Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.05.05.078626

Chromosomal arrangement of synthetic lethal gene pairs: repulsion or attraction?

Hosseini, S.-R.·Wadie, B.·Petsalaki, E.
View original source ↗Export metadata ↓

Abstract

Synthetic lethal interactions are of paramount importance both in biology and in medicine, and hence increasing efforts have been devoted to their systematic identification. Our previous computational analysis revealed that in prokaryotic species, synthetic lethal genes tend to be further away in chromosomes than random (i.e. repulsion), which was shown to provide bacterial genomes with greater robustness to large-scale DNA deletions. To test the generalizability of this observation in eukaryotic genomes, we leveraged the wealth of experimentally determined synthetic lethal genetic interactions of yeast that are curated in the BioGRID (Biological General Repository for Interaction Datasets) database. We observed an opposite trend that is the genomic proximity of synthetic lethal gene pairs both on the 2D and 3D chromosomal space of the yeast genome (i.e. 2D and 3D attraction). To gain mechanistic insights into the origin of the attraction of synthetic lethal gene pairs in S. cerevisiae, we characterized four classes of genes, in which synthetic lethal interactions are enriched and partly explain the observed patterns of genomic attraction: i) gene pairs operating on the same pathways, 2) co-expressed genes, 3) gene pairs whose protein products physically interact and 4) the paralogs. However, our analysis revealed that the contribution of these four types of genes is not sufficient to fully explain the observed 2D and 3D attraction of synthetic lethal gene pairs and hence its evolutionary origin still remains as an open question. Significance statementUnravelling the organizing principles underlying gene arrangements is one of the fundamental questions of research in evolutionary biology. One understudied aspect of this organization is the relative chromosomal arrangement of synthetic lethal gene pairs. In this study, by analyzing a wealth of synthetic lethality data in yeast, we provide evidence that synthetic lethal gene pairs tend to be attracted to each other both on 2D and 3D chromosomal space of the yeast genome. This observation is in sharp contrast with the repulsion of synthetic lethal (metabolic) gene pairs that we observed previously in bacterial genomes. Characterizing the evolutionary forces underlying this genomic pattern in yeast can open the door towards an evolutionary theory of genome organization in eukaryotes.

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hosseini, S.-R., Wadie, B., Petsalaki, E.. 2020-05-05. Chromosomal arrangement of synthetic lethal gene pairs: repulsion or attraction?. https://doi.org/10.1101/2020.05.05.078626

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Ocean current models predict spatial structure for coastal biodiversity

Genomic diversity provides the raw material through which all evolutionary processes occur. Accurately describing how environmental features affect patterns of diversity shows promise in predicting the resilience of populations and entire communities to dynamic environments and novel stressors. Identifying the contribution of purely neutral responses to environmental effects can be difficult, especially across large spatial ranges with many covarying environmental features. Using an individual-based model of larvae carried by ocean currents, we predict patterns of neutral genomic diversity in a passively dispersed coastal species, suggesting large geographic regions of relative homogeneity with ancestry determined by the nearest "upstream" population with limited larval input. The genomic identity that dominates each region sharply transitions at the next such interruption, generating hierarchical structure and violating assumptions of isolation-by-distance. We call these upstream populations "lineage source regions" (LSRs), and we find strong concordance between LSR model predictions and an empirical population genomic survey of a keystone salt marsh mussel (Geukensia demissa). We quantitatively validate model performance and goodness-of-fit, updating baseline predictions of genomic diversity patterns from the classic isolation-by-distance model to this LSR framework. This spatially explicit coastal ancestry model has potential for generalization across passive dispersing species.

evolutionary biology↗
bioRxiv2026

Shared landscape, divergent genomes: Comparative population genomics of co-occurring flora in an isolated Australian mountain range

Understanding how landscape heterogeneity shapes genomic variation is key to conserving biodiversity and evolutionary potential. Yet conservation genomics is typically conducted at the single species level, limiting our ability to identify shared genomic patterns or understand how co-occurring taxa differ in their response to common environmental gradients. We assessed spatial patterns of genomic variation and their associations with geographic and environmental features among populations of nine co-existing plant species with contrasting life-histories and ecological traits across Gariwerd, a threatened biodiversity hotspot in south-eastern Australia. All species exhibited weak overall genetic structure, although the magnitude and spatial distribution of differentiation varied among species. Despite this variation, broadly consistent spatial trends were apparent, with higher genomic divergence largely concentrated in central zones and higher genomic diversity localised in southern regions of the landscape. Significant associations between genetic differentiation and geographic distance were observed in three species, while another species showed associations with environmental distance. These findings demonstrate that coexisting species can show overlapping spatial patterns in genomic variation while differing markedly in their associations with geographic and environmental variation across the same landscape. This comparative approach provides a basis for spatial prioritisation and conservation planning, while highlighting the complex eco-evolutionary processes operating across heterogeneous landscapes.

evolutionary biology↗
bioRxiv2026

BryoCAD: Extending Plant DNA Foundation Models Beyond Flowering Plants

Bryophytes exhibit diverse genome architectures and gene repertoires, yet their functional interpretation remains constrained by incomplete genomic annotations and limited experimental resources. Although DNA foundation models offer promising solutions, their applicability to evolutionarily divergent bryophytes remains largely unexplored. Here, we introduce BryoCAD, a DNA language model developed through continued pre-training of the angiosperm-specific PlantCAD2 model on 17 bryophyte genomes spanning hornworts, liverworts, and mosses. Across three representative bryophyte genomes and four gene-boundary motif recovery tasks, BryoCAD-Small improved mean zero-shot accuracy from 45.7% to 57.0%, a 24.8% relative increase over PlantCAD2-Small, while the over 200-fold larger Evo2-20B achieved a mean accuracy of only 39.3%. Remarkably, BryoCAD-Small outperformed PlantCAD2-Large in 11 of 12 motif-recovery comparisons across the three bryophytes, highlighting the benefits of lineage-specific adaptation over model scaling alone. These improvements extended to all six tested algal species, increasing mean accuracy from 26.3% to 37.5%, although performance varied across ferns and gymnosperms. BryoCAD also enhanced gene structure annotation: replacing PlantCAD2-Small with BryoCAD-Small increased transcript-level F1 scores from 0.578 to 0.625 in Marchantia polymorpha and from 0.485 to 0.530 in Physcomitrium patens. Together, our findings demonstrate that lineage-specific continued pre-training enhances genomic sequence interpretation and gene annotation across bryophytes, providing a transferable framework for extending DNA foundation models to evolutionarily diverse, understudied plant lineages.

evolutionary biology↗