Supplementary table S1. Coordinates of centromeres and their GC content in M. sympodialis.Coordinates and length of Mtw1-enriched regions in comparison with that of the core centromeres in M. sympodialis. Chromosome numberCore centromere

The thermotolerant multidrug-resistant ascomycete Candida auris rapidly emerged since 2009 causing systemic infections worldwide and simultaneously evolved in different geographical zones. The molecular events that orchestrated this sudden emergence of the killer fungus remain mostly elusive. Here, we identify centromeres in C. auris and related species, using a combined approach of chromatin immunoprecipitation and comparative genomic analyses. We find that C. auris and multiple other species in the Clavispora/Candida clade shared a conserved small regional GC-poor centromere landscape lacking pericentromeres or repeats. Further, a centromere inactivation event led to karyotypic alterations in this species complex. Interspecies genome analysis identified several structural chromosomal changes around centromeres. In addition, centromeres are found to be rapidly evolving loci among the different geographical clades of the same species of C. auris. Finally, we reveal an evolutionary trajectory of the unique karyotype associated with clade 2 that consists of the drug-susceptible isolates of C. auris. IMPORTANCE Candida auris, the killer fungus, emerged as different geographical clades, exhibiting multidrug resistance and high karyotype plasticity. Chromosomal rearrangements are known to play key roles in the emergence of new species, virulence, and drug resistance in pathogenic fungi. Centromeres, the genomic loci where microtubules attach to separate the sister chromatids during cell division, are known to be hot spots of breaks and downstream rearrangements. We identified the centromeres in C. auris and related species to study their involvement in the evolution and karyotype diversity reported in C. auris. We report conserved centromere features in 10 related species and trace the events that occurred at the centromeres during evolution. We reveal a centromere inactivation-mediated chromosome number change in these closely related species. We also observe that one of the geographical clades, the East Asian clade, evolved along a unique trajectory, compared to the other clades and related species.

34Genomic rearrangements associated with speciation often result in chromosome number 35 variation among closely related species. Malassezia species show variable karyotypes ranging 36 between 6 and 9 chromosomes. Here, we experimentally identified all 8 centromeres in M. 37 sympodialis as 3 to 5 kb long kinetochore-bound regions spanning an AT-rich core and depleted 38 of the canonical histone H3. Centromeres of similar sequence features were identified as CENP-39 A-rich regions in Malassezia furfur with 7 chromosomes, and histone H3 depleted regions in 40 Malassezia slooffiae and Malassezia globosa with 9 chromosomes each. Analysis of synteny 41 conservation across centromeres with newly generated chromosome-level genome assemblies 42 suggests two distinct mechanisms of chromosome number reduction from an inferred 9-43 chromosome ancestral state: (a) chromosome breakage followed by loss of centromere DNA 44 and (b) centromere inactivation accompanied by changes in DNA sequence following 45 chromosome-chromosome fusion. We propose AT-rich centromeres drive karyotype diversity in 46 the Malassezia species complex through breakage and inactivation. 47 107 5 that exhibit chromosome number variation. Malassezia species are lipid-dependent 108 basidiomycetous fungi that are naturally found as part of the animal skin microbiome (Theelen et 109 al. , 2018). The Malassezia genus presently includes 18 species divided into three clades -A, B, 110 and C. These species also have unusually compact genomes of less than 9 Mb, organized into 6 111 to 9 chromosomes as revealed by electrophoretic karyotyping of some of these species 112 (Boekhout and Bosboom, 1994, Boekhout et al., 1998, Wu et al., 2015. Fungemia-associated 113 species like Malassezia furfur belong to Clade A. Clade B includes common inhabitants of 114 human skin that are phylogenetically clustered into two subgroups namely Clade B1 that 115 contains Malassezia globosa and Malassezia restricta and Clade B2 that contains Malassezia 116 sympodialis and related species. Clade C includes Malassezia slooffiae and Malassezia cuniculi 117 which diverged earlier from a Malassezia common ancestor (Wu et al., 2015, Lorch et al., 2018). 118 Besides humans, Malassezia species have been detected on the skin of animals. For 119 example, M. slooffiae was isolated from cows and goats, M. equina from horses, M. brasiliensis 120 and M. psittaci from parrots, and a cold-tolerant species M. vesperilionis isolated from bats 121 (Lorch et al., 2018. Additionally, culture-independent studies of fungi from 122 environmental samples showed that the Malassezia species closely realted to those found on 123 human skin were also detected in diverse niches such as deep-sea vents, soil invertebrates, 124 hydrothermal vents, corals, and Antarctic soils (Amend, 2014). More than ten Malassezia species 125 have been detected as a part of the human skin microbiome (Findley and Grice, 2014). The 126 human skin commensals such as M. globosa, M. restricta, and M. sympodialis have been 127 associ...

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Genomic surveillance in response to coronavirus disease (COVID-19) pandemic is crucial for tracking spread, identify variants of concern (VoCs) and understand the evolution of its etiological agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). India has experienced three waves of COVID-19 cases, which includes a deadly wave of COVID-19 that was driven by the Delta lineages (second/Delta wave) followed by another wave driven by the Omicron lineages (third/Omicron wave). These waves were particularly dramatic in the metropolitan cities due to high population density. We evaluated the prevalence, and mutational spectrum of SARS-CoV-2 variants/lineages in one such megapolis, Bengaluru city, across these three waves between October 2020 and June 2022. 15,134 SARS-CoV-2 samples were subjected to whole genome sequencing (WGS). Phylogenetic analysis revealed, SARS-CoV-2 variants in Bengaluru city belonged to 18 clades and 196 distinct lineages. As expected, the Delta lineages were the most dominant lineages during the second wave of COVID-19. The Omicron lineage BA.2 and its sublineages accounted for most of the COVID-19 cases in the third wave. Most number of amino acid changes were observed in spike protein. Among the 18 clades, majority of the mutations and least similarity at nucleotide sequence level with the reference genome were observed in Omicron clades.