Spatial inter-centromeric interactions facilitated the emergence of evolutionary new centromeres

  1. Krishnendu Guin
  2. Yao Chen
  3. Radha Mishra
  4. Siti Rawaidah B M Muzaki
  5. Bhagya C Thimmappa
  6. Caoimhe E O'Brien
  7. Geraldine Butler
  8. Amartya Sanyal  Is a corresponding author
  9. Kaustuv Sanyal  Is a corresponding author
  1. Jawaharlal Nehru Centre for Advanced Scientific Research, India
  2. Nanyang Technological University, Singapore
  3. University College Dublin, Ireland
  4. Conway Institute, University College Dublin, Ireland

Abstract

Centromeres of Candida albicans form on unique and different DNA sequences but a closely related species, Candida tropicalis, possesses homogenized inverted repeat (HIR)-associated centromeres. To investigate the mechanism of centromere type transition, we improved the fragmented genome assembly and constructed a chromosome-level genome assembly of C. tropicalis by employing PacBio sequencing, chromosome conformation capture sequencing (3C-seq), chromoblot, and genetic analysis of engineered aneuploid strains. Further, we analyzed the 3D genome organization using 3C-seq data, which revealed spatial proximity among the centromeres as well as telomeres of seven chromosomes in C. tropicalis. Intriguingly, we observed evidence of inter-centromeric translocations in the common ancestor of C. albicans and C. tropicalis. Identification of putative centromeres in closely related Candida sojae, Candida viswanathii and Candida parapsilosis indicates loss of ancestral HIR-associated centromeres and establishment of evolutionary new centromeres (ENCs) in C. albicans. We propose that spatial proximity of the homologous centromere DNA sequences facilitated karyotype rearrangements and centromere type transitions in human pathogenic yeasts of the CUG-Ser1 clade.

Data availability

All sequencing data reported in the study and the genome assembly of C. tropicalis and C. sojae have been submitted to NCBI under the BioProject accession numbers PRJNA596050 and PRJNA604451

The following data sets were generated

Article and author information

Author details

  1. Krishnendu Guin

    Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6957-465X
  2. Yao Chen

    Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  3. Radha Mishra

    Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Siti Rawaidah B M Muzaki

    Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  5. Bhagya C Thimmappa

    Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  6. Caoimhe E O'Brien

    University College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  7. Geraldine Butler

    Conway Institute, University College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  8. Amartya Sanyal

    Nanyang Technological University, Singapore, Singapore
    For correspondence
    asanyal@ntu.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2109-4478
  9. Kaustuv Sanyal

    Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
    For correspondence
    sanyal@jncasr.ac.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6611-4073

Funding

Council of Scientific and Industrial Research (Shyama Prasad Mukherjee Fellowship 07/733(0181)/2013-EMR-I)

  • Krishnendu Guin

Department of Biotechnology , Ministry of Science and Technology (BT/PR27490/Med/29/1323/2018)

  • Kaustuv Sanyal

Ministry of Education - Singapore (RG39/18)

  • Amartya Sanyal

Department of Biotechnology , Ministry of Science and Technology

  • Kaustuv Sanyal

Nanyang Technological University (Nanyang Assistant Professorship grant)

  • Amartya Sanyal

Department of Biotechnology , Ministry of Science and Technology

  • Kaustuv Sanyal

Department of Biotechnology , Ministry of Science and Technology

  • Kaustuv Sanyal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Job Dekker, University of Massachusetts Medical School, United States

Version history

  1. Received: May 4, 2020
  2. Accepted: May 22, 2020
  3. Accepted Manuscript published: May 29, 2020 (version 1)
  4. Version of Record published: June 12, 2020 (version 2)
  5. Version of Record updated: June 30, 2020 (version 3)

Copyright

© 2020, Guin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,919
    views
  • 337
    downloads
  • 24
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Krishnendu Guin
  2. Yao Chen
  3. Radha Mishra
  4. Siti Rawaidah B M Muzaki
  5. Bhagya C Thimmappa
  6. Caoimhe E O'Brien
  7. Geraldine Butler
  8. Amartya Sanyal
  9. Kaustuv Sanyal
(2020)
Spatial inter-centromeric interactions facilitated the emergence of evolutionary new centromeres
eLife 9:e58556.
https://doi.org/10.7554/eLife.58556

Share this article

https://doi.org/10.7554/eLife.58556

Further reading

    1. Chromosomes and Gene Expression
    Allison Coté, Aoife O'Farrell ... Arjun Raj
    Research Article

    Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Maria L Adelus, Jiacheng Ding ... Casey E Romanoski
    Research Article

    Heterogeneity in endothelial cell (EC) sub-phenotypes is becoming increasingly appreciated in atherosclerosis progression. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking. Multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs) exposed to activating environments characteristic of the atherosclerotic microenvironment in vitro. Meta-analysis of single-cell transcriptomes across 17 human ex vivo arterial specimens was performed and two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and ex vivo cell profiles. HAEC cultures were reproducibly populated by four major clusters with distinct pathway enrichment profiles and modest heterogeneous responses: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Quantitative comparisons between in vitro and ex vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated single-nucleotide polymorphisms from Genome Wide Association Studies (GWAS), suggesting that these cell phenotypes harbor CAD-modulating mechanisms. Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and ex vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.