Abstract

The human fungal pathogen Cryptococcus deuterogattii is RNAi-deficient and lacks active transposons in its genome. C. deuterogattii has regional centromeres that contain only transposon relics. To investigate the impact of centromere loss on the C. deuterogattii genome, either centromere 9 or 10 was deleted. Deletion of either centromere resulted in neocentromere formation and interestingly, the genes covered by these neocentromeres maintained wild-type expression levels. In contrast to cen9∆ mutants, cen10∆ mutant strains exhibited growth defects and were aneuploid for chromosome 10. At an elevated growth temperature (37°C), the cen10∆ chromosome was found to have undergone fusion with another native chromosome in some isolates and this fusion restored wild-type growth. Following chromosomal fusion, the neocentromere was inactivated, and the native centromere of the fused chromosome served as the active centromere. The neocentromere formation and chromosomal fusion events observed in this study in C. deuterogattii may be similar to events that triggered genomic changes within the Cryptococcus/Kwoniella species complex and may contribute to speciation throughout the eukaryotic domain.

Highlights

  • Eukaryotic organisms have linear chromosomes with specialized regions: telomeres that cap the ends, origins of replication, and centromeres that are critical for chromosome segregation

  • Fungal regional centromeres range from the small centromeres of Candida albicans, to the large regional centromeres described in Neurospora crassa, (Sanyal et al, 2004; Smith et al, 2011)

  • The most prominent examples are the centromeres of Schizosaccharomyces pombe, which have a CENP-A-enriched region comprised of a central core flanked by heterochromatic pericentric regions divided into outer and inner repeats (Ishii et al, 2008; Rhind et al, 2011)

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Summary

Introduction

Eukaryotic organisms have linear chromosomes with specialized regions: telomeres that cap the ends, origins of replication, and centromeres that are critical for chromosome segregation. Centromeres contain higher-order a-satellite DNA arrays that span 0.1 to 4.8 Mb (McNulty and Sullivan, 2018), which is in contrast to most fungal centromeres, which contain transposable elements and repetitive sequences (Friedman and Freitag, 2017). Fungal regional centromeres range from the small centromeres of Candida albicans, (the CENP-A enriched regions range from 2 to 3.3 kb and are located in 4 to 18 kb open-reading frame ORF-free regions), to the large regional centromeres described in Neurospora crassa, (which range from 174 to 287 kb and consist mainly of truncated transposable elements) (Sanyal et al, 2004; Smith et al, 2011). Budding yeast have sequence-dependent centromeres, which are short and have a conserved organization with three centromere DNA elements (consensus DNA elements (CDEs) I-III) (Kobayashi et al, 2015). The budding yeast Naumovozyma castellii has unique consensus DNA elements that differ from those of other budding yeast species (Kobayashi et al, 2015)

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