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
-
- 3,389
- views
-
- 462
- 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
-
- Genetics and Genomics
Heritable fragile bone disorders (FBDs), ranging from multifactorial to rare monogenic conditions, are characterized by an elevated fracture risk. Validating causative genes and understanding their mechanisms remain challenging. We assessed a semi-high throughput zebrafish screening platform for rapid in vivo functional testing of candidate FBD genes. Six genes linked to severe recessive osteogenesis imperfecta (OI) and four associated with bone mineral density (BMD) from genome-wide association studies were analyzed using CRISPR/Cas9-based crispant screening in F0 mosaic founder zebrafish. Next-generation sequencing confirmed high indel efficiency (mean 88%), mimicking stable knock-out models. Skeletal phenotyping at 7, 14, and 90 days post-fertilization (dpf) using microscopy, Alizarin Red S staining, and microCT was performed. Larval crispants showed variable osteoblast and mineralization phenotypes, while adult crispants displayed consistent skeletal defects, including malformed neural and haemal arches, vertebral fractures and fusions, and altered bone volume and density. In addition, aldh7a1 and mbtps2 crispants experienced increased mortality due to severe skeletal deformities. RT-qPCR revealed differential expression of osteogenic markers bglap and col1a1a, highlighting their biomarker potential. Our results establish zebrafish crispant screening as a robust tool for FBD gene validation, combining skeletal and molecular analyses across developmental stages to uncover novel insights into gene functions in bone biology.
-
- Genetics and Genomics
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts. Integrating childhood obesity GWAS summary statistics with our existing 3D genomic datasets for 57 human cell types, consisting of high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq, and RNA-seq, we applied stratified LD score regression and calculated the proportion of genome-wide SNP heritability attributable to cell type-specific features, revealing pancreatic alpha cell enrichment as the most statistically significant. Subsequent chromatin contact-based fine-mapping was carried out for genome-wide significant childhood obesity loci and their linkage disequilibrium proxies to implicate effector genes, yielded the most abundant number of candidate variants and target genes at the BDNF, ADCY3, TMEM18, and FTO loci in skeletal muscle myotubes and the pancreatic beta-cell line, EndoC-BH1. One novel implicated effector gene, ALKAL2 – an inflammation-responsive gene in nerve nociceptors – was observed at the key TMEM18 locus across multiple immune cell types. Interestingly, this observation was also supported through colocalization analysis using expression quantitative trait loci (eQTL) derived from the Genotype-Tissue Expression (GTEx) dataset, supporting an inflammatory and neurologic component to the pathogenesis of childhood obesity. Our comprehensive appraisal of 3D genomic datasets generated in a myriad of different cell types provides genomic insights into pediatric obesity pathogenesis.
