Eunkyeong Kim1,2,†, Jun Kim1,3,*,†, Chuna Kim4 and Junho Lee1,2,3,*
1Department of Biological Sciences, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Korea,
2Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea, 3Research Institute of Basic Sciences, Seoul National University, Seoul 08826, Korea and 4Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro 125, Daejeon 34141, Korea
*To whom correspondence should be addressed.
†The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
Karyotype change and subsequent evolution is triggered by chromosome fusion and rearrangement events, which often occur when telomeres become dysfunctional. Telomeres protect linear chromosome ends from DNA damage responses (DDRs), and telomere dysfunction may result in genome instability. However, the complex chromosome end structures and the other possible consequences of telomere dysfunction have rarely been resolved at the nucleotide level due to the lack of the high-throughput methods needed to analyse these highly repetitive regions. Here we applied long-read sequencing technology to Caenorhabditis elegans survivor lines that emerged after telomere dysfunction. The survivors have preserved traces of DDRs in their genomes and our data revealed that variants generated by telomere dysfunction are accumulated along all chromosomes. The reconstruction of the chromosome end structures through de novo genome assemblies revealed diverse types of telomere damage processing at the nucleotide level. When telomeric repeats were totally eroded by telomere dysfunction, DDRs were mostly terminated by chromosome fusion events. We also partially reconstructed the most complex end structure and its DDR signatures, which would have been accumulated via multiple cell divisions. These finely resolved chromosome end structures suggest possible mechanisms regarding the repair processes after telomere dysfunction, providing insights into chromosome evolution in nature.