti-retroviral activity in SERINC gene family and uncover the role of SERINCs in shaping the long-term conflicts between retroviruses and their hosts.

scholarly journals Differential requirement for Bub1 and Bub3 in regulation of meiotic versus mitotic chromosome segregation

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Gisela Cairo ◽  
Anne M. MacKenzie ◽  
Soni Lacefield
Keyword(s):  
Chromosome Segregation ◽  
Protein Phosphatase ◽  
Mitotic Chromosome ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Chromosome Missegregation ◽  
Anaphase Onset ◽  
Spindle Microtubules

Accurate chromosome segregation depends on the proper attachment of kinetochores to spindle microtubules before anaphase onset. The Ipl1/Aurora B kinase corrects improper attachments by phosphorylating kinetochore components and so releasing aberrant kinetochore–microtubule interactions. The localization of Ipl1 to kinetochores in budding yeast depends upon multiple pathways, including the Bub1–Bub3 pathway. We show here that in meiosis, Bub3 is crucial for correction of attachment errors. Depletion of Bub3 results in reduced levels of kinetochore-localized Ipl1 and concomitant massive chromosome missegregation caused by incorrect chromosome–spindle attachments. Depletion of Bub3 also results in shorter metaphase I and metaphase II due to premature localization of protein phosphatase 1 (PP1) to kinetochores, which antagonizes Ipl1-mediated phosphorylation. We propose a new role for the Bub1–Bub3 pathway in maintaining the balance between kinetochore localization of Ipl1 and PP1, a balance that is essential for accurate meiotic chromosome segregation and timely anaphase onset.

scholarly journals Basic mechanism of eukaryotic chromosome segregation

2005 ◽  
Vol 360 (1455) ◽  
pp. 609-621 ◽  
Author(s):  
Mitsuhiro Yanagida
Keyword(s):  
Chromosome Segregation ◽  
Protein Modification ◽  
Topoisomerase Ii ◽  
Cell Cycle Control ◽  
Basic Feature ◽  
Basic Mechanism ◽  
Specific Protein ◽  
Eukaryotic Chromosome ◽  
Mitotic Cyclin ◽  
A Cell

We now have firm evidence that the basic mechanism of chromosome segregation is similar among diverse eukaryotes as the same genes are employed. Even in prokaryotes, the very basic feature of chromosome segregation has similarities to that of eukaryotes. Many aspects of chromosome segregation are closely related to a cell cycle control that includes stage-specific protein modification and proteolysis. Destruction of mitotic cyclin and securin leads to mitotic exit and separase activation, respectively. Key players in chromosome segregation are SMC-containing cohesin and condensin, DNA topoisomerase II, APC/C ubiquitin ligase, securin–separase complex, aurora passengers, and kinetochore microtubule destabilizers or regulators. In addition, the formation of mitotic kinetochore and spindle apparatus is absolutely essential. The roles of principal players in basic chromosome segregation are discussed: most players have interphase as well as mitotic functions. A view on how the centromere/kinetochore is formed is described.

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