Abstract
AbstractGenomic 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献