Telomerase-independent survival leads to a mosaic of complex subtelomere rearrangements inChlamydomonas reinhardtii

Abstract

Telomeres and subtelomeres, the genomic regions located at chromosome extremities, are essential for genome stability in eukaryotes. In the absence of the canonical maintenance mechanism provided by telomerase, telomere shortening induces genome instability. The landscape of the ensuing genome rearrangements is not accessible by short-read sequencing. Here, we leverage Oxford Nanopore Technologies long-read sequencing to survey the extensive repertoire of genome rearrangements in telomerase mutants of the model green microalga Chlamydomonas reinhardtii. In telomerase mutant strains grown for ~700 generations, most chromosome extremities were capped by short telomere sequences that were either recruited de novo from other loci or maintained in a telomerase-independent manner. Other extremities did not end with telomeres but only with repeated subtelomeric sequences. The subtelomeric elements, including rDNA, were massively rearranged and involved in breakage-fusion-bridge cycles, translocations, recombinations and chromosome circularization. These events were established progressively over time and displayed heterogeneity at the subpopulation level. New telomere-capped extremities composed of sequences originating from more internal genomic regions were associated with high DNA methylation, suggesting that de novo heterochromatin formation contributes to restore chromosome end stability in C. reinhardtii. The diversity of alternative strategies to maintain chromosome integrity and the variety of rearrangements found in telomerase mutants are remarkable and illustrate genome plasticity at short timescales.

Atlas of telomeric repeat diversity inArabidopsis thaliana

“…Since the telomeres of telomerase-deficient mutants progressively shorten only for a few generations, after which no further shortening is observed (Chaux et al 2023), we hypothesize that a fraction of canonical repeats is not involved directly in telomere maintenance. The next two questions concern the two chromosome ends next to the 45S rDNA clusters.…”