12 research outputs found
Ethanol exposure increases mutation rate through error-prone polymerases
International audienceEthanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes
Spatial and Temporal Patterns of Genetic Diversity and Structure in Danish Populations of the Alcon Blue Butterfly <i>Phengaris alcon</i> (Denis & SchiffermĂĽller)
Phengaris alcon is an endangered, ant-associated butterfly found, amongst other places, in Denmark, where it has undergone a severe decline during the last century. However, the population genetic consequences of this decline remain unknown. To explore past and current patterns in population structure in relation to the decline, we analyzed DNA microsatellite data from 184 recent and 272 historical P. alcon specimens from 44 spatiotemporal locations in Denmark. We thus generated the most temporally and spatially comprehensive population genetic dataset for P. alcon in Denmark so far. Our results for the Bayesian population assignment of recent samples revealed three major current genetic clusters: western Jutland, northern Jutland, and the island of Læsø. Estimates of genetic diversity showed signs of inbreeding in several extant populations. When including data from museum specimens, only a single locatSion showed a decline in heterozygosity between 1967 and 2021. We suggest that the two distinct clusters in western and northern Jutland indicate two temporally separated Holocene colonizations of Denmark, the latter of which may have been aided by changes in agricultural practice in the late Neolithic period. The unique genetic signature of the Læsø populations may be a result of the admixture of northern Jutland and western Swedish populations
Ethanol exposure increases mutation rate through error-prone polymerases
Ethanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes.Voordeckers K, Colding C, Grasso L, Pardo B, Hoes L, Kominek J, Gielens K, Dekoster K, Gordon J, Van der Zande E, Bircham P, Swings T, Michiels J, Van Loo P, Nuyts S, Pasero P, Lisby M, Verstrepen KJ.Voordeckers K, et al. Among authors: nuyts s. Nat Commun. 2020 Jul 21;11(1):3664. doi: 10.1038/s41467-020-17447-3.Nat Commun. 2020. PMID: 32694532status: publishe
Dynamics and stabilization of the human gut microbiome during the first year of life
SummaryThe gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life
Correction: Amendments: Author Correction: A catalog of the mouse gut metagenome
International audienc