Biology subjects

Bendixsen, D.

Publications and source records attributed to Bendixsen, D..

3 recordsLinked to original sources

bioRxiv2026

Pervasive chromothripsis drives pleural mesothelioma to impact gene function and patient survival

Pleural mesothelioma (PM) is a tumour type showing high structural complexity but the full spectrum of variants present and their impacts are poorly understood. We comprehensively describe the mutational landscape of mesothelioma, exploiting a large (N=443) cohort profiling the tumour genome and transcriptome in parallel. We find that the majority of candidate driver variants are mediated by copy number alterations (CNAs) and discover high frequencies of complex rearrangements across most tumours, dominated by chromothripsis (74% of tumours) and chromoplexy (59%). Chromothripsis contributes to significant CNA hotspots to delete known PM tumour suppressor genes such as CDKN2A, NF2 and BAP1, thought to be among the earliest events in PM development; and the presence of chromothripsis is associated with significantly worse patient survival. We also discover multi-faceted crosstalk between the mitochondrial and nuclear genomes during PM evolution, involving alterations to both genomes, and mitochondrial expression changes associated with subtypes and chromothripsis.

cancer biology↗

bioRxiv2025

Commercial Saccharomyces cerevisiae baker's yeasts: strain redundancy, genome plasticity, and colonization of the sourdough environment and the human body

Leavening dough is one of the most widespread applications of fermentative yeast and the most common practice for the general public to come into contact with microbial cultures. Saccharomyces cerevisiae is the typical species used for dough making, but the evolutionary origin of strains isolated from dough is mixed. Here, using 49 newly sequenced and 183 previously described isolates from the bakery environment, we show that the traditional strains used in Europe for sourdough making are more closely related to Chinese Mantou sourdough lineages than to commercially used baker yeast strains. Surprisingly, the expansion of these traditional European strains into other human-associated niches, including the human body, has been very limited. This is in stark contrast to the Mixed-origin clade commercial baking yeasts, which consists of only a few globally distributed clonal lineages that dominate the yeast market and recurrently colonize sourdoughs and human hosts. These clonal lineages consistently maintain their ploidy, unique heterozygous chromosomal rearrangements, and stable aneuploidies in addition to several diverse structural variants. In addition to the previously known diploid and tetraploid groups of commercial isolates, we describe a widely distributed stable triploid aneuploid clonal lineage. We show that company practices and global trade help the distribution of these clonal clusters and that these yeasts are characterized by their exclusively mitotic reproduction.

microbiology↗

bioRxiv2019

Recombining your way out of trouble: The genetic architecture of hybrid fitness under environmental stress

Hybridization between species is a fundamental evolutionary force that can both promote and delay adaptation. There is a deficit in our understanding of the genetic basis of hybrid fitness, especially in non-domesticated organisms. We also know little about how hybrid fitness changes as a function of environmental stress. Here, we made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species, exposed populations to ten toxins, and sequenced the most resilient hybrids on low coverage using ddRADseq. We expected to find strong negative epistasis and heterozygote advantage in the hybrid genomes. We investigated three aspects of hybridness: 1) hybridity, 2) interspecific heterozygosity, and 3) epistasis (positive or negative associations between non-homologous chromosomes). Linear mixed effect models revealed strong genotype-by-environment interactions with many chromosomes and chromosomal interactions showing species-biased content depending on the environment. Against our predictions, we found extensive selection against heterozygosity such that homozygous allelic combinations from the same species were strongly overrepresented in an otherwise hybrid genomic background. We also observed multiple cases of positive epistasis between chromosomes from opposite species, confirmed by epistasis- and selection-free simulations, which is surprising given the large divergence of the parental species (~15% genome-wide). Together, these results suggest that stress-resilient hybrid genomes can be assembled from the best features of both parents, without paying high costs of negative epistasis across large evolutionary distances. Our findings illustrate the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of hybrid populations.

evolutionary biology↗