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Brach, G.

Publications and source records attributed to Brach, G..

3 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↗

Non-additive genetic components contribute significantly to population-wide gene expression variation

Gene expression variation, an essential step between genomic variation and phenotypic landscape, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence the heritability of expression traits remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originated from genetically divergent yeast isolates. We estimated the broad- and narrow-sense heritability across 5,087 transcript abundance traits and showed that non-additive components account for 36% of the phenotypic variance on average. By comparing allelic expression ratios in the hybrid and the corresponding parental pair, we identified regulatory changes in 25% of all cases, with a majority acting in trans. We further showed that trans-regulation could underlie coordinated expression variation across highly connected genes, resulting in significantly higher non-additive variance and most likely in some of the missing heritability of gene expression traits. HighlightsO_LIDiallel panel for dissecting genetic components underlying gene expression variation C_LIO_LINon-additive components account for 36% of gene expression trait heritability C_LIO_LIMost cis- regulatory variation is buffered by additional trans-acting variants C_LIO_LIGenes under trans- regulation show high non-additive variance and functional coherence C_LI

genetics↗

Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast

Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.

genomics↗