Uncoupled evolution of the Polycomb system and deep origin of non-canonical PRC1.

Polycomb group proteins, as part of the Polycomb repressive complexes, are essential in gene repression through chromatin compaction by canonical PRC1, mono-ubiquitylation of histone H2A by non-canonical PRC1 and tri-methylation of histone H3K27 by PRC2. Despite prevalent models emphasizing tight functional coupling between PRC1 and PRC2, it remains unclear whether this paradigm indeed reflects the evolution and functioning of these complexes. Here, we conduct a comprehensive analysis of the presence or absence of cPRC1, nPRC1 and PRC2 across the entire eukaryotic tree of life, and find that both complexes were present in the Last Eukaryotic Common Ancestor (LECA). Strikingly, ~42% of organisms contain only PRC1 or PRC2, showing that their evolution since LECA is largely uncoupled. The identification of ncPRC1-defining subunits in unicellular relatives of animals and fungi suggests ncPRC1 originated before cPRC1, and we propose a scenario for the evolution of cPRC1 from ncPRC1. Together, our results suggest that crosstalk between these complexes is a secondary development in evolution.

FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics.

Joint DNA molecules are natural byproducts of DNA replication and repair. Persistent joint molecules give rise to ultrafine DNA bridges (UFBs) in mitosis, compromising sister chromatid separation. The DNA translocase PICH (ERCC6L) has a central role in UFB resolution. A genome-wide loss-of-function screen is performed to identify the genetic context of PICH dependency. In addition to genes involved in DNA condensation, centromere stability, and DNA-damage repair, we identify FIGNL1-interacting regulator of recombination and mitosis (FIRRM), formerly known as C1orf112. We find that FIRRM interacts with and stabilizes the AAA+ ATPase FIGNL1. Inactivation of either FIRRM or FIGNL1 results in UFB formation, prolonged accumulation of RAD51 at nuclear foci, and impaired replication fork dynamics and consequently impairs genome maintenance. Combined, our data suggest that inactivation of FIRRM and FIGNL1 dysregulates RAD51 dynamics at replication forks, resulting in persistent DNA lesions and a dependency on PICH to preserve cell viability.

The rate of adaptive molecular evolution in wild and domesticated Saccharomyces cerevisiae populations.

Through its fermentative capacities, Saccharomyces cerevisiae was central in the development of civilisation during the Neolithic period, and the yeast remains of importance in industry and biotechnology, giving rise to bona fide domesticated populations. Here, we conduct a population genomic study of domesticated and wild populations of S. cerevisiae. Using coalescent analyses, we report that the effective population size of yeast populations decreased since the divergence with S. paradoxus. We fitted models of distributions of fitness effects to infer the rate of adaptive ( ω a $$ {\omega}_a $$ ) and non-adaptive ( ω na $$ {\omega}_{na} $$ ) non-synonymous substitutions in protein-coding genes. We report an overall limited contribution of positive selection to S. cerevisiae protein evolution, albeit with higher rates of adaptive evolution in wild compared to domesticated populations. Our analyses revealed the signature of background selection and possibly Hill-Robertson interference, as recombination was found to be negatively correlated with ω na $$ {\omega}_{na} $$ and positively correlated with ω a $$ {\omega}_a $$ . However, the effect of recombination on ω a $$ {\omega}_a $$ was found to be labile, as it is only apparent after removing the impact of codon usage bias on the synonymous site frequency spectrum and disappears if we control for the correlation with ω na $$ {\omega}_{na} $$ , suggesting that it could be an artefact of the decreasing population size. Furthermore, the rate of adaptive non-synonymous substitutions is significantly correlated with the residue solvent exposure, a relation that cannot be explained by the population's demography. Together, our results provide a detailed characterisation of adaptive mutations in protein-coding genes across S. cerevisiae populations.

There is another: H3K27me3-mediated genomic imprinting.

DNA methylation has long been considered the primary epigenetic mediator of genomic imprinting in mammals. Recent epigenetic profiling during early mouse development revealed the presence of domains of trimethylation of lysine 27 on histone H3 (H3K27me3) and chromatin compaction specifically at the maternally derived allele, independent of DNA methylation. Within these domains, genes are exclusively expressed from the paternally derived allele. This novel mechanism of noncanonical imprinting plays a key role in the development of mouse extraembryonic tissues and in the regulation of imprinted X-chromosome inactivation, highlighting the importance of parentally inherited epigenetic histone modifications. Here, we discuss the mechanisms underlying H3K27me3-mediated noncanonical imprinting in perspective of the dynamic chromatin landscape during early mouse development and explore evolutionary origins of noncanonical imprinting.

Whole slide imaging is a high-throughput method to assess Candida biofilm formation.

New strategies that enable fast and accurate visualization of Candida biofilms are necessary to better study their structure and response to antifungals agents. Here, we applied whole slide imaging (WSI) to study biofilm formation of Candida species. Three relevant biofilm-forming Candida species (C. albicans ATCC 10231, C. glabrata ATCC 2001, and C. tropicalis ATCC 750) were cultivated on glass coverslips both in presence and absence of widely used antifungals. Accumulated biofilms were stained with fluorescent markers and scanned in both bright-field and fluorescence modes using a WSI digital scanner. WSI enabled clear assessment of both size and structural features of Candida biofilms. Quantitative analyses readily detected reductions in biofilm-covered surface area upon antifungal exposure. Furthermore, we show that the overall biofilm growth can be adequately assessed across both bright-field and fluorescence modes. At the single-cell level, WSI proved adequate, as morphometric parameters evaluated with WSI did not differ significantly from those obtained with scanning electron microscopy, considered as golden standard at single-cell resolution. Thus, WSI allows for reliable visualization of Candida biofilms enabling both large-scale growth assessment and morphometric characterization of single-cell features, making it an important addition to the available microscopic toolset to image and analyse fungal biofilm growth.

Whole Slide Imaging and Its Applications to Histopathological Studies of Liver Disorders.

Histological analysis of hepatic tissue specimens is essential for evaluating the pathology of several liver disorders such as chronic liver diseases, hepatocellular carcinomas, liver steatosis, and infectious liver diseases. Manual examination of histological slides on the microscope is a classically used method to study these disorders. However, it is considered time-consuming, limited, and associated with intra- and inter-observer variability. Emerging technologies such as whole slide imaging (WSI), also termed virtual microscopy, have increasingly been used to improve the assessment of histological features with applications in both clinical and research laboratories. WSI enables the acquisition of the tissue morphology/pathology from glass slides and translates it into a digital form comparable to a conventional microscope, but with several advantages such as easy image accessibility and storage, portability, sharing, annotation, qualitative and quantitative image analysis, and use for educational purposes. WSI-generated images simultaneously provide high resolution and a wide field of observation that can cover the entire section, extending any single field of view. In this review, we summarize current knowledge on the application of WSI to histopathological analyses of liver disorders as well as to understand liver biology. We address how WSI may improve the assessment and quantification of multiple histological parameters in the liver, and help diagnose several hepatic conditions with important clinical implications. The WSI technical limitations are also discussed.