Search bioRxiv⌕ Search

Biology subjects

Dutreux, F.

Publications and source records attributed to Dutreux, F..

6 recordsLinked to original sources

Recurrent loss of crossover interference punctuates the recombination landscape across yeast species

Meiotic recombination is essential for the accurate chromosome segregation and the generation of genetic diversity through crossover and gene conversion events. Although this process has been studied extensively in a few selected model species, understanding how its properties vary across species remains limited. In this context, we first characterized the meiotic recombination landscape and properties of the Kluyveromyces lactis budding yeast. We then conducted a comprehensive analysis of 28,897 recombination events spanning 567 meioses in five budding yeast species including Saccharomyces cerevisiae, Saccharomyces paradoxus, Lachancea kluyveri, Lachancea waltii and K. lactis. We observed variations in the recombination landscapes and properties across these species. The Saccharomyces yeasts displayed higher recombination rates compared to the non-Saccharomyces yeasts. In addition, bona fide crossover interference and associated crossover homeostasis were found in the Saccharomyces species only. The evolutionarily conserved ZMM pathway, essential for generating interference-dependent crossovers, has undergone multiple losses throughout evolution, suggesting variations in the regulation of crossover formation. Finally, recombination hotspots, although highly conserved within the Saccharomyces yeasts are not conserved beyond the Saccharomyces genus. Overall, these results highlight great variability and evolution in the recombination landscape between species.

genomics↗

Pan-transcriptome reveals a large accessory genome contribution to gene expression variation in yeast

Gene expression is an essential step in the translation of genotypes into phenotypes. However, little is known about the transcriptome architecture and the underlying genetic effects at a species-level. Here, we generated and analyzed the pan-transcriptome of [~]1,000 yeast natural isolates across 4,977 core and 1,468 accessory genes. We found that the accessory genome is an underappreciated driver of the transcriptome divergence. Global gene expression patterns combined with population structure show that the heritable expression variation mainly lies within subpopulation-specific signatures, for which the accessory genes are overrepresented. Genome-wide association analyses consistently highlight that the accessory genes are associated with proportionally more variants with larger effect sizes, illustrating the critical role of the accessory genome on the transcriptional landscape within and between populations.

genomics↗

142 telomere-to-telomere assemblies reveal the genome structural landscape in Saccharomyces cerevisiae

As population genomics is transitioning from single reference genomes to pangenomes, major improvements in terms of genome contiguity, phylogenetic sampling, haplotype phasing and structural variant (SV) calling are required. Here, we generated the Saccharomyces cerevisiae Reference Assembly Panel (ScRAP) comprising 142 reference-quality genomes from strains of various geographic and ecological origins that faithfully represent the genomic diversity and complexity of the species. The ca. 4,800 non-redundant SVs we identified impact the expression of genes near the breakpoints and contribute to gene repertoire evolution through disruptions, duplications, fusions and horizontal transfers. We discovered frequent cases of complex aneuploidies, preferentially involving large chromosomes that underwent large SVs. We also characterized the evolutionary dynamics of complex genomic regions that classically remain unassembled in short read-based projects, including the 5 Ty families and the 32 individual telomeres. Overall, the ScRAP represents a crucial step towards establishing a high-quality, unified and complete S. cerevisiae pangenome.

genomics↗

Loss of heterozygosity spectrum varies with ploidy levels in natural yeast populations

The appearance of genomic variations such as loss of heterozygosity (LOH) has a significant impact on phenotypic diversity observed in a population. Recent large-scale yeast population genomic surveys have shown a high frequency of these events in natural isolates and more particularly in polyploids. However, the frequency, extent, and spectrum of LOH in polyploid organisms have never been explored and is poorly characterized to date. Here, we accumulated 5,163 LOH events over 1,875 generations in 76 mutation accumulation (MA) lines comprising nine natural heterozygous diploid, triploid, and tetraploid natural S. cerevisiae isolates from different ecological and geographical origins. We found that the rate and spectrum of LOH are variable across ploidy levels. Of the total accumulated LOH events, 8.5%, 21%, and 70.5% of them were found in diploid, triploid, and tetraploid MA lines, respectively. Our results clearly shows that the frequency of generated LOH events increases with ploidy level. In fact, the cumulative LOH rates were estimated to be 9.3 x 10-3, 2.2 x 10-2, and 8.4 x 10-2 events per division for diploids, triploids, and tetraploids, respectively. In addition, a clear bias towards the accumulation of interstitial and short LOH tracts is observed in triploids and tetraploids compared to diploids. The variation of the frequency and spectrum of LOH events across ploidy level could be related to the genomic instability, characterizing higher ploidy isolates. Highlights- Yeast isolates with a high ploidy level (e.g., 3n and 4n) accumulate a larger number of LOH events compared to diploids. - The type of events and the LOH spectrum are both variable according to the ploidy levels. - A clear bias towards the accumulation of short LOH tracts is observed in polyploids compared to diploids. - The variation in LOH spectrum is most likely related to genomic instability present in higher ploidy strains.

genomics↗

Lessons from the meiotic recombination landscape of the ZMM deficient budding yeast Lachancea waltii

Meiotic recombination has been deeply characterized in a few model species only, notably in the budding yeast Saccharomyces cerevisiae. Interestingly, most members of the ZMM pathway that implements meiotic crossover interference in S. cerevisiae have been lost in Lachancea yeast species after the divergence of Lachancea kluyveri from the rest of the clade. This suggests major differences in the control of crossover distribution. After investigating meiosis in L. kluyveri, we determined the meiotic recombination landscape of Lachancea waltii and identified several characteristics that should help understand better the underlying mechanisms. Such characteristics include systematic regions of loss of heterozygosity (LOH) in L. waltii hybrids, compatible with dysregulated Spo11-mediated DNA double strand breaks (DSB) independently of meiosis. They include a higher recombination rate in L. waltii than in L. kluyveri despite the lack of multiple ZMM pro-crossover factors. L. waltii exhibits an elevated frequency of zero-crossover bivalents as L. kluyveri but opposite to S. cerevisiae. L. waltii gene conversion tracts lengths are comparable to those observed in S. cerevisiae and shorter than in L. kluyveri despite the lack of Mlh2, a factor limiting conversion tracts size in S. cerevisiae. L. waltii recombination hotspots are not shared with either S. cerevisiae or L. kluyveri, showing that meiotic recombination hotspots can evolve at a rather limited evolutionary scale within budding yeasts. Finally, in line with the loss of several ZMM genes, we found only residual crossover interference in L. waltii likely coming from the modest interference existing between recombination precursors. Significance statementStudying non-model species is relevant to understand better biological processes by shedding light on their evolutionary variations. Here we chose the non-model budding yeast Lachancea waltii to study meiotic recombination. In sexually reproducing organisms, meiotic recombination shuffles parental genetic combinations notably by crossovers that cluster in hotspots at the population level. We found remarkable variations compared to both the canonical Saccharomyces cerevisiae model and another close relative Lachancea kluyveri. Such variations notably include the loss in L. waltii of a layer of regulation of crossover distribution that is otherwise conserved in budding yeasts and mammals. They also include the lack of conservation of crossover hotspots across the Lachancea species while crossover hotspots are remarkably stable across the Saccharomyces species. Highlights- Extensive LOH events in L. waltii intraspecific hybrids - No conservation of the recombination hotspots across the Lachancea genus - Reduced but not suppressed crossover interference in the absence of the ZMM pathway - Similar gene conversion tract lengths in L. waltii, S. cerevisiae, and L. kluyveri despite the lack of MLH2 in L. waltii

genetics↗

Evolution of quantitative trait locus hotspots in yeast species

Dissecting the genetic basis of complex trait remains a real challenge. The budding yeast Saccharomyces cerevisiae has become a model organism for studying quantitative traits, successfully increasing our knowledge in many aspects. However, the exploration of the genotype-phenotype relationship in non-model yeast species could provide a deeper insight into the genetic basis of complex traits. Here, we have studied this relationship in the Lachancea waltii species which diverged from the S. cerevisiae lineage prior to the whole-genome duplication. By performing linkage mapping analyses in this species, we identified 86 quantitative trait loci (QTL) affecting growth fitness in a large number of conditions. The distribution of these loci across the genome has revealed two major QTL hotspots. A first hotspot corresponds to a general fitness QTL, impacting a wide range of conditions. By contrast, the second hotspot highlighted a fitness trade-off with a disadvantageous allele for drug-free conditions which proved to be advantageous in the presence of several drugs. Finally, the comparison of the detected QTL in L. waltii with those which had been previously identified for the same traits in a closely related species, Lachancea kluyveri, clearly revealed the absence of interspecific conservation of these loci. Altogether, our results expand our knowledge on the variation of the QTL landscape across different yeast species.

genetics↗