Catastrophic chromosomal restructuring during genome elimination in plants

Abstract

Genome instability is associated with mitotic errors and cancer. This phenomenon can lead to deleterious rearrangements, but also genetic novelty, and many questions regarding its genesis, fate and evolutionary role remain unanswered. Here, we describe extreme chromosomal restructuring during genome elimination, a process resulting from hybridization of Arabidopsis plants expressing different centromere histones H3. Shattered chromosomes are formed from the genome of the haploid inducer, consistent with genomic catastrophes affecting a single, laggard chromosome compartmentalized within a micronucleus. Analysis of breakpoint junctions implicates breaks followed by repair through non-homologous end joining (NHEJ) or stalled fork repair. Furthermore, mutation of required NHEJ factor DNA Ligase 4 results in enhanced haploid recovery. Lastly, heritability and stability of a rearranged chromosome suggest a potential for enduring genomic novelty. These findings provide a tractable, natural system towards investigating the causes and mechanisms of complex genomic rearrangements similar to those associated with several human disorders.DOI: http://dx.doi.org/10.7554/eLife.06516.001

Brassica juncea Lines with Substituted Chimeric GFP-CENH3 Give Haploid and Aneuploid Progenies on Crossing with Other Lines

“…Progenies of the cross (HI X WT) of A. thaliana also yield high frequency of aneuploids along with haploids (Ravi and Chan, 2010). Besides, several structural chromosomal rearrangements giving rise to novel phenotypes have been reported (Tan et al, 2015). Thus, with regard to aneuploids, our results are in agreement with Ravi and Chan (2010) but differ from Kelliher et al (2016) who found no aneuploids in CENH3-based HI lines of maize.…”

Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis

“…Similar mechanisms of chromosome shattering and re-ligation also appear to be present in genetic plant [38] and fission yeast [39] models of chromosome missegregation. In Arabidopsis models, apparent micronuclei have been reported to produce complex rearrangements [38] that are strikingly similar to chromothripsis observed in human cancer genomes, implicating chromothripsis as a potentially conserved consequence of mitotic errors across evolution.…”

“…In Arabidopsis models, apparent micronuclei have been reported to produce complex rearrangements [38] that are strikingly similar to chromothripsis observed in human cancer genomes, implicating chromothripsis as a potentially conserved consequence of mitotic errors across evolution. Interestingly and along similar lines, protozoan ciliates such as Tetrahymena carry both a macronucleus and a micronucleus, the latter containing germline chromosomes that undergo deliberate DNA fragmentation and extensive rearrangements for subsequent conversion into the macronucleus [40].…”

“…Indeed, suppressing classical non-homologous end joining (c-NHEJ) (Box 3) by depleting or inhibiting the activity of LIG4 or DNA-PKcs prevented micronuclei-derived fragments to undergo repair [26], evidence supporting that c-NHEJ is the predominant mechanism for reassembling chromosomal fragments. LIG4 also appears to be required for repairing missegregated chromosomes in genetic plant models [38]. Chromosomal translocations in human cells are mediated primarily through c-NHEJ, although murine cells appear to favor alt-EJ [53, 54].…”

“…Chromosomal translocations in human cells are mediated primarily through c-NHEJ, although murine cells appear to favor alt-EJ [53, 54]. Sequence analyses of the breakpoint junctions from chromothriptic tumors [10] and experimental models of chromothripsis [25, 38] has revealed that a large proportion of breakpoints (but not all, as discussed below) lack significant homology or microhomology – consistent with the repair signature of c-NHEJ.…”