Loss of centromere function drives karyotype evolution in closely related Malassezia species
- Jawaharlal Nehru Centre for Advanced Scientific Research, India
- Duke University Medical Center, United States
- The Institute of Mathematical Sciences (HBNI), India
- Uppsala University, Sweden
- Agency for Science, Technology and Research, Singapore
Abstract
Genomic rearrangements associated with speciation often result in chromosome number variation among closely related species. Malassezia species show variable karyotypes ranging between 6 and 9 chromosomes. Here, we experimentally identified all 8 centromeres in M. sympodialis as 3 to 5 kb long kinetochore-bound regions spanning an AT-rich core and depleted of the canonical histone H3. Centromeres of similar sequence features were identified as CENP-A-rich regions in Malassezia furfur with 7 chromosomes, and histone H3 depleted regions in Malassezia slooffiae and Malassezia globosa with 9 chromosomes each. Analysis of synteny conservation across centromeres with newly generated chromosome-level genome assemblies suggests two distinct mechanisms of chromosome number reduction from an inferred 9-chromosome ancestral state: (a) chromosome breakage followed by loss of centromere DNA and (b) centromere inactivation accompanied by changes in DNA sequence following chromosome-chromosome fusion. We propose AT-rich centromeres drive karyotype diversity in the Malassezia species complex through breakage and inactivation.
Data availability
The Mtw1 ChIP sequencing reads reported in this paper have been deposited under NCBI BioProject (Accession number PRJNA509412). The genome sequence assemblies of M. globosa, M. slooffiae, and M. furfur have been deposited in GenBank with accession numbers SAMN10720087, SAMN10720088, and SAMN13341476 respectively.
-
Genome assembly of Malassezia slooffiaeGenBank, SAMN10720088.
-
Genome assembly of Malassezia globosaGenBank, SAMN10720087.
-
Genome assembly of Malassezia furfurGenBank, SAMN13341476.
-
Malassezia restricta CBS 7877 genome, complete sequenceNCBI BioSample, SAMN09377640.
-
Genome sequencing of Malassezia nana JCM 12085NCBI BioProject, PRJDB3735.
-
Genome sequencing of Malassezia dermatis JCM 11348NCBI BioProject, PRJDB3732.
-
Genome sequencing of Malassezia japonica JCM 11963NCBI BioProject, PRJDB3733.
Article and author information
Author details
Funding
Tata Innovation Fellowship (BT/HRT/35/01/03/2017)
- Kaustuv Sanyal
Department of Biotechnology , Ministry of Science and Technology (BT/INF/22/SP27679/2018)
- Kaustuv Sanyal
National Institutes of Health (R37 award-AI39115-21; R01 award-AI50113-15)
- Joseph Heitman
Agency for Science, Technology and Research (H18/01a0/016)
- Thomas L Dawson
Jawaharlal Nehru Centre for Advanced Scientific Research (Graduate student fellowship)
- Sundar Ram Sankaranarayanan
Science and Engineering Research Board (PDF/2016/002858)
- Md Hashim Reza
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Sankaranarayanan 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
-
- 3,433
- views
-
- 473
- downloads
-
- 48
- 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)
Loss of centromere function drives karyotype evolution in closely related Malassezia species
eLife 9:e53944.
https://doi.org/10.7554/eLife.53944
Further reading
-
- Biochemistry and Chemical Biology
- Genetics and Genomics
Deep Mutational Scanning (DMS) is an emerging method to systematically test the functional consequences of thousands of sequence changes to a protein target in a single experiment. Because of its utility in interpreting both human variant effects and protein structure-function relationships, it holds substantial promise to improve drug discovery and clinical development. However, applications in this domain require improved experimental and analytical methods. To address this need, we report novel DMS methods to precisely and quantitatively interrogate disease-relevant mechanisms, protein-ligand interactions, and assess predicted response to drug treatment. Using these methods, we performed a DMS of the melanocortin-4 receptor (MC4R), a G-protein-coupled receptor (GPCR) implicated in obesity and an active target of drug development efforts. We assessed the effects of >6600 single amino acid substitutions on MC4R’s function across 18 distinct experimental conditions, resulting in >20 million unique measurements. From this, we identified variants that have unique effects on MC4R-mediated Gαs- and Gαq-signaling pathways, which could be used to design drugs that selectively bias MC4R’s activity. We also identified pathogenic variants that are likely amenable to a corrector therapy. Finally, we functionally characterized structural relationships that distinguish the binding of peptide versus small molecule ligands, which could guide compound optimization. Collectively, these results demonstrate that DMS is a powerful method to empower drug discovery and development.
-
- Biochemistry and Chemical Biology
- Genetics and Genomics
5-Methylcytosine (m5C) is one of the posttranscriptional modifications in mRNA and is involved in the pathogenesis of various diseases. However, the capacity of existing assays for accurately and comprehensively transcriptome-wide m5C mapping still needs improvement. Here, we develop a detection method named DRAM (deaminase and reader protein assisted RNA methylation analysis), in which deaminases (APOBEC1 and TadA-8e) are fused with m5C reader proteins (ALYREF and YBX1) to identify the m5C sites through deamination events neighboring the methylation sites. This antibody-free and bisulfite-free approach provides transcriptome-wide editing regions which are highly overlapped with the publicly available bisulfite-sequencing (BS-seq) datasets and allows for a more stable and comprehensive identification of the m5C loci. In addition, DRAM system even supports ultralow input RNA (10 ng). We anticipate that the DRAM system could pave the way for uncovering further biological functions of m5C modifications.
