Biology subjects

Fernandes, J. B.

Publications and source records attributed to Fernandes, J. B..

7 recordsLinked to original sources

bioRxiv2026

Bioelectrical phase transitions

Electrical signaling in biological systems is generally understood through the lens of single-channel biophysics, yet whether ensembles of ion channels can undergo cooperative opening and closing remains unclear. Here, we show that ensembles of voltage-gated ion channels can undergo bioelectrical order-disorder phase transitions driven by feedback between channel currents and local membrane voltage. When channels open, they carry ion-selective current that redistributes ions near the membrane and perturbs the transmembrane potential, thereby biasing the gating of nearby channels. This emergent nonequilibrium coupling generates a bona fide phase transition in ion channel ensembles. Finite-size analyses of the open-channel fraction, its fluctuations, and the distribution of collective channel states yield a voltage-temperature phase diagram with a first-order line separating collectively open and closed states and terminating at a critical point. The critical temperature is governed by a dimensionless conductance ratio set by ion transport, channel density, and confinement geometry. Applying this framework to measurements from the squid giant axon, the axon initial segment, and the nodes of Ranvier suggests that collective activation may be favored by high sodium-channel densities in large-diameter nerves, whereas the lower densities typical of potassium channels place them in an independent-gating regime.

biophysics↗

bioRxiv2026

MeiCOfi: Meiotic CrossOver Finder in haploid, diploid, polyploid and hyper-recombinant genomes

During the meiotic cell division, homologous chromosomes pair and recombine, leading to large reciprocal exchanges of genetic information. In most species, meiotic crossovers (COs) are crucial for normal chromosome segregation and they generate genetic diversity, which can be acted upon by natural selection in wild populations or by breeders to combine desirable traits in a genome. Identifying the position and frequency of COs is therefore essential in both classical genetics studies and breeding programmes. However, a computational tool capable of accurately detecting COs across diverse contexts, including varying marker densities, genome size and structure, recombination rate, and ploidy, remains lacking. We developed MeiCOfi (Meiotic CrossOver Finder) to detect meiotic crossover events at high-resolution from low-coverage genome sequencing data. We evaluated it using data from Arabidopsis thaliana, rice, barley and both intra- and inter-specific tomato hybrids, encompassing a wide range of genome complexities and marker densities. It reliably detects crossovers in hyper-recombinant A. thaliana with up to 62 CO per backcross offspring and in haploid gametes from barley with sequencing coverage as low as 0.1x. It can identify crossovers in polyploid genomes, including simulated recombinant tetraploids and also real data from tetraploid tomato hybrid offspring. Our results demonstrate that MeiCOfi can robustly identify crossovers in diverse genomic contexts.

bioinformatics↗

bioRxiv2025

Unlocking meiotic crossovers near plant centromeres

Crossovers (COs) ensure proper chromosome segregation during meiosis and generate genetic diversity. COs are non-uniformly distributed along chromosomes and almost universally suppressed in centromere-proximal regions, notably creating a significant bottleneck for plant breeding. The mechanism of this CO suppression is elusive, but chromatin state is a contributing factor. Here, we identify three factors that actively limit proximal CO in Arabidopsis, the cohesion establishment factor CTF18, the centromeric cohesin protector SGO2, and the deSUMOylase SPF2. The mutation of these factors allows both the formation of CO in centromere-proximal region where they were completely absent in the wild-type, and enhance their frequency where they were rare. COs can be further increased by combining these mutations together or with mutation in the DNA methylase CMT3, suggesting that multiple mechanism prevent proximal CO in parallel. The identification of the very conserved CTF18, SGO2 and SPF2 as suppressors of centromere-proximal CO highlights the importance of cohesin turnover in this process and opens up new possibilities for plant breeding.

genetics↗

bioRxiv2025

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↗

bioRxiv2024

MutLgamma enforces meiotic crossovers in Arabidopsis thaliana

During meiosis, each chromosome pair experiences at least one crossover (CO), which directs their balanced segregation in addition to shuffling genetic information. COs tend to be away from each other, a phenomenon known as CO interference. The main biochemical pathway for CO formation, which is conserved in distant eukaryotes, involves the ZMM proteins together with the MLH1-MLH3 complex (MutL{gamma}). Here, we aim to clarify the role of MutL{gamma} in CO formation in Arabidopsis thaliana. We show that AtMutL{gamma} is partially dispensable for ZMM-dependant CO formation. HEI10 large foci - that mark CO sites in wild-type-form at a normal level in mlh1 and mlh3 mutants, but are inefficiently maturated into COs. Mutating the MUS81 nuclease in either mlh1 or mlh3 leads to chromosome fragmentation, which is suppressed by further mutating the zmm msh5. This suggests that in the absence of MutL{gamma}, recombination intermediates produced by ZMMs are resolved by MUS81, which does not ensure CO formation. Finally, CO interference is not affected in mlh1, which is compatible with a random sub-sampling of normally patterned CO sites. We conclude that AtMutL{gamma} imposes designated recombination intermediates to be resolved exclusively as COs, supporting the view that MutL{gamma} asymmetrically resolves double-Holliday junctions, yielding COs.

genetics↗

bioRxiv2023

Structural variation and DNA methylation shape the centromere-proximal meiotic crossover landscape in Arabidopsis

BackgroundCentromeres load kinetochore complexes onto chromosomes, which mediate spindle attachment and allow segregation during cell division. Although centromeres perform a conserved cellular function, their underlying DNA sequences are highly divergent within and between species. Despite variability in DNA sequence, centromeres are also universally suppressed for meiotic crossover recombination, across eukaryotes. However, the genetic and epigenetic factors responsible for suppression of centromeric crossovers remain to be completely defined. ResultsTo explore the centromere-proximal recombination landscape, we mapped 14,397 crossovers against fully assembled Arabidopsis thaliana genomes. A. thaliana centromeres comprise megabase-scale satellite repeat arrays that load nucleosomes containing the CENH3 histone variant. Each chromosome possesses a structurally polymorphic 3-4 megabase region where crossovers were absent, that includes the satellite arrays, flanked by 1-2 megabase low-recombination zones. The recombination-suppressed regions are enriched for Gypsy/Ty3 retrotransposons, and additionally contain expressed genes with high genetic diversity that initiate meiotic recombination, yet do not crossover. We mapped crossovers at high-resolution in proximity to CEN3, which resolved punctate centromere-proximal hotspots that overlapped gene islands embedded in heterochromatin. Centromeres are densely DNA methylated and the recombination landscape was remodelled in DNA methylation mutants. We observed that the centromeric low-recombining zones decreased and increased crossovers in CG (met1) and non-CG (cmt3) mutants, respectively, whereas the core non recombining zones remained suppressed. ConclusionOur work relates the genetic and epigenetic organisation of the A. thaliana centromeres and flanking pericentromeric heterochromatin to the zones of crossover suppression that surround the CENH3-occupied satellite repeat arrays.

genomics↗

bioRxiv2017

Unleashing meiotic crossovers in hybrid plants

Meiotic crossovers shuffle parental genetic information, providing novel combinations of alleles on which natural or artificial selection can act. However, crossover events are relatively rare, typically one to three exchange points per chromosome pair. Recent work has identified three pathways limiting meiotic crossovers in Arabidopsis thaliana, that rely on the activity of FANCM1, RECQ42 and FIGL13, respectively. Here, we analyzed recombination in plants where one, two or three of these pathways were disrupted, in both pure line and hybrid contexts. The highest effect was observed when combining recq4 and figl1 mutations, which increased the hybrid genetic map length from 389 to 3037 centiMorgans. This corresponds to an unprecedented 7.8-fold increase in crossover frequency. Disrupting the three pathways do not further increases recombination, suggesting that some upper limit has been reached. The increase in crossovers is not uniform along chromosomes and rises from centromere to telomere. Finally, while in wild type recombination is much higher in male than in female meiosis (490 cM vs 290 cM), female recombination is higher than male in recq4 figl1 (3200 cM vs 2720 cM), suggesting that the factors that make wild-type female meiosis less recombinogenic than male wild-type meiosis do not apply in the mutant context. The massive increase of recombination observed in recq4 figl1 hybrids opens the possibility to manipulate recombination to enhance plant breeding efficiency.

genetics↗