Biology subjects

D'Angiolo, M.

Publications and source records attributed to D'Angiolo, M..

4 recordsLinked to original sources

bioRxiv2025

The adaptive molecular landscape of reprogrammed telomeric sequences

Telomeric sequences vary across the tree of life and intimately co-evolve with telomere-binding protein complexes. However, the molecular mechanisms allowing organisms to adapt to new telomeric sequences are difficult to gauge from extant species. Here, we reprogrammed multiple yeast lines to human-like telomeric repeats to unveil their molecular and fitness response to novel telomeres. Initially, the exchange of telomere sequences resulted in genome instability, proteome remodelling and severe fitness decline. However, adaptive evolution experiments selected for repeated mutations that drove adaptation to the humanized telomeres. These consisted of the recurrent amplification of the telomere-binding protein TBF1, by complex aneuploidies, or in repeated mutations that attenuate the DNA damage response. Overall, our results outline a response that defines the adaptive molecular landscape to novel telomeric sequences.

evolutionary biology↗

bioRxiv2022

Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones

Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1000 S. cerevisiae strains enabled us to explore telomere DNA length variation at an unprecedented scale. Here, we developed a bioinformatic pipeline (YeaISTY) to estimate telomere DNA length from whole-genome-sequences and applied it to the sequenced 1011 S. cerevisiae collection. Our results revealed broad natural telomere DNA length variation among the isolates. Notably, telomere DNA length is shorter in those derived from wild rather than domesticated environments. Wild isolates are enriched in loss-of-function mutations in genes known to regulate telomere DNA length and the return of domesticated yeasts to a wild habitat coincides with shorter telomeres. Moreover, telomere DNA length variation is associated with mitochondrial metabolism, and this association is driven by wild strains. Overall, these findings suggest that budding yeasts telomere DNA length regulation might be shaped by ecological life-styles.

genomics↗

bioRxiv2020

Aborting meiosis overcomes hybrid sterility

Hybrids between species or diverged lineages contain fundamentally novel genetic combinations but an impaired meiosis often makes them evolutionary dead ends. Here, we explored to what extent and how an aborted meiosis followed by a return-to-growth (RTG) promotes recombination across a panel of 20 yeast diploid backgrounds with different genomic structures and levels of sterility. Genome analyses of 284 clones revealed that RTG promoted recombination and generated extensive regions of loss-of-heterozygosity in sterile hybrids with either a defective meiosis or a heavily rearranged karyotype, whereas RTG recombination was reduced by high sequence divergence between parental subgenomes. The RTG recombination preferentially occurred in regions with local sequence homology and in meiotic recombination hotspots. The loss-of-heterozygosity had a profound impact on sexual and asexual fitness, and enabled genetic mapping of phenotypic differences in sterile lineages where linkage or association analyses failed. We propose that RTG gives sterile hybrids access to a natural route for genome recombination and adaptation. One sentence summaryAborting meiosis followed by a return to mitotic growth promotes evolution by genome wide-recombination in sterile yeast hybrids.

genetics↗

bioRxiv2018

Accurate tracking of the mutational landscape of diploid hybrid genomes reveals genetic background effects

BackgroundGenome evolution promotes diversity within a population via mutations, recombination, and whole-genome duplication. However, quantifying precisely these factors in diploid hybrid genomes is challenging. Here we present an integrated experimental and computational workflow to accurately track the mutational landscape of yeast diploid hybrids (MuLoYDH) in terms of single-nucleotide variants, small insertions/deletions, copy-number variants and loss-of-heterozygosity. ResultsHaploid Saccharomyces parents were combined into diploid hybrids with fully phased genome and controlled levels of heterozygosity. The resulting hybrids represented the ancestral state and were evolved under different laboratory protocols. Variant simulations enabled to efficiently integrate competitive and standard mapping, depending on local levels of heterozygosity and read length. Experimental validations proved high accuracy and resolution of our computational approach. Finally, applying MuLoYDH to four different diploids revealed striking genetic background effects. Homozygous S. cerevisiae showed ~4-fold higher mutation rate compared to S. paradoxus. In contrast, interspecies hybrids exhibited mutation rates similar to intraspecies hybrids despite 10-fold higher heterozygosity. MuLoYDH unveiled that a substantial fraction of the genome (~200 bp per generation) was shaped by loss-of-heterozygosity and this process was strongly inhibited by high levels of heterozygosity. ConclusionsWe report a comprehensive framework for characterizing the mutational spectrum of yeast diploid hybrids with unprecedented resolution, which can be generalised to other genetic systems. Applying MuLoYDH to laboratory-evolved hybrids provided novel quantitative insights into the evolutionary processes that mould yeast genomes.

genomics↗