Abstract
Genomic instability caused by chromosomal rearrangements has severe consequences for organismal fitness and progression of cancerous cell lines. The triggers of destabilized chromosomes remain poorly understood but are often assumed to be associated with fragile sites. Here, we retrace a runaway chromosomal degeneration process observed in a fungal pathogen using telomere-to-telomere assemblies across an experimental pedigree. We show that the same fragile sites triggered reproducible, large-scale rearrangements through non-allelic recombination. Across the four-generation pedigree, chromosomal rearrangements were accompanied by non-disjunction events and caused aneuploid progeny to carry up to four chromosomal copies. We identify a specific transposable element as the most likely trigger for the repeated chromosomal degeneration. The element is associated with higher virulence of the pathogen and has undergone a burst increasing copy numbers across the genome. Chromosome sequences are also targeted by a genome defense mechanism active on duplicated sequences, which may contribute to decay. Our work identifies the exact sequence triggers initiating chromosome instability and perpetuating degenerative cycles. Dissecting proximate causes leading to run-away chromosomal degeneration expands our understanding of chromosomal evolution beyond cancer lines.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Data availability: The genome assembly and annotation for 1A5, 1E4 and 3D7 genome are available at the European Nucleotide Archive (http://www.ebi.ac.uk/ena) under accession numbers PRJEB15648, PRJEB20900 and PRJEB14341. Progeny genomes are available under the project PRJNA645795.