bioRxiv Science⌕ Search

Biology subjects

Saayman, X.

Publications and source records attributed to Saayman, X..

3 recordsLinked to original sources

Response to divergent selection on meiotic recombination in Saccharomyces cerevisiae

Meiotic recombination is a key driver of evolution in sexually reproducing species, reshaping genetic diversity by generating novel allelic combinations. The rate of recombination varies substantially across living organisms depending on cis- or trans-acting genetic elements, as seen in many species, including the yeast Saccharomyces cerevisiae. Here, we report on an experimental evolution-based study to better understand the factors shaping this natural variation. Starting with a genetically diverse population of S. cerevisiae, we have carried out recurrent divergent selection on recombination rate using a fluorescence-based sorting approach in four independent lineages. After ten generations, we observed an average response of recombination rate of +28% after positive selection and -24% after negative selection, within the interval used for selection. In the adjacent region, however, we observed a weaker response in the opposite direction, and no response in four other unlinked genomic regions. Whole-genome sequencing of individuals selected for high recombination revealed mixed outcomes in the four independently evolved lineages for high genome-wide recombination rates. However, all four lineages showed selection for high recombination locally, with particular haplotypes heavily favored and sequence- or structural variation-based heterozygosity selected against within the selection interval. Overall, this experimental evolution approach provides original and useful insights into the evolvability of the meiotic recombination rate and the associated genetic determinants.

genetics↗

Assessing the molecular and phenotypic contribution of a horizontally acquired region to yeast adaptation

Horizontal Gene Transfer (HGT) is the movement of genetic material across species. In Saccharomyces cerevisiae, a DNA segment known as Region B was acquired horizontally from a distant yeast species. This region ([~]17 Kb) encodes 5 genes and is present in the genomes of yeast strains from different phylogenetic clades, with its contribution to yeast niche-specific adaptation remaining unclear. In this work, the genomic structure of Region B was analyzed in yeast strains from the ScRAP (Saccharomyces cerevisiae Reference Assembly Panel) collection, identifying 10 variants that maintain a circular continuity. To assess the role of Region B in yeast adaptation, we performed a high-throughput phenotyping of the ScRAP collection under different growth conditions, identifying that Region B is potentially associated with higher tolerance to oxidative stress. Then, we selected a single yeast strain from the ScRAP collection for characterization of the transcriptional activity of each gene within Region B using a fluorescent reporter. The results revealed that gene expression depends on the hosts genetic background and transcription factors encoded within Region B. To identify the genetic determinants involved in Region B expression within different genetic backgrounds, three expression Quantitative Trait Loci (eQTLs) were mapped and validated. Finally, by performing Region B deletion, we determine the contribution of this region to different fermentative phenotypes, including fermentation rate and amino acid consumption. Altogether, our results suggest a complex regulatory interaction between the horizontally acquired genes and the host genome that contributes to yeast adaptation under fermentation conditions.

molecular biology↗

The RAD51 recombinase protects mitotic chromatin in human cells

The RAD51 recombinase plays critical roles in safeguarding genome integrity, which is fundamentally important for all living cells. While interphase functions of RAD51 in repairing broken DNA and protecting stalled replication forks are well characterised, its role in mitosis remains contentious. In this study, we show that RAD51 protects under-replicated DNA in mitotic human cells and, in this way, promotes mitotic DNA synthesis (MiDAS) and successful chromosome segregation. MiDAS was globally detectable irrespective of DNA damage and was promoted by de novo RAD51 recruitment, RAD51-mediated fork protection, and RAD51 phosphorylation by the key mitotic regulator Polo-like kinase 1. Importantly, acute inhibition of RAD51-promoted MiDAS led to mitotic DNA damage, delayed anaphase onset and induced centromere fragility, revealing a mechanism that prevents the satisfaction of the spindle assembly checkpoint when chromosomal replication remains incomplete. This study hence identifies an unexpected function of RAD51 in promoting the stability of mitotic chromatin.

molecular biology↗