Biology subjects

Lannes, R.

Publications and source records attributed to Lannes, R..

4 recordsLinked to original sources

bioRxiv2025

Defective splicing of Y-chromosome-linked gigantic genes underlies hybrid male sterility in Drosophila

The Y chromosome evolves rapidly, often differing dramatically even between closely related species. While such divergence has long been suspected to contribute to hybrid male sterility, leading to reproductive isolation and thus speciation, the underlying mechanisms remain elusive. Here, we identify a molecular basis linking Y chromosome divergence to reproductive isolation in Drosophila. We show that male hybrids between D. simulans and D. mauritiana fail to properly express key Y-linked fertility genes. These genes contain unusually large introns, exceeding megabases and show substantial sequence divergence between species. In the hybrids, these gigantic introns are misprocessed, resulting in widespread splicing defects, including aberrant "back-splicing" events that join later exons to earlier ones. Our findings suggest that sequence divergence within introns can disrupt essential gene expression through defective splicing, providing a mechanistic link between rapid Y chromosome evolution and hybrid sterility. This work highlights the underappreciated role of intronic divergence in speciation.

evolutionary biology↗

bioRxiv2025

OmniSplice: a framework-free splicing event reporter

Splicing generates mature mRNA by removing introns from nascent transcripts and is widely studied using RNA sequencing. However, most RNA-seq analysis pipelines classify RNA-seq reads according to predefined splice-junction structures and discard those that do not conform to such predefined models, potentially obscuring biologically meaningful splicing events. In this study, we developed OmniSplice, a computational framework that captures and analyzes RNA-seq reads that overlap annotated exon ends without assuming predefined splicing architectures. This approach enables systematic detection of non-canonical splicing events that are often overlooked by conventional analyses. Applying OmniSplice to Drosophila splicing factor mutants and mouse TDP-43 mutant datasets, we found widespread splicing defects with non-canonical junctions that were not previously recognized, including back-splicing and trans-splicing. Together, these results demonstrate that RNA-seq datasets may contain a substantial reservoir of overlooked splicing information, warranting more comprehensive approaches for analyzing RNA-seq data for splicing events.

bioinformatics↗

bioRxiv2024

Co-transcriptional splicing facilitates transcription of gigantic genes

Although introns are typically tens to thousands of nucleotides, there are notable exceptions. In flies as well as humans, a small number of genes contain introns that are more than 1000 times larger than typical introns, exceeding hundreds of kilobases (kb) to megabases (Mb). It remains unknown why gigantic introns exist and how cells overcome the challenges associated with their transcription and RNA processing. The Drosophila Y chromosome contains some of the largest genes identified to date: multiple genes exceed 4Mb, with introns accounting for over 99% of the gene span. Here we demonstrate that co-transcriptional splicing of these gigantic Y-linked genes is important to ensure successful transcription: perturbation of splicing led to the attenuation of transcription, leading to a failure to produce mature mRNA. Cytologically, defective splicing of the Y-linked gigantic genes resulted in disorganization of transcripts within the nucleus suggestive of entanglement of transcripts, likely resulting from unspliced long RNAs. We propose that co-transcriptional splicing maintains the length of nascent transcripts of gigantic genes under a critical threshold, preventing their entanglement and ensuring proper gene expression. Our study reveals a novel biological significance of co-transcriptional splicing.

developmental biology↗

bioRxiv2024

Network studies unveil new groups of highly divergent proteins in families as old as cellular life with important biological functions in the ocean

BackgroundMetagenomics has considerably broadened our knowledge of microbial diversity, unravelling fascinating adaptations and characterising multiple novel major taxonomic groups, e.g. CPR bacteria, DPANN and Asgard archaea, and novel viruses. Such findings profoundly reshaped the structure of the known tree of life and emphasised the central role of investigating uncultured organisms. However, despite significant progresses, a large portion of proteins predicted from metagenomes remain today unannotated, both taxonomically and functionally, across many biomes and in particular in oceanic waters, including at relatively lenient clustering thresholds. ResultsHere, we used an iterative, network-based approach for remote homology detection, to probe a dataset of 40 million ORFs predicted in marine environments. We assessed the environmental diversity of 53 gene families as old as cellular life, broadly distributed across the Tree of Life. About half of them harboured clusters of environmental homologues that diverged significantly from the known diversity of published complete genomes, with representatives distributed across all the oceans. In particular, we report the detection of environmental clades with new structural variants of essential genes (SMC), divergent polymerase subunits forming deep-branching clades in the polymerase tree, and variant DNA recombinases of unknown origin in the ultra-small size fraction. ConclusionsThese results indicate that significant environmental diversity may yet be unravelled even in strongly conserved gene families. Protein sequence similarity network approaches, in particular, appear well-suited to highlight potential sources of biological novelty and make better sense of microbial dark matter across taxonomical scales.

evolutionary biology↗