Biology subjects

Stocks, J.

Publications and source records attributed to Stocks, J..

7 recordsLinked to original sources

bioRxiv2026

CpG islands act as topological sinks for transcription-induced DNA supercoiling

Strong evolutionary selection has maintained CpG-dense islands (CGIs) at the promoters of constitutively expressed genes throughout the vertebrate genome, suggesting an important role in regulating DNA topology. Here, using Twist-seq, a psoralen-based approach for quantitative genome-wide profiling of DNA supercoiling, we reveal distinct topological states across human gene promoters. We show that CGI promoters accumulate elevated levels of negative supercoiling relative to non-CGI promoters and define localised topological domains at highly transcribed genes. Integrating genome-wide analyses with reaction-diffusion modelling and coarse-grained molecular dynamics simulations, we find that this behaviour is encoded by the intrinsic physical properties of CGI DNA. The GC-rich sequence context promotes nucleosome depletion and focuses torsional stress onto embedded AT-rich pockets, driving localised DNA melting and plectoneme-tip bubble formation within promoter-proximal nucleosome-free regions. This provides an energetically favourable pathway for redistributing transcription-induced torsional stress through transient strand separation and writhe, consistent with increased ssDNA formation at CGI promoters observed by ssDNA-seq. We propose that CGIs function as sequence-encoded topological sinks that buffer supercoiling while maintaining a promoter architecture permissive for transcription initiation, thereby preserving promoter integrity and genome stability.

molecular biology↗

bioRxiv2025

Recurrent evolution of cryptic triploids in cultivated enset increases yield

The high incidence of polyploidy in crops could be explained if domestication involved the selection of polyploids (cytotypes with more than two sets of chromosomes). Ancestral horticulture could have targeted desirable traits including yield, robustness to stress and to disease, rather than requiring knowledge of polyploidy itself. We find evidence for this process underway in enset (Ensete ventricosum, Musaceae) - a highly resilient crop constituting the main staple for over 20 million people in Ethiopia, which is clonally propagated and cultivated for its starch-rich corm and pseudostem. Prior to this study, enset was thought to be exclusively diploid (2n = 2x = 18). Using a newly-assembled chromosome-scale reference genome, and sequence data from 723 wild and domesticated enset individuals from southwestern Ethiopia, we demonstrate that around 20% of cultivated enset clones are triploid. We show that triploidy has arisen multiple times independently, that the triploid lineages have been given distinct landrace names, and planted disproportionately frequently. As well as providing evidence for enduring selection on triploids, our results reveal valuable genetic diversity captured by these triploid lines. They represent key resources for scientifically directed breeding of this major crop in the Ethiopian agrosystem, and could improve food security in sub-saharan Africa. Author SummaryDuplication of a species entire genome (polyploidization) plays an important part in evolution. Domestication may have favoured polyploid crops including wheat, coffee, potato, cotton, strawberry, and banana. It has been proposed that this trend is explained by the selection of advantageous traits exhibited by polyploids compared to their relatives with unduplicated genomes. These desirable traits include bigger fruits, seeds or other edible organs, and better tolerance to stress and disease. We unexpectedly find that a large proportion of cultivated enset lines have three copies of their genome (triploidy) instead of two (diploid). Enset is a highly resilient crop in the banana family; its stem and leaves are processed to provide one of the main food sources for over 20 million people in Ethiopia. Prior to our study, enset was thought to be exclusively diploid. Farmers use landrace names that distinguish diploids from triploids without having this new genetic information, showing the differences between them are recognised and given importance. Triploids were planted disproportionately and appear to grow faster, suggesting they are being selected for their higher productivity. These triploid ensets are an important genetic resource for scientifically directed breeding of new varieties, which could improve food security in sub-saharan Africa.

evolutionary biology↗

bioRxiv2024

Nuclear RNA forms an interconnected network of transcription-dependent and tunable microgels

Living cells are organised through active, non-equilibrium processes, yet the physical principles governing their material states remain unclear. The cell nucleus has been described as either fluid-like or solid-like, but these behaviours have not been reconciled within a single framework. Here we show that nascent RNA and the multivalent RNA-binding protein SAF-A assemble into a nucleus-spanning microgel network maintained near the sol-gel transition. This active network exhibits scale- and time-dependent viscoelasticity and naturally reconciles solid-like and fluid-like responses. By integrating super-resolution imaging with mechanistic polymer modelling, we identify RNA production and degradation as control parameters that tune network connectivity. The model predicts enhanced susceptibility to modest perturbations near criticality, which we confirm experimentally by shifting the system between sol-like and gel-like regimes. Measurements of molecular transport, combined with simulations, reveal size-dependent diffusion and transient trapping within gel pores, establishing direct physical consequences of the near-critical state. Our results identify RNA metabolism as an energy-driven regulator of nuclear material properties and position the nucleus as a living example of an active microgel poised near criticality.

molecular biology↗

bioRxiv2022

Genomic evidence of natural selection for ash dieback resistance

Rapid evolution via small shifts in allele frequencies at thousands of loci are a long- standing neo-Darwinian prediction but are hard to characterize in the wild. European ash tree (Fraxinus excelsior) populations have recently come under strong selection by the invasive fungal pathogen Hymenoscyphus fraxineus. Using genomic prediction models based on field trial phenotypes and 7,985 loci, we show a shift in genomically estimated breeding values in an ancient woodland, between adult trees established before the epidemic started and juvenile trees established since. Using simulations, we estimate that natural selection has eliminated 31% of the juvenile population. Thus, we document a highly polygenic heritable micro-evolutionary adaptive change over a single generation in the wild. One-Sentence SummarySubtle changes at thousands of genomic locations in one generation allow woodland trees to respond to a new selective pressure

evolutionary biology↗

bioRxiv2022

Introduced crops supplement rather than replace indigenous crops in an African center of agrobiodiversity

O_LICrop diversity plays a major role in underpinning food security. It is especially important to smallholder and subsistence farmers, who often rely on crop diversity for stable and resilient production. Despite this, global expansion of a small pool of major crops and the associated homogenisation of global agricultural systems may decrease on-farm crop diversity. C_LIO_LIWe surveyed 1,369 subsistence farms stratified across climate gradients in the Ethiopian Highlands, to characterise the richness and cultivated area of the 83 edible crops they contained. We further categorise these crops by their period of introduction to Ethiopia. We apply non-metric multidimensional scaling and mixed effects modelling to characterise agrisystem composition and test the impact of crop introductions. C_LIO_LIWe find a significant positive relationship between introduced and indigenous crop richness, suggesting that crop introductions have tended to supplement rather than replace or reduce indigenous crop diversity. Geographically matched farms with higher proportions of introduced crops, had significantly higher overall crop richness. Analysis of socio-economic drivers indicates that both poverty and low accessibility are associated with reduced cultivation of modern introductions. C_LIO_LIWe conclude that global patterns of major crop expansion do not necessarily result in agrobiodiversity loss for subsistence farmers, in our Ethiopian case study. Importantly, socioeconomic factors may strongly influence the farmers propensity to adopt novel species, suggesting targets for agricultural extension policies. Given the rapid climatic, economic and demographic changes impacting global food systems and the threats to food security these entail, robust indigenous agricultural systems supplemented with diverse introduced crops may enhance resilience. C_LI

ecology↗

bioRxiv2022

Investigating the temporal pattern of neuroimaging-based brain age estimation as a biomarker for Alzheimer's Disease related neurodegeneration

Neuroimaging-based brain-age estimation via machine learning has emerged as an important new approach for studying brain aging. The difference between ones estimated brain age and chronological age, the brain age gap (BAG), has been proposed as an Alzheimers Disease (AD) biomarker. However, most past studies on the BAG have been cross-sectional. Identifying how an individuals BAG temporal pattern changes over time would enable improved prediction of clinical outcome based on neurophysiological changes and better understanding of AD progression. To fill this gap, our study conducted predictive modeling using large neuroimaging data with up to 8 years of follow-up to examine the temporal patterns of the BAGs trajectory and how it varies by subject-level characteristics and disease status. To the best of our knowledge, this is the first effort to take a longitudinal approach to investigate the pattern and rate of change in BAG over time in individuals who progress from mild cognitive impairment (MCI) to clinical AD. Combining multimodal imaging data in a support vector regression model to estimate brain age yielded improved performance than single modality. Multilevel modeling results showed the BAG followed a linear increasing trajectory with a significantly faster rate in individuals with MCI who progressed to AD compared to cognitively normal or MCI individuals who did not progress. The dynamic changes in the BAG during AD progression were further moderated by gender and APO{varepsilon}4 carriership. Findings demonstrate the BAG as a potential biomarker for understanding individual specific temporal patterns related to AD progression.

neuroscience↗

bioRxiv2021

Genomic structure and diversity of oak populations in British Parklands

The two predominant oak species in Britain are Quercus robur (English or pedunculate oak) and Q. petraea (sessile oak). We sequenced the whole genomes of 386 oak trees from four British parkland sites and found over 50 million nuclear single nucleotide polymorphisms (SNPs), allowing us to identify 360 Q. robur, ten Q. petraea and 16 hybrid individuals using clustering methods. Comparing Q. robur and Q. petraea trees from Attingham Park, we found that the nuclear genomes of the two species are largely undifferentiated but identified 81 coding regions exhibiting strong interspecific differentiation. The nuclear genomes of our 360 Q. robur individuals showed no clear differentiation among the four parkland sites. Scans for selective sweeps in Q. robur highlighted regions containing genes with putative involvement in stress tolerance, one of which was moderately differentiated from Q. petraea. Reconstructions of past effective population sizes suggested a long population size decline in both Q. robur and Q. petraea over the Pleistocene, but population growth after the last glacial maximum. We assembled the whole chloroplast genomes of 287 Q. robur, 8 Q. petraea and 14 hybrid trees. In a phylogenetic network, these fell into five major haplotypes, which were shared among species but differed in frequency among parkland sites. We matched our chloroplast genome haplotypes to restriction enzyme fragment haplotypes identified in older studies that had surveyed ancient woodlands in Britain and much of Europe. This suggested that the parkland populations in our study derive from local seed sources.

genomics↗