Centromere-mediated chromosome break drives karyotype evolution in closely relatedMalasseziaspecies

AbstractIntra-chromosomal or inter-chromosomal genomic rearrangements often lead to speciation (1). Loss or gain of a centromere leads to alterations in chromosome number in closely related species. Thus, centromeres can enable tracing the path of evolution from the ancestral to a derived state (2). TheMalasseziaspecies complex of the phylum Basiodiomycota shows remarkable diversity in chromosome number ranging between six and nine chromosomes (3–5). To understand these transitions, we experimentally identified all eight centromeres as binding sites of an evolutionarily conserved outer kinetochore protein Mis12/Mtw1 inM. sympodialis. The 3 to 5 kb centromere regions share an AT-rich, poorly transcribed core region enriched with a 12 bp consensus motif. We also mapped nine such AT-rich centromeres inM. globosaand the related speciesMalassezia restrictaandMalassezia slooffiae. While eight predicted centromeres were found within conserved synteny blocks between these species andM. sympodialis, the remaining centromere inM. globosa(MgCEN2) or its orthologous centromere inM. slooffiae(MslCEN4) andM. restricta(MreCEN8) mapped to a synteny breakpoint compared withM. sympodialis. Taken together, we provide evidence that breakage and loss of a centromere (CEN2) in an ancestralMalasseziaspecies possessing nine chromosomes resulted in fewer chromosomes inM. sympodialis. Strikingly, the predicted centromeres of all closely relatedMalasseziaspecies map to an AT-rich core on each chromosome that also shows enrichment of the 12 bp sequence motif. We propose that centromeres are fragile AT-rich sites driving karyotype diversity through breakage and inactivation in these and other species.Significance statementThe number of chromosomes can vary between closely related species. Centromere loss destabilizes chromosomes and results in reduced number of chromosomes to drive speciation. A series of evidence from studies on various cancers suggest that an imbalance in kinetochore-microtubule attachments results in breaks at the centromeres. To understand if such events can cause chromosome number changes in nature, we studied six species ofMalassezia, of which three possess eight chromosomes and others have nine chromosomes each. We find signatures of chromosome breakage at the centromeres in organisms having nine chromosomes. We propose that the break at the centromere followed by fusions of acentric chromosomes to other chromosomes could be a plausible mechanism shaping the karyotype ofMalasseziaand related organisms.ClassificationBiological sciences, Genetics