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Biology subjects

Caron, T.

Publications and source records attributed to Caron, T..

5 recordsLinked to original sources

Generation of diversity in the blue cheese mold Penicillium roqueforti and identification of pleiotropic QTL for key cheese-making phenotypes

Elucidating the genomic architecture of quantitative traits is essential for our understanding of adaptation and for breeding in domesticated organisms. Penicillium roqueforti is the mold used worldwide for the blue cheese maturation, contributing to flavors through proteolytic and lipolytic activities. The two domesticated cheese populations display very little genetic diversity, but are differentiated and carry opposite mating types. We produced haploid F1 progenies from five crosses, using parents belonging to cheese and non-cheese populations. Analyses of high-quality genome assemblies of the parental strains revealed five large translocations, two having occurred via a circular intermediate. Offspring genotyping with genotype-by-sequencing (GBS) revealed several genomic regions with segregation distortion, possibly linked to degeneration in cheese lineages. We found transgressions for several traits relevant for cheese making, with offspring having more extreme trait values than parental strains. We identified quantitative trait loci (QTLs) for colony color, lipolysis, proteolysis, extrolite production, including mycotoxins, but not for growth rates. Some genomic regions appeared rich in QTLs for both lipid and protein metabolism, and other regions for the production of multiple extrolites, indicating that QTLs have pleiotropic impacts. Some QTLs corresponded to known biosynthetic gene clusters, e.g., for the production of melanin or extrolites. F1 hybrids constitute valuable strains for cheese producers, with new traits and genetic diversity, and allowed identifying target genomic regions for traits important in cheese making, paving the way for strain improvement. The findings further contribute to our understanding of the genetic mechanisms underlying rapid adaptation, revealing convergent adaptation targeting major regulators.

evolutionary biology↗

A new cheese population in Penicillium roqueforti and adaptation of the five populations to their ecological niche

Domestication is an excellent case study for understanding adaptation and multiple fungal lineages have been domesticated for fermenting food products. Studying domestication in fungi has thus both fundamental and applied interest. Genomic studies have revealed the existence of four populations within the blue-cheese-making fungus Penicillium roqueforti. The two cheese populations show footprints of domestication, but the adaptation of the two non-cheese populations to their ecological niches (i.e. silage/spoiled food and lumber/spoiled food) has not been investigated yet. Here, we reveal the existence of a new P. roqueforti population, specific to French Termignon cheeses, produced using small-scale traditional practices, with spontaneous blue mould colonisation. This Termignon population is genetically differentiated from the four previously identified populations, providing a novel source of genetic diversity for cheese making. Phenotypically, the non-Roquefort cheese population was the most differentiated, with specific traits beneficial for cheese making, in particular higher tolerance to salt, to acidic pH and to lactic acid. Our results support the view that this clonal population, used for many cheese types in multiple countries, is a domesticated lineage on which humans exerted strong selection. The Termignon population displayed substantial genetic diversity, both mating types, horizontally transferred regions previously detected in the non-Roquefort population, and intermediate phenotypes between cheese and non-cheese populations. The lumber/spoiled food and silage/spoiled food populations were not more tolerant to crop fungicides but showed faster growth in various carbon sources (e.g. dextrose, pectin, sucrose, xylose and/or lactose), which can be beneficial in their ecological niches. Such contrasted phenotypes between P. roqueforti populations, with beneficial traits for cheese-making in the cheese populations and enhanced ability to metabolise sugars in the lumber/spoiled food population, support the inference of domestication in cheese fungi and more generally of adaptation to anthropized environments.

microbiology↗

Prion protein lowering is a disease-modifying therapy across prion strains, disease stages, and endpoints

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that less than 25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease.

neuroscience↗

Strong effect of Penicillium roqueforti populations on volatile and metabolic compounds responsible for aromas, flavour and texture in blue cheeses

Studies of food microorganism domestication can provide important insight into adaptation mechanisms and lead to commercial applications. Penicillium roqueforti is a fungus with four genetically differentiated populations, two of which were independently domesticated for blue cheese-making, with the other two populations thriving in other environments. Most blue cheeses are made with strains from a single P. roqueforti population, whereas Roquefort cheeses are inoculated with strains from a second population. We made blue cheeses in accordance with the production specifications for Roquefort-type cheeses, inoculating each cheese with a single P. roqueforti strain, using a total of three strains from each of the four populations. We investigated differences between the cheeses made with the strains from the four P. roqueforti populations, in terms of the induced flora, the proportion of blue color, water activity and the identity and abundance of aqueous and organic metabolites as proxies for proteolysis and lipolysis as well as volatile compounds responsible for flavor and aroma. We found that the population-of-origin of the P. roqueforti strains used for inoculation had a minor impact on bacterial diversity and no effect on the abundance of the main microorganism. The cheeses produced with P. roqueforti strains from cheese populations had a higher percentage of blue area and a higher abundance of the volatile compounds typical of blue cheeses, such as methyl ketones and secondary alcohols. In particular, the Roquefort strains produced higher amounts of these aromatic compounds, partly due to more efficient proteolysis and lipolysis. The Roquefort strains also led to cheeses with a lower water availability, an important feature for preventing spoilage in blue cheeses, which is subject to controls for the sale of Roquefort cheese. The typical appearance and flavors of blue cheeses thus result from human selection on P. roqueforti, leading to the acquisition of specific features by the two cheese populations. These findings have important implications for our understanding of adaptation and domestication, and for cheese improvement.

evolutionary biology↗

Differential retention of transposable element-derived sequences in outcrossing Arabidopsis genomes

Transposable elements (TEs) have initially been viewed as pure genomic parasites but are now recognized as central genome architects and powerful agents of rapid adaptation. A proper evaluation of their evolutionary significance has been hampered by the paucity of short scale phylogenetic comparisons between closely related species. Here, we characterized the dynamics of TE accumulation at the micro-evolutionary scale by comparing two closely related plant species, Arabidopsis lyrata and A. halleri. Joint genome annotation in these two outcrossing species confirmed that both contain two distinct populations of TEs with either recent or old insertion histories. Identification of rare segregating insertions suggests that diverse TE families contribute to the ongoing dynamics of TE accumulation in the two species. TE fragments that have been maintained in both species, i.e. those that are orthologous, tend to be located on average closer to genes than those that are retained in one species only. Moreover, compared to non-orthologous TE insertions, those that are orthologous tend to produce fewer short interfering RNAs, are less heavily methylated when found within or adjacent to genes and these tend to have lower expression levels. These findings suggest that long-term retention of TE insertions reflects their frequent acquisition of adaptive roles and/or the deleterious effects of removing TE insertions when they are close to genes. Overall, our results indicate a rapid evolutionary dynamics of the TE landscape in these two outcrossing species, with an important input of a diverse set of new insertions with variable propensity to resist deletion.

evolutionary biology↗