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Gorringe, N.

Publications and source records attributed to Gorringe, N..

4 recordsLinked to original sources

An atlas of eukaryotic centromere architecture reveals recurrent evolutionary dynamics

Centromeres evolved at the root of eukaryotes to segregate chromosomes during cell division. Despite their ancient origin, centromeric DNA sequences evolve rapidly and adopt diverse architectures, including point centromeres, satellite arrays, transposon clusters, and holocentrics. To analyse centromere evolution at a broad scale, we characterised architectures across 325 diverse Darwin Tree of Life genome assemblies. Centromere architecture is evolutionarily labile, and similar configurations arise independently across divergent lineages. In plants and animals, we modelled centromere evolution as a recurrent cycle, in which satellite- and transposon-based architectures interconvert, with independent origins of holocentricity. We curated >23 million satellite repeats comprising 263 families from 165 species. Despite sequence divergence between satellite families, higher order repeats are prevalent, indicating constraint on repeat architecture rather than primary sequence. Satellite arrays are heavily invaded by diverse transposon families, consistent with convergent adaptation to the centromeric niche. In 89 species, transposons themselves constitute the primary centromere structure. We observed centrophilic transposons forming tandem arrays, suggesting mechanisms for satellite regeneration. Our sample includes five independent origins of holocentricity in plants and animals, which vary in association with periodic satellite arrays. We propose that genetic instability, centrophilic transposition, and transmission distortion promote recurrent centromere architectural interconversions during evolution.

genomics↗

CRISPR-mediated centromere fission generates neo-chromosomes with distorted meiotic inheritance in Arabidopsis

Centromeres are essential for chromosome segregation and are epigenetically defined by CENH3/CENP-A nucleosomes. Centromere position along chromosomes varies within and between species, ranging from telocentric to metacentric architectures. Yet, how centromere position influences chromosome inheritance and karyotype evolution remains poorly understood. To reposition the centromere, we used CRISPR-Cas9 to break the centromeric satellite array of Arabidopsis thaliana chromosome 3. Fission chromosomes rapidly acquired telomeres, converting a metacentric into two stable telocentric neo-chromosomes. Neo-centromere formation involved genetic restructuring and de novo satellite higher-order repeat formation, together with epigenetic remodeling of CENH3 and DNA methylation. Crossing the six-chromosome fission line to five-chromosome wild type produced a meiosis-specific trivalent that mis-segregated and generated aneuploidy. Trivalent recombination doubled through two obligate crossovers, which were shifted towards the telomeres. Inheritance was strongly distorted in favor of the wild type centromere, as telocentrics segregated into inviable monosomic gametes. The reciprocal trisomic gametes were associated with centromere-proximal recombination, demonstrating that crossover position governs trivalent segregation. Distortion further increased when CENH3 was over-expressed, implicating centromere strength in the outcomes of trivalent meiosis. Our results reveal rapid centromere remodeling following karyotype change, and how trivalent centromere architecture distorts inheritance, with implications for hybrid incompatibility and synthetic chromosome design.

genetics↗

CRISPR targeting of H3K4me3 activates gene expression and unlocks centromeric crossover recombination in Arabidopsis

H3K4me3 is a fundamental and highly conserved chromatin mark across eukaryotes, playing a central role in many genome-related processes, including transcription, maintenance of cell identity, DNA damage repair, and meiotic recombination. However, identifying the causal function of H3K4me3 in these diverse pathways remains a challenge, and we lack the tools to manipulate it for agricultural benefit. Here we use the CRISPR-based SunTag system to direct H3K4me3 methyltransferases in the model plant, Arabidopsis thaliana. Targeting of SunTag-SDG2 activates the expression of the endogenous reporter gene, FWA. We show that SunTag-SDG2 can be employed to increase pathogen resistance by targeting the H3K4me3-dependent disease resistance gene, SNC1. Meiotic crossover recombination rates impose a limit on the speed with which new traits can be transferred to elite crop varieties. We demonstrate that targeting of SunTag-SDG2 to low recombining centromeric regions can significantly stimulate proximal crossover formation. Finally, we reveal that the effect is not specific to SDG2 and is likely dependent on the H3K4me3 mark itself, as the orthogonal mammalian-derived H3K4me3 methyltransferase, PRDM9, produces a similar effect on gene expression with reduced off-target potential. Overall, our study supports an instructive role for H3K4me3 in transcription and meiotic recombination and opens the door to precise modulation of important agricultural traits.

plant biology↗

Natural variation modifies centromere proximal meiotic crossover frequency and segregation distortion in Arabidopsis thaliana

BackgroundCentromeres mediate chromosome segregation during cell division. In plants, centromeres are loaded with CENH3-variant nucleosomes, which direct kinetochore formation and spindle microtubule interaction. Plant centromeres are frequently composed of megabase-scale satellite repeat arrays, or retrotransposon nests. In monocentric genomes, such as Arabidopsis thaliana, extended regions of pericentromeric heterochromatin surround the CENH3-occupied satellite arrays. A zone of suppressed meiotic crossover recombination contains the centromere and extends into the pericentromeres. Here, we explore how Arabidopsis natural genetic variation influences centromere-proximal crossover frequency, and segregation distortion through meiosis, when homologous centromeres are structurally heterozygous. ResultsWe used fluorescent crossover reporters to survey the effect of natural variation on centromere-proximal recombination in twelve F1 hybrids, capturing Arabidopsis Eurasian and relict diversity. The majority of F1 hybrids showed either elevated or suppressed centromere-proximal crossovers (49 of 60), relative to inbreds. We relate hybrid crossover frequencies to patterns of centromeric structural variation, and in a subset of accessions, to epigenetic patterns of CENH3 loading and DNA methylation. The fluorescent reporters also allow segregation distortion through meiosis to be compared between inbred and hybrid strains. We observed a minority of hybrids (18 of 60) with distorted segregation through meiosis compared to inbreds, with and without simultaneous change to centromere-proximal crossover frequency. ConclusionsWe reveal a complex relationship between centromere structural variation, epigenetic state, crossover recombination, and segregation distortion. We propose a model for how Arabidopsis centromere structural heterozygosity may cause segregation distortion during female meiosis.

genetics↗